Materiały źródłowe

• #1 Niemann-Pick disease: MedlinePlus Medical EncyclopediaLock

  https://medlineplus.gov/ency/article/001207.htm

  Symptoms vary. Other health conditions may cause similar symptoms. The early stages of the disease may only cause a few symptoms. A person may never have all the symptoms. […] Type A usually begins in the first few months of life. Symptoms may include: Abdominal (belly area) swelling by 3 to 6 months of age, Cherry red spot at the back of the eye (on the retina), Feeding difficulties, Loss of early motor skills (gets worse over time). […] Type B symptoms are usually milder. They occur in late childhood or the teenage years. Abdominal swelling may occur in young children. There is almost no brain and nervous system involvement, such as loss of motor skills. Some children may have repeated respiratory infections. […] Types C and C1 usually affects school-age children. However, it may occur any time between early infancy to adulthood. Symptoms may include: Difficulty moving limbs that may lead to unsteady gait, clumsiness, walking problems, Enlarged spleen, Enlarged liver, Jaundice at (or shortly after) birth, Learning difficulties and intellectual decline, Seizures, Slurred, irregular speech, Sudden loss of muscle tone that may lead to falls, Tremors, Trouble moving the eyes up and down.

• #2 Niemann-Pick disease: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/niemann-pick-disease/

  Niemann-Pick disease is a condition that affects many body systems. It has a wide range of symptoms that vary in severity. […] Infants with Niemann-Pick disease type A usually develop an enlarged liver and spleen (hepatosplenomegaly) by age 3 months and fail to gain weight and grow at the expected rate (failure to thrive). The affected children develop normally until around age 1 year when they experience a progressive loss of mental abilities and movement (psychomotor regression). Children with Niemann-Pick disease type A also develop widespread lung damage (interstitial lung disease) that can cause recurrent lung infections and eventually lead to respiratory failure. All affected children have an eye abnormality called a cherry-red spot, which can be identified with an eye examination. Children with Niemann-Pick disease type A generally do not survive past early childhood.

• #3 Niemann-Pick disease type C | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-5-16

  The age of onset of the systemic symptoms is not related with that of the neurological disease (the latter can occur many years or even decades later), while there is a correlation between the age of onset of the neurological symptoms and the general further course of the disease and lifespan. […] Patients with the severe neurologic early infantile form often die between 3 and 5 years of age, those with a late-infantile neurologic onset usually between 7 and 12. Patients with a juvenile neurologic onset survive until adolescence or later, with a sizable proportion reaching the age of 30. In a review of 68 cases with adult onset, the mean age at death (on 20 patients) was 38 10.2 years, but some patients have reached the age of 70.

• #4 Niemann-Pick disease Information | Mount Sinai – New York

  https://www.mountsinai.org/health-library/diseases-conditions/niemann-pick-disease

  Niemann-Pick disease (NPD) is a group of diseases passed down through families (inherited) in which fatty substances called lipids collect in the cells of the spleen, liver, and brain. […] Each one can cause different symptoms and may occur at different times throughout life. […] Symptoms vary. Other health conditions may cause similar symptoms. The early stages of the disease may only cause a few symptoms. A person may never have all the symptoms. […] Type A usually begins in the first few months of life. Symptoms may include: Abdominal (belly area) swelling by 3 to 6 months of age, Cherry red spot at the back of the eye (on the retina), Feeding difficulties, Loss of early motor skills (gets worse over time). […] Type B symptoms are usually milder. They occur in late childhood or the teenage years. Abdominal swelling may occur in young children. There is almost no brain and nervous system involvement, such as loss of motor skills. Some children may have repeated respiratory infections.

• #5 Niemann-Pick Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK556129/

  Nieman-Pick disease (NPD) type A presents in the first few months of life, usually before three months of age, as hepatosplenomegaly and growth retardation. By the age of one year, neurological symptoms appear as psychomotor retardation and regression of developmental milestones. All patients with NPD type A have a classical eye finding called cherry-red spot. These children usually do not survive past early childhood. NPD type B presents in mid-childhood and is not as severe as type A. These patients have hepatosplenomegaly, interstitial lung disease (ILD), causing recurrent lung infections, thrombocytopenia, and slowed bone growth. About one-third of patients with type B NPD have the cherry-red spot and neurological symptoms. NPD type C can present at any age but usually affects children. Affected individuals can have ataxia, dystonia, supranuclear gaze palsy (SNGP), dysphonia, dysphagia, and severe liver and lung disease.

• #6 Sphingomyelinase Deficiency Clinical Presentation: History, Physical Examination

  https://emedicine.medscape.com/article/951564-clinical

  The clinical presentation and course of NPD type A is relatively uniform and is characterized by normal appearance at birth. Some patients may have neonatal edema, and hydrops fetalis may occur. The first sign detected is usually the presence of hepatosplenomegaly, which is evident at age 3 months and becomes progressively greater. The liver is usually enlarged out of proportion to the spleen. […] The patient’s development seems to progress normally until about age 6 months, followed by a plateau phase from 6 months until about age 15 months. Lastly, rapidly progressive psychomotor and intellectual deterioration occur. Psychomotor development does not progress beyond the 12-month level, and in later stages, the affected child is completely unable to interact with his/her environment. […] Mild hypotonia may be evident by age 6 months, followed by progressive loss of tone and deep tendon reflexes. With disease progression, loss of motor function occurs, and in the final stages, spasticity and rigidity are evident.

• #7 Niemann-Pick disease: MedlinePlus Medical EncyclopediaLock

  https://medlineplus.gov/ency/article/001207.htm

  Symptoms vary. Other health conditions may cause similar symptoms. The early stages of the disease may only cause a few symptoms. A person may never have all the symptoms. […] Type A usually begins in the first few months of life. Symptoms may include: Abdominal (belly area) swelling by 3 to 6 months of age, Cherry red spot at the back of the eye (on the retina), Feeding difficulties, Loss of early motor skills (gets worse over time). […] Type B symptoms are usually milder. They occur in late childhood or the teenage years. Abdominal swelling may occur in young children. There is almost no brain and nervous system involvement, such as loss of motor skills. Some children may have repeated respiratory infections. […] Types C and C1 usually affects school-age children. However, it may occur any time between early infancy to adulthood. Symptoms may include: Difficulty moving limbs that may lead to unsteady gait, clumsiness, walking problems, Enlarged spleen, Enlarged liver, Jaundice at (or shortly after) birth, Learning difficulties and intellectual decline, Seizures, Slurred, irregular speech, Sudden loss of muscle tone that may lead to falls, Tremors, Trouble moving the eyes up and down.

• #8 Niemann-Pick disease: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/niemann-pick-disease/

  Niemann-Pick disease is a condition that affects many body systems. It has a wide range of symptoms that vary in severity. […] Infants with Niemann-Pick disease type A usually develop an enlarged liver and spleen (hepatosplenomegaly) by age 3 months and fail to gain weight and grow at the expected rate (failure to thrive). The affected children develop normally until around age 1 year when they experience a progressive loss of mental abilities and movement (psychomotor regression). Children with Niemann-Pick disease type A also develop widespread lung damage (interstitial lung disease) that can cause recurrent lung infections and eventually lead to respiratory failure. All affected children have an eye abnormality called a cherry-red spot, which can be identified with an eye examination. Children with Niemann-Pick disease type A generally do not survive past early childhood.

• #9 Niemann-Pick Disease | Baby’s First Test | Newborn Screening | Baby Health

  https://babysfirsttest.org/newborn-screening/conditions/niemann-pick-disease

  Niemann-Pick disease type A (NPD-A), the more severe form of NPD, usually develops in the first few months of life and progress rapidly. Early signs of this form include: Abdominal swelling (due to enlarged liver and spleen), Poor growth, Poor weight gain, Feeding difficulties, Loss of motor skills, Diarrhea, Vomiting, Frequent lung infections, Developmental delay. […] In Niemann-Pick disease type B (NPD-B), symptoms are usually milder and do not develop until later in childhood or adolescence. Early signs of this form include: Abdominal swelling (due to enlarged liver and spleen), Frequent lung infections, Short stature, Low weight, Developmental delay. […] Unfortunately, babies with Niemann-Pick disease type A (NPD-A) have many life-threatening medical problems and usually do not survive past age three.

• #10 Niemann-Pick disease Information | Mount Sinai – New York

  https://www.mountsinai.org/health-library/diseases-conditions/niemann-pick-disease

  Niemann-Pick disease (NPD) is a group of diseases passed down through families (inherited) in which fatty substances called lipids collect in the cells of the spleen, liver, and brain. […] Each one can cause different symptoms and may occur at different times throughout life. […] Symptoms vary. Other health conditions may cause similar symptoms. The early stages of the disease may only cause a few symptoms. A person may never have all the symptoms. […] Type A usually begins in the first few months of life. Symptoms may include: Abdominal (belly area) swelling by 3 to 6 months of age, Cherry red spot at the back of the eye (on the retina), Feeding difficulties, Loss of early motor skills (gets worse over time). […] Type B symptoms are usually milder. They occur in late childhood or the teenage years. Abdominal swelling may occur in young children. There is almost no brain and nervous system involvement, such as loss of motor skills. Some children may have repeated respiratory infections.

• #11 Niemann-Pick Disease, Types A and B | Hereditary Ocular Diseases

  https://disorders.eyes.arizona.edu/disorders/niemann-pick-disease-types-and-b

  Affected infants usually develop prominent cherry red spots during the first 12 months of life and the entire retina has an opaque appearance. […] Vision in the first year of life is likely normal as infants have normal fixation, pupillary reactions, and following movements with no nystagmus. However, by about 2 years of age visual responsiveness may be lost. […] Both the age of onset of neurological symptoms and the rate of progression are highly variable. Type A, known as the infantile form, is the more severe disease with onset by 6 months of age with rapid progression and few patients survive beyond three years of age. […] Neonates seem to develop normally for the first 6 months but then become irritable, fail to thrive and feed poorly. Hepatosplenomegaly is usually the first physical sign. Hypotonia and pulmonary infections are common. These patients never achieve normal developmental milestones such as sitting, walking or crawling and the neurodegeneration is relentless from this point with the median age at death 21 months, usually from respiratory disease. […] The less severe form of Niemann-Pick disease, type B, has a later onset and slower course. Such patients have widespread visceral disease affecting liver, spleen and lungs with hyperlipidemia but few neurologic symptoms and often survive into adulthood.

• #12 Niemann-Pick disease: MedlinePlus Medical EncyclopediaLock

  https://medlineplus.gov/ency/article/001207.htm

  Symptoms vary. Other health conditions may cause similar symptoms. The early stages of the disease may only cause a few symptoms. A person may never have all the symptoms. […] Type A usually begins in the first few months of life. Symptoms may include: Abdominal (belly area) swelling by 3 to 6 months of age, Cherry red spot at the back of the eye (on the retina), Feeding difficulties, Loss of early motor skills (gets worse over time). […] Type B symptoms are usually milder. They occur in late childhood or the teenage years. Abdominal swelling may occur in young children. There is almost no brain and nervous system involvement, such as loss of motor skills. Some children may have repeated respiratory infections. […] Types C and C1 usually affects school-age children. However, it may occur any time between early infancy to adulthood. Symptoms may include: Difficulty moving limbs that may lead to unsteady gait, clumsiness, walking problems, Enlarged spleen, Enlarged liver, Jaundice at (or shortly after) birth, Learning difficulties and intellectual decline, Seizures, Slurred, irregular speech, Sudden loss of muscle tone that may lead to falls, Tremors, Trouble moving the eyes up and down.

• #13 Sphingomyelinase Deficiency Clinical Presentation: History, Physical Examination

  https://emedicine.medscape.com/article/951564-clinical

  The clinical presentation and course of NPD type A is relatively uniform and is characterized by normal appearance at birth. Some patients may have neonatal edema, and hydrops fetalis may occur. The first sign detected is usually the presence of hepatosplenomegaly, which is evident at age 3 months and becomes progressively greater. The liver is usually enlarged out of proportion to the spleen. […] The patient’s development seems to progress normally until about age 6 months, followed by a plateau phase from 6 months until about age 15 months. Lastly, rapidly progressive psychomotor and intellectual deterioration occur. Psychomotor development does not progress beyond the 12-month level, and in later stages, the affected child is completely unable to interact with his/her environment. […] Mild hypotonia may be evident by age 6 months, followed by progressive loss of tone and deep tendon reflexes. With disease progression, loss of motor function occurs, and in the final stages, spasticity and rigidity are evident.

• #14 Niemann-Pick Disease | Baby’s First Test | Newborn Screening | Baby Health

  https://babysfirsttest.org/newborn-screening/conditions/niemann-pick-disease

  Niemann-Pick disease type A (NPD-A), the more severe form of NPD, usually develops in the first few months of life and progress rapidly. Early signs of this form include: Abdominal swelling (due to enlarged liver and spleen), Poor growth, Poor weight gain, Feeding difficulties, Loss of motor skills, Diarrhea, Vomiting, Frequent lung infections, Developmental delay. […] In Niemann-Pick disease type B (NPD-B), symptoms are usually milder and do not develop until later in childhood or adolescence. Early signs of this form include: Abdominal swelling (due to enlarged liver and spleen), Frequent lung infections, Short stature, Low weight, Developmental delay. […] Unfortunately, babies with Niemann-Pick disease type A (NPD-A) have many life-threatening medical problems and usually do not survive past age three.

• #15 Niemann-Pick disease | Beacon Health System

  https://www.beaconhealthsystem.org/library/diseases-and-conditions/niemann-pick-disease?content_id=CON-20257402

  Type A the most severe form begins in infancy. Symptoms include a liver that becomes too large, severe brain damage and nerve loss that worsens over time. There is no cure. Most children do not live past a few years of age. […] Type B sometimes called juvenile-onset Niemann-Pick disease usually begins later in childhood. It does not involve damage to the brain. Symptoms include nerve pain, problems walking, vision problems, and a liver and spleen that become too large. Lung problems also can happen. Most people with type B live into adulthood. But liver and lung problems worsen over time. Some people have symptoms that overlap between types A and B. […] Niemann-Pick disease type C is caused by changes in the NPC1 and NPC2 genes. With these changes, the body doesn’t have the proteins it needs to move and use cholesterol and other lipids in cells. Cholesterol and other lipids build up in the cells of the liver, spleen or lungs. Over time, the nerves and brain also are affected. This causes problems with eye movements, walking, swallowing, hearing and thinking. Symptoms vary widely, can appear at any age and get worse over time.

• #16 Niemann-Pick disease: MedlinePlus Medical EncyclopediaLock

  https://medlineplus.gov/ency/article/001207.htm

  Symptoms vary. Other health conditions may cause similar symptoms. The early stages of the disease may only cause a few symptoms. A person may never have all the symptoms. […] Type A usually begins in the first few months of life. Symptoms may include: Abdominal (belly area) swelling by 3 to 6 months of age, Cherry red spot at the back of the eye (on the retina), Feeding difficulties, Loss of early motor skills (gets worse over time). […] Type B symptoms are usually milder. They occur in late childhood or the teenage years. Abdominal swelling may occur in young children. There is almost no brain and nervous system involvement, such as loss of motor skills. Some children may have repeated respiratory infections. […] Types C and C1 usually affects school-age children. However, it may occur any time between early infancy to adulthood. Symptoms may include: Difficulty moving limbs that may lead to unsteady gait, clumsiness, walking problems, Enlarged spleen, Enlarged liver, Jaundice at (or shortly after) birth, Learning difficulties and intellectual decline, Seizures, Slurred, irregular speech, Sudden loss of muscle tone that may lead to falls, Tremors, Trouble moving the eyes up and down.

• #17 Niemann-Pick Disease | Baby’s First Test | Newborn Screening | Baby Health

  https://babysfirsttest.org/newborn-screening/conditions/niemann-pick-disease

  Niemann-Pick disease type A (NPD-A), the more severe form of NPD, usually develops in the first few months of life and progress rapidly. Early signs of this form include: Abdominal swelling (due to enlarged liver and spleen), Poor growth, Poor weight gain, Feeding difficulties, Loss of motor skills, Diarrhea, Vomiting, Frequent lung infections, Developmental delay. […] In Niemann-Pick disease type B (NPD-B), symptoms are usually milder and do not develop until later in childhood or adolescence. Early signs of this form include: Abdominal swelling (due to enlarged liver and spleen), Frequent lung infections, Short stature, Low weight, Developmental delay. […] Unfortunately, babies with Niemann-Pick disease type A (NPD-A) have many life-threatening medical problems and usually do not survive past age three.

• #18 Sphingomyelinase Deficiency Clinical Presentation: History, Physical Examination

  https://emedicine.medscape.com/article/951564-clinical

  The clinical presentation and course of NPD type A is relatively uniform and is characterized by normal appearance at birth. Some patients may have neonatal edema, and hydrops fetalis may occur. The first sign detected is usually the presence of hepatosplenomegaly, which is evident at age 3 months and becomes progressively greater. The liver is usually enlarged out of proportion to the spleen. […] The patient’s development seems to progress normally until about age 6 months, followed by a plateau phase from 6 months until about age 15 months. Lastly, rapidly progressive psychomotor and intellectual deterioration occur. Psychomotor development does not progress beyond the 12-month level, and in later stages, the affected child is completely unable to interact with his/her environment. […] Mild hypotonia may be evident by age 6 months, followed by progressive loss of tone and deep tendon reflexes. With disease progression, loss of motor function occurs, and in the final stages, spasticity and rigidity are evident.

• #19 Niemann-Pick disease: Causes, symptoms, treatment, and more

  https://www.medicalnewstoday.com/articles/niemann-pick-disease

  The majority of children with NPA do not survive beyond their first few years due to the severity of the symptoms. […] NPC is also incurable, but the outlook for people with this disease ultimately depends on when complications begin. […] Although all those with the disease have it from birth, the symptoms may sometimes not become apparent until later in life. If the symptoms appear in infancy or childhood, life expectancy is often less than a few years. However, if they develop after the first few years of life, life expectancy extends to adulthood.

• #20 Sphingomyelinase Deficiency Clinical Presentation: History, Physical Examination

  https://emedicine.medscape.com/article/951564-clinical

  Affected infants exhibit feeding problems, failure to thrive, recurrent respiratory tract infections, and irritability. Most children with NPD type A die before age 2-3 years, often from respiratory failure following pulmonary infection. […] The clinical presentation and course in patients with NPD type B disease is milder and more variable. The condition is diagnosed in most patients in infancy or childhood when enlargement of the liver, spleen, or both is detected during routine physical examination. […] At diagnosis, patients with NPD type B also have evidence of mild pulmonary involvement, usually detected as a diffuse reticular or finely nodular infiltration on chest radiograph films. […] In most patients with NPD type B, decreased pulmonary diffusion caused by storage of sphingomyelin in pulmonary macrophages becomes evident in childhood and progresses with age. Severely affected individuals may experience significant pulmonary compromise by age 15-20 years. Such patients have low partial pressure of oxygen (PO2) values and dyspnea on exertion.

• #21 Niemann-Pick Disease (NP) Information

  https://my.clevelandclinic.org/health/articles/6059-niemann-pick-disease-np

  Niemann-Pick disease (NP) refers to a group of inherited metabolic disorders known as lipid storage diseases. Neurological symptoms may include ataxia (lack of muscle control during voluntary movements such as walking), loss of muscle tone, brain degeneration, increased sensitivity to touch, spasticity (stiff muscles and awkward movement), and slurred speech. Other symptoms may include feeding and swallowing difficulties, eye paralysis, learning problems, and an enlarged liver and spleen. […] The disease has three categories. Type A, the most severe form, occurs in early infancy and is seen primarily in Jewish families. It is characterized by progressive weakness, an enlarged liver and spleen, swollen lymph nodes, and profound brain damage by six months of age. Children with this type rarely live beyond 18 months. Type B usually occurs in the pre-teen years, with symptoms that include ataxia and peripheral neuropathy. The brain is generally not affected. Other symptoms include enlarged liver and spleen, and pulmonary difficulties.

• #22 Niemann-Pick disease Information | Mount Sinai – New York

  https://www.mountsinai.org/health-library/diseases-conditions/niemann-pick-disease

  Niemann-Pick disease (NPD) is a group of diseases passed down through families (inherited) in which fatty substances called lipids collect in the cells of the spleen, liver, and brain. […] Each one can cause different symptoms and may occur at different times throughout life. […] Symptoms vary. Other health conditions may cause similar symptoms. The early stages of the disease may only cause a few symptoms. A person may never have all the symptoms. […] Type A usually begins in the first few months of life. Symptoms may include: Abdominal (belly area) swelling by 3 to 6 months of age, Cherry red spot at the back of the eye (on the retina), Feeding difficulties, Loss of early motor skills (gets worse over time). […] Type B symptoms are usually milder. They occur in late childhood or the teenage years. Abdominal swelling may occur in young children. There is almost no brain and nervous system involvement, such as loss of motor skills. Some children may have repeated respiratory infections.

• #23 ASMD Niemann-Pick Disease Type B – NPUK

  https://www.npuk.org/niemann-pick-diseases/asmd-np-b/

  The first symptoms of Niemann-Pick disease Type B (NPB) are usually an enlarged liver and/or spleen in early childhood. […] Symptoms can include: A progressive enlargement of organs, Poor growth, Susceptibility to respiratory infections, Bleeding problems, Bone pain, Increased stress on the heart. […] There is usually no neurological involvement in NPB. Most patients will survive into adulthood, but not without experiencing health problems.

• #24 The Genetic Basis, Lung Involvement, and Therapeutic Options in Niemann–Pick Disease: A Comprehensive Review

  https://www.mdpi.com/2218-273X/14/2/211

  Hepatomegaly is caused by the accumulation of the lipid-laden macrophages in the reticuloendothelial system of the liver. It can cause liver dysfunction, leading to cirrhosis and hepatic failure in some cases. Hepatic involvement, together with lung involvement, represents the most common cause of death in NPD type B. […] Respiratory complications may occur in all three types of Niemann–Pick Disease, with type B being the most common. Pulmonary complications are uncommon in NPD type A, and they usually consist of recurrent respiratory infections, interstitial lung disease, and aspiration pneumonia. […] Patients with NPD type A typically succumb to respiratory failure by the age of 3. In contrast, patients with NPD type B exhibit a more diverse clinical phenotype and life expectancy. […] Specific lung manifestations have been described in NPD type B, including interstitial lung disease (ILD), pulmonary hypertension, alveolar hypoventilation, upper airway obstruction (with or without obstructive sleep apnea syndrome), and recurrent airway infections caused by mucous membrane swelling.

• #25 Niemann-Pick disease: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/niemann-pick-disease/

  Niemann-Pick disease type B usually presents in mid-childhood. The signs and symptoms of this type are similar to type A, but not as severe. People with Niemann-Pick disease type B often have hepatosplenomegaly, recurrent lung infections, and a low number of platelets in the blood (thrombocytopenia). They also have short stature and slowed mineralization of bone (delayed bone age). About one-third of affected individuals have the cherry-red spot eye abnormality or neurological impairment. People with Niemann-Pick disease type B usually survive into adulthood. […] The signs and symptoms of Niemann-Pick disease types C1 and C2 are very similar; these types differ only in their genetic cause. Niemann-Pick disease types C1 and C2 usually become apparent in childhood, although signs and symptoms can develop at any time. People with these types usually develop difficulty coordinating movements (ataxia), an inability to move the eyes vertically (vertical supranuclear gaze palsy), poor muscle tone (dystonia), severe liver disease, and interstitial lung disease. Individuals with Niemann-Pick disease types C1 and C2 have problems with speech and swallowing that worsen over time, eventually interfering with feeding. Affected individuals often experience progressive decline in intellectual function and about one-third have seizures. People with these types may survive into adulthood.

• #26 Sphingomyelinase Deficiency Clinical Presentation: History, Physical Examination

  https://emedicine.medscape.com/article/951564-clinical

  Affected infants exhibit feeding problems, failure to thrive, recurrent respiratory tract infections, and irritability. Most children with NPD type A die before age 2-3 years, often from respiratory failure following pulmonary infection. […] The clinical presentation and course in patients with NPD type B disease is milder and more variable. The condition is diagnosed in most patients in infancy or childhood when enlargement of the liver, spleen, or both is detected during routine physical examination. […] At diagnosis, patients with NPD type B also have evidence of mild pulmonary involvement, usually detected as a diffuse reticular or finely nodular infiltration on chest radiograph films. […] In most patients with NPD type B, decreased pulmonary diffusion caused by storage of sphingomyelin in pulmonary macrophages becomes evident in childhood and progresses with age. Severely affected individuals may experience significant pulmonary compromise by age 15-20 years. Such patients have low partial pressure of oxygen (PO2) values and dyspnea on exertion.

• #27 Niemann-Pick disease: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/niemann-pick-disease/

  Niemann-Pick disease type B usually presents in mid-childhood. The signs and symptoms of this type are similar to type A, but not as severe. People with Niemann-Pick disease type B often have hepatosplenomegaly, recurrent lung infections, and a low number of platelets in the blood (thrombocytopenia). They also have short stature and slowed mineralization of bone (delayed bone age). About one-third of affected individuals have the cherry-red spot eye abnormality or neurological impairment. People with Niemann-Pick disease type B usually survive into adulthood. […] The signs and symptoms of Niemann-Pick disease types C1 and C2 are very similar; these types differ only in their genetic cause. Niemann-Pick disease types C1 and C2 usually become apparent in childhood, although signs and symptoms can develop at any time. People with these types usually develop difficulty coordinating movements (ataxia), an inability to move the eyes vertically (vertical supranuclear gaze palsy), poor muscle tone (dystonia), severe liver disease, and interstitial lung disease. Individuals with Niemann-Pick disease types C1 and C2 have problems with speech and swallowing that worsen over time, eventually interfering with feeding. Affected individuals often experience progressive decline in intellectual function and about one-third have seizures. People with these types may survive into adulthood.

• #28 ASMD Niemann-Pick Disease Type B – NPUK

  https://www.npuk.org/niemann-pick-diseases/asmd-np-b/

  The first symptoms of Niemann-Pick disease Type B (NPB) are usually an enlarged liver and/or spleen in early childhood. […] Symptoms can include: A progressive enlargement of organs, Poor growth, Susceptibility to respiratory infections, Bleeding problems, Bone pain, Increased stress on the heart. […] There is usually no neurological involvement in NPB. Most patients will survive into adulthood, but not without experiencing health problems.

• #29 ASMD Niemann-Pick Disease Type B – NPUK

  https://www.npuk.org/niemann-pick-diseases/asmd-np-b/

  The first symptoms of Niemann-Pick disease Type B (NPB) are usually an enlarged liver and/or spleen in early childhood. […] Symptoms can include: A progressive enlargement of organs, Poor growth, Susceptibility to respiratory infections, Bleeding problems, Bone pain, Increased stress on the heart. […] There is usually no neurological involvement in NPB. Most patients will survive into adulthood, but not without experiencing health problems.

• #30 ASMD Niemann-Pick Disease Type B – NPUK

  https://www.npuk.org/niemann-pick-diseases/asmd-np-b/

  The first symptoms of Niemann-Pick disease Type B (NPB) are usually an enlarged liver and/or spleen in early childhood. […] Symptoms can include: A progressive enlargement of organs, Poor growth, Susceptibility to respiratory infections, Bleeding problems, Bone pain, Increased stress on the heart. […] There is usually no neurological involvement in NPB. Most patients will survive into adulthood, but not without experiencing health problems.

• #31 Niemann-Pick disease: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/niemann-pick-disease/

  Niemann-Pick disease type B usually presents in mid-childhood. The signs and symptoms of this type are similar to type A, but not as severe. People with Niemann-Pick disease type B often have hepatosplenomegaly, recurrent lung infections, and a low number of platelets in the blood (thrombocytopenia). They also have short stature and slowed mineralization of bone (delayed bone age). About one-third of affected individuals have the cherry-red spot eye abnormality or neurological impairment. People with Niemann-Pick disease type B usually survive into adulthood. […] The signs and symptoms of Niemann-Pick disease types C1 and C2 are very similar; these types differ only in their genetic cause. Niemann-Pick disease types C1 and C2 usually become apparent in childhood, although signs and symptoms can develop at any time. People with these types usually develop difficulty coordinating movements (ataxia), an inability to move the eyes vertically (vertical supranuclear gaze palsy), poor muscle tone (dystonia), severe liver disease, and interstitial lung disease. Individuals with Niemann-Pick disease types C1 and C2 have problems with speech and swallowing that worsen over time, eventually interfering with feeding. Affected individuals often experience progressive decline in intellectual function and about one-third have seizures. People with these types may survive into adulthood.

• #32 Niemann-Pick disease Information | Mount Sinai – New York

  https://www.mountsinai.org/health-library/diseases-conditions/niemann-pick-disease

  Niemann-Pick disease (NPD) is a group of diseases passed down through families (inherited) in which fatty substances called lipids collect in the cells of the spleen, liver, and brain. […] Each one can cause different symptoms and may occur at different times throughout life. […] Symptoms vary. Other health conditions may cause similar symptoms. The early stages of the disease may only cause a few symptoms. A person may never have all the symptoms. […] Type A usually begins in the first few months of life. Symptoms may include: Abdominal (belly area) swelling by 3 to 6 months of age, Cherry red spot at the back of the eye (on the retina), Feeding difficulties, Loss of early motor skills (gets worse over time). […] Type B symptoms are usually milder. They occur in late childhood or the teenage years. Abdominal swelling may occur in young children. There is almost no brain and nervous system involvement, such as loss of motor skills. Some children may have repeated respiratory infections.

• #33 ASMD Niemann-Pick Disease Type B – NPUK

  https://www.npuk.org/niemann-pick-diseases/asmd-np-b/

  The first symptoms of Niemann-Pick disease Type B (NPB) are usually an enlarged liver and/or spleen in early childhood. […] Symptoms can include: A progressive enlargement of organs, Poor growth, Susceptibility to respiratory infections, Bleeding problems, Bone pain, Increased stress on the heart. […] There is usually no neurological involvement in NPB. Most patients will survive into adulthood, but not without experiencing health problems.

• #34 Niemann-Pick disease: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/niemann-pick-disease/

  Niemann-Pick disease type B usually presents in mid-childhood. The signs and symptoms of this type are similar to type A, but not as severe. People with Niemann-Pick disease type B often have hepatosplenomegaly, recurrent lung infections, and a low number of platelets in the blood (thrombocytopenia). They also have short stature and slowed mineralization of bone (delayed bone age). About one-third of affected individuals have the cherry-red spot eye abnormality or neurological impairment. People with Niemann-Pick disease type B usually survive into adulthood. […] The signs and symptoms of Niemann-Pick disease types C1 and C2 are very similar; these types differ only in their genetic cause. Niemann-Pick disease types C1 and C2 usually become apparent in childhood, although signs and symptoms can develop at any time. People with these types usually develop difficulty coordinating movements (ataxia), an inability to move the eyes vertically (vertical supranuclear gaze palsy), poor muscle tone (dystonia), severe liver disease, and interstitial lung disease. Individuals with Niemann-Pick disease types C1 and C2 have problems with speech and swallowing that worsen over time, eventually interfering with feeding. Affected individuals often experience progressive decline in intellectual function and about one-third have seizures. People with these types may survive into adulthood.

• #35 Niemann-Pick Disease | Causes, signs, symptoms & treatment

  https://cpdonline.co.uk/knowledge-base/care/niemann-pick-disease/

  For those with type B, survival is possible until adolescence or even early adulthood. There are often problems with complications, however, that make life very difficult in the latter stages of the disease. This includes problems due to having an enlarged spleen or liver and respiratory failure. […] Individuals with type C NPD can have a longer lifespan but the disease is still fatal. The life expectancy of someone with type C will be determined by the age at onset of symptoms. If the symptoms appear early and in infancy, the child will be unlikely to reach age five. However, if symptoms arent present until after the age of five, the individual could live until around age 20.

• #36 Niemann-Pick disease: MedlinePlus Medical EncyclopediaLock

  https://medlineplus.gov/ency/article/001207.htm

  NPD type A is a severe disease. It usually leads to death by age 2 or 3. Those with type B may live into late childhood or adulthood. A child who shows signs of type C before age 1 may not live to school age. Those who show symptoms after entering school may live into their mid-to-late teens. Some may live into their 20s.

• #37 Sphingomyelinase Deficiency Clinical Presentation: History, Physical Examination

  https://emedicine.medscape.com/article/951564-clinical

  Affected infants exhibit feeding problems, failure to thrive, recurrent respiratory tract infections, and irritability. Most children with NPD type A die before age 2-3 years, often from respiratory failure following pulmonary infection. […] The clinical presentation and course in patients with NPD type B disease is milder and more variable. The condition is diagnosed in most patients in infancy or childhood when enlargement of the liver, spleen, or both is detected during routine physical examination. […] At diagnosis, patients with NPD type B also have evidence of mild pulmonary involvement, usually detected as a diffuse reticular or finely nodular infiltration on chest radiograph films. […] In most patients with NPD type B, decreased pulmonary diffusion caused by storage of sphingomyelin in pulmonary macrophages becomes evident in childhood and progresses with age. Severely affected individuals may experience significant pulmonary compromise by age 15-20 years. Such patients have low partial pressure of oxygen (PO2) values and dyspnea on exertion.

• #38 Niemann-Pick disease | Beacon Health System

  https://www.beaconhealthsystem.org/library/diseases-and-conditions/niemann-pick-disease?content_id=CON-20257402

  Type A the most severe form begins in infancy. Symptoms include a liver that becomes too large, severe brain damage and nerve loss that worsens over time. There is no cure. Most children do not live past a few years of age. […] Type B sometimes called juvenile-onset Niemann-Pick disease usually begins later in childhood. It does not involve damage to the brain. Symptoms include nerve pain, problems walking, vision problems, and a liver and spleen that become too large. Lung problems also can happen. Most people with type B live into adulthood. But liver and lung problems worsen over time. Some people have symptoms that overlap between types A and B. […] Niemann-Pick disease type C is caused by changes in the NPC1 and NPC2 genes. With these changes, the body doesn’t have the proteins it needs to move and use cholesterol and other lipids in cells. Cholesterol and other lipids build up in the cells of the liver, spleen or lungs. Over time, the nerves and brain also are affected. This causes problems with eye movements, walking, swallowing, hearing and thinking. Symptoms vary widely, can appear at any age and get worse over time.

• #39 Niemann-Pick Disease Type C: Symptoms, Causes, Treatment

  https://www.healthline.com/health/niemann-pick-disease-type-c

  Signs and symptoms of Niemann-Pick type C disease depend on your age of onset. Symptoms related to problems with your internal organs tend to occur most often in people who develop them at a younger age. Neurological and psychiatric symptoms develop slowly over time. […] Typical signs and symptoms that occur in those younger than 2 years old include: abdominal swelling (ascites), newborn liver disease, which can cause prolonged jaundice, improper vitamin absorption, spleen or liver enlargement. […] Children between 2 and 6 years old may have: low muscle tone (hypotonia), developmental delays, trouble moving their eyes in certain ways, clumsiness, difficulties with coordination (ataxia). […] People between 6 and 15 years old may develop: clumsiness, ataxia, academic difficulties, cognitive impairment, trouble moving eyes in certain ways, seizures, involuntary muscle contractions (dystonia), spasticity.

• #40 Niemann-Pick disease: MedlinePlus Medical EncyclopediaLock

  https://medlineplus.gov/ency/article/001207.htm

  Symptoms vary. Other health conditions may cause similar symptoms. The early stages of the disease may only cause a few symptoms. A person may never have all the symptoms. […] Type A usually begins in the first few months of life. Symptoms may include: Abdominal (belly area) swelling by 3 to 6 months of age, Cherry red spot at the back of the eye (on the retina), Feeding difficulties, Loss of early motor skills (gets worse over time). […] Type B symptoms are usually milder. They occur in late childhood or the teenage years. Abdominal swelling may occur in young children. There is almost no brain and nervous system involvement, such as loss of motor skills. Some children may have repeated respiratory infections. […] Types C and C1 usually affects school-age children. However, it may occur any time between early infancy to adulthood. Symptoms may include: Difficulty moving limbs that may lead to unsteady gait, clumsiness, walking problems, Enlarged spleen, Enlarged liver, Jaundice at (or shortly after) birth, Learning difficulties and intellectual decline, Seizures, Slurred, irregular speech, Sudden loss of muscle tone that may lead to falls, Tremors, Trouble moving the eyes up and down.

• #41 Niemann-Pick disease type C symptomatology: an expert-based clinical description | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-8-166

  Niemann-Pick disease type C (NP-C) is a rare, progressive, irreversible disease leading to disabling neurological manifestations and premature death. […] NP-C is characterised by visceral, neurological and psychiatric manifestations that are not specific to the disease and that can be found in other conditions. […] Early disease detection should rely on seeking a combination of signs and symptoms, rather than isolated findings. […] Examples of combinations which are strongly suggestive of NP-C include: splenomegaly and vertical supranuclear gaze palsy (VSGP); splenomegaly and clumsiness; splenomegaly and schizophrenia-like psychosis; psychotic symptoms and cognitive decline; and ataxia with dystonia, dysarthria/dysphagia and cognitive decline. […] VSGP is a hallmark of NP-C and becomes highly specific of the disease when it occurs in combination with other manifestations (e.g. splenomegaly, ataxia).

• #42

  https://link.springer.com/article/10.1007/s44162-024-00043-0

  Niemann-Pick disease type C poses a significant challenge within the landscape of rare genetic disorders, marked by its connection to variants in the NPC1 or NPC2 genes. This autosomal recessive lipid storage disorder unfolds with a relentless progression of neurological deterioration and a distinctive hallmark of hepatosplenomegaly. […] NPD-C manifests with its predominant impact on the nervous system, giving rise to distinctive clinical manifestations that include hypotonia, motor retardation, vertical supranuclear gaze palsy (VSGP), and cataplexy. These neurological symptoms characterize the debilitating nature of NPD-C, underlining the profound impact on both motor and cognitive functions. Hypotonia and motor retardation contribute to the progressive decline in motor skills, while VSGP represents a notable ophthalmologic manifestation. Cataplexy, characterized by sudden loss of muscle tone, further adds to the complex clinical picture of NPD-C.

• #43 Niemann-Pick disease type C | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-5-16

  The clinical presentation of NP-C is extremely heterogeneous, with an age of onset ranging from the perinatal period until well into adult age (as late as the seventh decade of life). Similarly, the lifespan of the patients varies between a few days until over 60 years of age, although a majority of cases die between 10 and 25 years of age. […] Importantly, visceral involvement (of liver, spleen, and sometimes lung) and neurologic or psychiatric manifestations arise at different times, and they also follow completely independent courses. Apart from a small subset of patients who die at birth, or in the first 6 months of life from hepatic or respiratory failure, and exceptional adult cases, all patients ultimately will develop a progressive and fatal neurological disease. […] In typical patients, the neurologic disorder consists mainly of cerebellar ataxia, dysarthria, dysphagia, and progressive dementia, and the majority of cases show a characteristic vertical supranuclear gaze palsy (VSGP). Cataplexy, seizures, and dystonia are other quite common features, and psychiatric disturbances are frequent in late-onset patients.

• #44 Niemann-Pick disease type C | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-5-16

  The clinical presentation of NP-C is extremely heterogeneous, with an age of onset ranging from the perinatal period until well into adult age (as late as the seventh decade of life). Similarly, the lifespan of the patients varies between a few days until over 60 years of age, although a majority of cases die between 10 and 25 years of age. […] Importantly, visceral involvement (of liver, spleen, and sometimes lung) and neurologic or psychiatric manifestations arise at different times, and they also follow completely independent courses. Apart from a small subset of patients who die at birth, or in the first 6 months of life from hepatic or respiratory failure, and exceptional adult cases, all patients ultimately will develop a progressive and fatal neurological disease. […] In typical patients, the neurologic disorder consists mainly of cerebellar ataxia, dysarthria, dysphagia, and progressive dementia, and the majority of cases show a characteristic vertical supranuclear gaze palsy (VSGP). Cataplexy, seizures, and dystonia are other quite common features, and psychiatric disturbances are frequent in late-onset patients.

• #45

  https://omim.org/entry/257220

  Niemann-Pick disease type C has a highly variable clinical phenotype. […] Patients with the 'classic’ childhood onset type C usually appear normal for 1 or 2 years with symptoms appearing between 2 and 4 years. […] They gradually develop neurologic abnormalities which are initially manifested by ataxia, grand mal seizures, and loss of previously learned speech. […] Spasticity is striking and seizures, particularly myoclonic jerks, are common. […] Other features include dystonia, vertical supranuclear gaze palsy, dementia, and psychiatric manifestations. […] In general, hepatosplenomegaly is less striking than in types A and B, although it can be lethal in some. […] Cholestatic jaundice occurs in some patients. […] In the childhood-onset form, death usually occurs at age 5 to 15.

• #46 Niemann-Pick Disease Type C | Boston Children’s Hospital

  https://www.childrenshospital.org/conditions/niemann-pick-disease-type-c

  Signs and symptoms of Niemann-Pick disease type C generally first appear in childhood, though they can present at any time, including adolescence or adulthood. […] Because of the progressive nature of Niemann-Pick disease, signs and symptoms become more pronounced over time. […] Symptoms may include: Enlarged liver and spleen (hepatosplenomegaly), Difficulty coordinating movement (ataxia), Abnormal eye movements (vertical supranuclear gaze palsy), Poor muscle tone (hypotonia), Severe liver disease, Frequent respiratory infections, Difficulty with speech, Difficulty with swallowing and feeding, Loss of cognitive skills, Seizures.

• #47 Niemann-Pick Disease Type C (NPC) – Rare Awareness Rare Education

  https://rareportal.org.au/rare-disease/niemann-pick-disease-type-c-npc/

  Niemann-Pick disease type C (NPC) is a type of lysosomal storage disorder (under the class of sphingolipidosis). In NPC, cells in the body are unable to properly transport cholesterol and other fatty substances (lipids), resulting in their accumulation. NPC is considered to be a childhood dementia disorder, characterised by progressive brain damage (neurodegeneration). Symptoms can be highly variable between individuals and can develop at any age of life. In some cases, NPC can be life-threatening in the first few months of life, whilst for other individuals, symptoms may not be obvious until adulthood. […] The disease presentation of Niemann-Pick disease type C (NPC) is highly variable between individuals and can change over an individuals lifetime. Babies may present with jaundice, poor muscle tone (hypotonia), enlarged liver and spleen (hepatosplenomegaly), as well as liver and lung disease that can lead to life-threatening complications. Neurological symptoms often emerge in childhood, but in some cases, do not present until adulthood. Symptoms are often progressive and may include: Difficulty in controlling and posturing of limbs (dystonia), Loss of muscle control leading to lack of balance, coordination and trouble walking (ataxia) this may present as unsteadiness of gait and clumsiness, Weakness of speech muscles, resulting in slurred or slow and unclear speech (dysarthria), Difficulty in swallowing (dysphagia); assisted feeding may be required in some cases, Difficulty with upward and downward eye movements (Vertical Supranuclear Gaze Palsy, VSGP), Generalised loss of muscle tone whilst still conscious, triggered by laughing (gelastic cataplexy), Seizures, Learning difficulties (cognitive dysfunction) and progressive intellectual decline (dementia), Psychiatric disturbances, particularly in adults. […] Individuals with NPC may also be at risk of aspiration pneumonia, which can be life-threatening. It is an infection of the lungs caused by inhaling saliva, food, or liquid into the airway, which can be due to the inability to swallow.

• #48 Niemann-Pick disease type C | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-5-16

  The clinical presentation of NP-C is extremely heterogeneous, with an age of onset ranging from the perinatal period until well into adult age (as late as the seventh decade of life). Similarly, the lifespan of the patients varies between a few days until over 60 years of age, although a majority of cases die between 10 and 25 years of age. […] Importantly, visceral involvement (of liver, spleen, and sometimes lung) and neurologic or psychiatric manifestations arise at different times, and they also follow completely independent courses. Apart from a small subset of patients who die at birth, or in the first 6 months of life from hepatic or respiratory failure, and exceptional adult cases, all patients ultimately will develop a progressive and fatal neurological disease. […] In typical patients, the neurologic disorder consists mainly of cerebellar ataxia, dysarthria, dysphagia, and progressive dementia, and the majority of cases show a characteristic vertical supranuclear gaze palsy (VSGP). Cataplexy, seizures, and dystonia are other quite common features, and psychiatric disturbances are frequent in late-onset patients.

• #49 Understanding the phenotypic variability in Niemann-Pick disease type C (NPC): a need for precision medicine | npj Genomic Medicine

  https://www.nature.com/articles/s41525-023-00365-w

  This is the second most frequent form of the disease. The first sign is splenomegaly and, less commonly, hepatosplenomegaly, which also may be detected earlier (including the neonatal period). These patients suffer a significant motor impairment and a variable cognitive decline. […] Adolescent and adult-onset NPC patients may represent up to a third of all NPC patients. This group may encompass a broad array of time to symptom onset/rate of disease progression. Neurological manifestations frequently occur in these patients. The typical presentation is a history of severe progressive ataxia, dystonia, VSGP, variable cognitive decline, and psychotic symptoms. […] The psychiatric symptoms include paranoid delusions, auditory or visual hallucinations, and interpretative thoughts. Other mental manifestations include depression, behavioral problems with aggressiveness, and social isolation. Several cases have also been reported with bipolar disorder and obsessive-compulsive.

• #50 Niemann-Pick disease: MedlinePlus Medical EncyclopediaLock

  https://medlineplus.gov/ency/article/001207.htm

  Symptoms vary. Other health conditions may cause similar symptoms. The early stages of the disease may only cause a few symptoms. A person may never have all the symptoms. […] Type A usually begins in the first few months of life. Symptoms may include: Abdominal (belly area) swelling by 3 to 6 months of age, Cherry red spot at the back of the eye (on the retina), Feeding difficulties, Loss of early motor skills (gets worse over time). […] Type B symptoms are usually milder. They occur in late childhood or the teenage years. Abdominal swelling may occur in young children. There is almost no brain and nervous system involvement, such as loss of motor skills. Some children may have repeated respiratory infections. […] Types C and C1 usually affects school-age children. However, it may occur any time between early infancy to adulthood. Symptoms may include: Difficulty moving limbs that may lead to unsteady gait, clumsiness, walking problems, Enlarged spleen, Enlarged liver, Jaundice at (or shortly after) birth, Learning difficulties and intellectual decline, Seizures, Slurred, irregular speech, Sudden loss of muscle tone that may lead to falls, Tremors, Trouble moving the eyes up and down.

• #51 Niemann-Pick Disease Type C (NPC) – Rare Awareness Rare Education

  https://rareportal.org.au/rare-disease/niemann-pick-disease-type-c-npc/

  Niemann-Pick disease type C (NPC) is a type of lysosomal storage disorder (under the class of sphingolipidosis). In NPC, cells in the body are unable to properly transport cholesterol and other fatty substances (lipids), resulting in their accumulation. NPC is considered to be a childhood dementia disorder, characterised by progressive brain damage (neurodegeneration). Symptoms can be highly variable between individuals and can develop at any age of life. In some cases, NPC can be life-threatening in the first few months of life, whilst for other individuals, symptoms may not be obvious until adulthood. […] The disease presentation of Niemann-Pick disease type C (NPC) is highly variable between individuals and can change over an individuals lifetime. Babies may present with jaundice, poor muscle tone (hypotonia), enlarged liver and spleen (hepatosplenomegaly), as well as liver and lung disease that can lead to life-threatening complications. Neurological symptoms often emerge in childhood, but in some cases, do not present until adulthood. Symptoms are often progressive and may include: Difficulty in controlling and posturing of limbs (dystonia), Loss of muscle control leading to lack of balance, coordination and trouble walking (ataxia) this may present as unsteadiness of gait and clumsiness, Weakness of speech muscles, resulting in slurred or slow and unclear speech (dysarthria), Difficulty in swallowing (dysphagia); assisted feeding may be required in some cases, Difficulty with upward and downward eye movements (Vertical Supranuclear Gaze Palsy, VSGP), Generalised loss of muscle tone whilst still conscious, triggered by laughing (gelastic cataplexy), Seizures, Learning difficulties (cognitive dysfunction) and progressive intellectual decline (dementia), Psychiatric disturbances, particularly in adults. […] Individuals with NPC may also be at risk of aspiration pneumonia, which can be life-threatening. It is an infection of the lungs caused by inhaling saliva, food, or liquid into the airway, which can be due to the inability to swallow.

• #52 Niemann-Pick Disease Type C: Symptoms, Causes, Treatment

  https://www.healthline.com/health/niemann-pick-disease-type-c

  Signs and symptoms of Niemann-Pick type C disease depend on your age of onset. Symptoms related to problems with your internal organs tend to occur most often in people who develop them at a younger age. Neurological and psychiatric symptoms develop slowly over time. […] Typical signs and symptoms that occur in those younger than 2 years old include: abdominal swelling (ascites), newborn liver disease, which can cause prolonged jaundice, improper vitamin absorption, spleen or liver enlargement. […] Children between 2 and 6 years old may have: low muscle tone (hypotonia), developmental delays, trouble moving their eyes in certain ways, clumsiness, difficulties with coordination (ataxia). […] People between 6 and 15 years old may develop: clumsiness, ataxia, academic difficulties, cognitive impairment, trouble moving eyes in certain ways, seizures, involuntary muscle contractions (dystonia), spasticity.

• #53 Niemann-Pick disease type C | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-5-16

  The age of onset of the systemic symptoms is not related with that of the neurological disease (the latter can occur many years or even decades later), while there is a correlation between the age of onset of the neurological symptoms and the general further course of the disease and lifespan. […] Patients with the severe neurologic early infantile form often die between 3 and 5 years of age, those with a late-infantile neurologic onset usually between 7 and 12. Patients with a juvenile neurologic onset survive until adolescence or later, with a sizable proportion reaching the age of 30. In a review of 68 cases with adult onset, the mean age at death (on 20 patients) was 38 10.2 years, but some patients have reached the age of 70.

• #54 Understanding the phenotypic variability in Niemann-Pick disease type C (NPC): a need for precision medicine | npj Genomic Medicine

  https://www.nature.com/articles/s41525-023-00365-w

  Niemann-Pick type C (NPC) disease is a lysosomal storage disease (LSD) characterized by the buildup of endo-lysosomal cholesterol and glycosphingolipids due to loss of function mutations in the NPC1 and NPC2 genes. NPC patients can present with a broad phenotypic spectrum, with differences at the age of onset, rate of progression, severity, organs involved, effects on the central nervous system, and even response to pharmacological treatments. […] Clinical presentations of NPC disease are highly heterogeneous and vary from a rapidly progressing neonatal form to an adult-onset chronic neurodegenerative condition. The life expectancy of the patients ranges from a few days until over 60 years of age, but most patients survive to 10-25 years of age, although probably this is an underestimation.

• #55 Niemann-Pick disease type C | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-5-16

  The clinical presentation of NP-C is extremely heterogeneous, with an age of onset ranging from the perinatal period until well into adult age (as late as the seventh decade of life). Similarly, the lifespan of the patients varies between a few days until over 60 years of age, although a majority of cases die between 10 and 25 years of age. […] Importantly, visceral involvement (of liver, spleen, and sometimes lung) and neurologic or psychiatric manifestations arise at different times, and they also follow completely independent courses. Apart from a small subset of patients who die at birth, or in the first 6 months of life from hepatic or respiratory failure, and exceptional adult cases, all patients ultimately will develop a progressive and fatal neurological disease. […] In typical patients, the neurologic disorder consists mainly of cerebellar ataxia, dysarthria, dysphagia, and progressive dementia, and the majority of cases show a characteristic vertical supranuclear gaze palsy (VSGP). Cataplexy, seizures, and dystonia are other quite common features, and psychiatric disturbances are frequent in late-onset patients.

• #56 Niemann-Pick disease type C | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-5-16

  The clinical presentation of NP-C is extremely heterogeneous, with an age of onset ranging from the perinatal period until well into adult age (as late as the seventh decade of life). Similarly, the lifespan of the patients varies between a few days until over 60 years of age, although a majority of cases die between 10 and 25 years of age. […] Importantly, visceral involvement (of liver, spleen, and sometimes lung) and neurologic or psychiatric manifestations arise at different times, and they also follow completely independent courses. Apart from a small subset of patients who die at birth, or in the first 6 months of life from hepatic or respiratory failure, and exceptional adult cases, all patients ultimately will develop a progressive and fatal neurological disease. […] In typical patients, the neurologic disorder consists mainly of cerebellar ataxia, dysarthria, dysphagia, and progressive dementia, and the majority of cases show a characteristic vertical supranuclear gaze palsy (VSGP). Cataplexy, seizures, and dystonia are other quite common features, and psychiatric disturbances are frequent in late-onset patients.

• #57 Niemann-Pick Disease Type C: Symptoms, Causes, Treatment

  https://www.healthline.com/health/niemann-pick-disease-type-c

  Along with neurological symptoms that can onset during childhood, adults may also have: early onset dementia, psychiatric disorders like treatment-resistant depression, schizophrenia, bipolar disorder. […] The outlook for people with NPD type C varies depending on when your symptoms occur. The chances of survival are very poor if symptoms develop in infancy. If it develops after the age of 5 years old, people may live to be older than 20 years old. […] Some children develop severe, life threatening complications early, and others have mild symptoms that remain undiagnosed into adulthood. Life expectancy can range anywhere from a few days to over 60 years but is most commonly between 10-25 years of age. […] Currently, NPD type C has no cure, and treatment is largely supportive. People with the disease generally have a better outlook when symptoms develop when they’re at an older age.

• #58 Niemann-Pick disease type C | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-5-16

  The age of onset of the systemic symptoms is not related with that of the neurological disease (the latter can occur many years or even decades later), while there is a correlation between the age of onset of the neurological symptoms and the general further course of the disease and lifespan. […] Patients with the severe neurologic early infantile form often die between 3 and 5 years of age, those with a late-infantile neurologic onset usually between 7 and 12. Patients with a juvenile neurologic onset survive until adolescence or later, with a sizable proportion reaching the age of 30. In a review of 68 cases with adult onset, the mean age at death (on 20 patients) was 38 10.2 years, but some patients have reached the age of 70.

• #59 Sphingomyelinase Deficiency Clinical Presentation: History, Physical Examination

  https://emedicine.medscape.com/article/951564-clinical

  The clinical presentation and course of NPD type A is relatively uniform and is characterized by normal appearance at birth. Some patients may have neonatal edema, and hydrops fetalis may occur. The first sign detected is usually the presence of hepatosplenomegaly, which is evident at age 3 months and becomes progressively greater. The liver is usually enlarged out of proportion to the spleen. […] The patient’s development seems to progress normally until about age 6 months, followed by a plateau phase from 6 months until about age 15 months. Lastly, rapidly progressive psychomotor and intellectual deterioration occur. Psychomotor development does not progress beyond the 12-month level, and in later stages, the affected child is completely unable to interact with his/her environment. […] Mild hypotonia may be evident by age 6 months, followed by progressive loss of tone and deep tendon reflexes. With disease progression, loss of motor function occurs, and in the final stages, spasticity and rigidity are evident.

• #60 What Is Niemann-Pick Disease?

  https://www.verywellhealth.com/niemann-pick-disease-4158754

  Niemann-Pick disease causes a variety of medical problems, and it often advances rapidly. The symptoms and effects of all of the variants of Niemann-Pick disease result from the buildup of sphingomyelin, a type of fat, in the body. […] Unfortunately, children with this disease are not expected to survive beyond age 3 or 4. […] The symptoms begin around age six months and include: slow physical growth, weak muscles and weak muscle tone, trouble eating, breathing problems and slow or delayed development of cognitive abilities such as sitting up and speaking. Often, infants with Niemann-Pick type A develop normally or almost normally for the first few months of life and then begin to have symptoms. […] The symptoms begin during adulthood and can include a large liver, a large spleen, breathing difficulties, and bleeding. Older adults typically have a better outcome and longer survival than younger adults who have this disease variant.

• #61 Niemann-Pick disease: MedlinePlus Medical EncyclopediaLock

  https://medlineplus.gov/ency/article/001207.htm

  Symptoms vary. Other health conditions may cause similar symptoms. The early stages of the disease may only cause a few symptoms. A person may never have all the symptoms. […] Type A usually begins in the first few months of life. Symptoms may include: Abdominal (belly area) swelling by 3 to 6 months of age, Cherry red spot at the back of the eye (on the retina), Feeding difficulties, Loss of early motor skills (gets worse over time). […] Type B symptoms are usually milder. They occur in late childhood or the teenage years. Abdominal swelling may occur in young children. There is almost no brain and nervous system involvement, such as loss of motor skills. Some children may have repeated respiratory infections. […] Types C and C1 usually affects school-age children. However, it may occur any time between early infancy to adulthood. Symptoms may include: Difficulty moving limbs that may lead to unsteady gait, clumsiness, walking problems, Enlarged spleen, Enlarged liver, Jaundice at (or shortly after) birth, Learning difficulties and intellectual decline, Seizures, Slurred, irregular speech, Sudden loss of muscle tone that may lead to falls, Tremors, Trouble moving the eyes up and down.

• #62 Sphingomyelinase Deficiency Clinical Presentation: History, Physical Examination

  https://emedicine.medscape.com/article/951564-clinical

  Affected infants exhibit feeding problems, failure to thrive, recurrent respiratory tract infections, and irritability. Most children with NPD type A die before age 2-3 years, often from respiratory failure following pulmonary infection. […] The clinical presentation and course in patients with NPD type B disease is milder and more variable. The condition is diagnosed in most patients in infancy or childhood when enlargement of the liver, spleen, or both is detected during routine physical examination. […] At diagnosis, patients with NPD type B also have evidence of mild pulmonary involvement, usually detected as a diffuse reticular or finely nodular infiltration on chest radiograph films. […] In most patients with NPD type B, decreased pulmonary diffusion caused by storage of sphingomyelin in pulmonary macrophages becomes evident in childhood and progresses with age. Severely affected individuals may experience significant pulmonary compromise by age 15-20 years. Such patients have low partial pressure of oxygen (PO2) values and dyspnea on exertion.

• #63 Niemann-Pick Disease | Causes, signs, symptoms & treatment

  https://cpdonline.co.uk/knowledge-base/care/niemann-pick-disease/

  By the childs first birthday, youll often see a psychomotor retardation. This is characterised by slow movements for things that usually require little thought like hand gestures, walking and picking things up. The child may also display regressions in the developmental milestones that theyve already achieved. Type A patients also have what is known as a cherry-red spot in their eyes. This is a small, circular red dot in the macula area of the eye. […] With type B, youre most likely to see symptoms midway through childhood and these arent as severe. Type B patients will have recurrent lung infections, enlarged liver and spleen, slower bone growth, low platelet level and sometimes (1 in 3) a cherry-red spot in the eye. There will also be neurological symptoms. […] The symptoms of type C NPD can occur at any time, but they usually present themselves during childhood. The affected person might experience dystonia (twisting and spasming muscles), dysphonia (a hoarse voice), dysphagia (difficulty swallowing), liver disease, lung disease, ataxia (problems with coordination, balance and speech), and supranuclear gaze palsy (SNGP).

• #64 Niemann-Pick disease: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/niemann-pick-disease/

  Niemann-Pick disease is a condition that affects many body systems. It has a wide range of symptoms that vary in severity. […] Infants with Niemann-Pick disease type A usually develop an enlarged liver and spleen (hepatosplenomegaly) by age 3 months and fail to gain weight and grow at the expected rate (failure to thrive). The affected children develop normally until around age 1 year when they experience a progressive loss of mental abilities and movement (psychomotor regression). Children with Niemann-Pick disease type A also develop widespread lung damage (interstitial lung disease) that can cause recurrent lung infections and eventually lead to respiratory failure. All affected children have an eye abnormality called a cherry-red spot, which can be identified with an eye examination. Children with Niemann-Pick disease type A generally do not survive past early childhood.

• #65 Sphingomyelinase Deficiency Clinical Presentation: History, Physical Examination

  https://emedicine.medscape.com/article/951564-clinical

  The clinical presentation and course of NPD type A is relatively uniform and is characterized by normal appearance at birth. Some patients may have neonatal edema, and hydrops fetalis may occur. The first sign detected is usually the presence of hepatosplenomegaly, which is evident at age 3 months and becomes progressively greater. The liver is usually enlarged out of proportion to the spleen. […] The patient’s development seems to progress normally until about age 6 months, followed by a plateau phase from 6 months until about age 15 months. Lastly, rapidly progressive psychomotor and intellectual deterioration occur. Psychomotor development does not progress beyond the 12-month level, and in later stages, the affected child is completely unable to interact with his/her environment. […] Mild hypotonia may be evident by age 6 months, followed by progressive loss of tone and deep tendon reflexes. With disease progression, loss of motor function occurs, and in the final stages, spasticity and rigidity are evident.

• #66 Niemann-Pick Disease, Types A and B | Hereditary Ocular Diseases

  https://disorders.eyes.arizona.edu/disorders/niemann-pick-disease-types-and-b

  Affected infants usually develop prominent cherry red spots during the first 12 months of life and the entire retina has an opaque appearance. […] Vision in the first year of life is likely normal as infants have normal fixation, pupillary reactions, and following movements with no nystagmus. However, by about 2 years of age visual responsiveness may be lost. […] Both the age of onset of neurological symptoms and the rate of progression are highly variable. Type A, known as the infantile form, is the more severe disease with onset by 6 months of age with rapid progression and few patients survive beyond three years of age. […] Neonates seem to develop normally for the first 6 months but then become irritable, fail to thrive and feed poorly. Hepatosplenomegaly is usually the first physical sign. Hypotonia and pulmonary infections are common. These patients never achieve normal developmental milestones such as sitting, walking or crawling and the neurodegeneration is relentless from this point with the median age at death 21 months, usually from respiratory disease. […] The less severe form of Niemann-Pick disease, type B, has a later onset and slower course. Such patients have widespread visceral disease affecting liver, spleen and lungs with hyperlipidemia but few neurologic symptoms and often survive into adulthood.

• #67 Niemann-Pick Disease, Types A and B | Hereditary Ocular Diseases

  https://disorders.eyes.arizona.edu/disorders/niemann-pick-disease-types-and-b

  Affected infants usually develop prominent cherry red spots during the first 12 months of life and the entire retina has an opaque appearance. […] Vision in the first year of life is likely normal as infants have normal fixation, pupillary reactions, and following movements with no nystagmus. However, by about 2 years of age visual responsiveness may be lost. […] Both the age of onset of neurological symptoms and the rate of progression are highly variable. Type A, known as the infantile form, is the more severe disease with onset by 6 months of age with rapid progression and few patients survive beyond three years of age. […] Neonates seem to develop normally for the first 6 months but then become irritable, fail to thrive and feed poorly. Hepatosplenomegaly is usually the first physical sign. Hypotonia and pulmonary infections are common. These patients never achieve normal developmental milestones such as sitting, walking or crawling and the neurodegeneration is relentless from this point with the median age at death 21 months, usually from respiratory disease. […] The less severe form of Niemann-Pick disease, type B, has a later onset and slower course. Such patients have widespread visceral disease affecting liver, spleen and lungs with hyperlipidemia but few neurologic symptoms and often survive into adulthood.

• #68 Niemann-Pick Disease – Pediatrics – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/pediatrics/inherited-disorders-of-metabolism/niemann-pick-disease

  Children with type A have 5% of normal sphingomyelinase activity. The disease is characterized by hepatosplenomegaly, failure to thrive, and rapidly progressive neurodegeneration. Death occurs by age 2 or 3 years. […] Patients with type B have sphingomyelinase activity within 5 to 10% of normal. Type B is more variable clinically than type A. Hepatosplenomegaly and lymphadenopathy may occur. Pancytopenia is common. Most patients with type B have little or no neurologic involvement, may have intellectual disability, and survive into adulthood; they may be clinically indistinguishable from those with type I Gaucher disease. In severe cases of type B, progressive pulmonary infiltrates cause major complications. […] Children with type C develop symptoms usually during childhood, with seizures and neurologic deterioration. Type C is always fatal, and most children die before age 20.

• #69 ASMD Niemann-Pick Disease Type B – NPUK

  https://www.npuk.org/niemann-pick-diseases/asmd-np-b/

  The first symptoms of Niemann-Pick disease Type B (NPB) are usually an enlarged liver and/or spleen in early childhood. […] Symptoms can include: A progressive enlargement of organs, Poor growth, Susceptibility to respiratory infections, Bleeding problems, Bone pain, Increased stress on the heart. […] There is usually no neurological involvement in NPB. Most patients will survive into adulthood, but not without experiencing health problems.

• #70 Niemann-Pick Disease | Baby’s First Test | Newborn Screening | Baby Health

  https://babysfirsttest.org/newborn-screening/conditions/niemann-pick-disease

  Niemann-Pick disease type A (NPD-A), the more severe form of NPD, usually develops in the first few months of life and progress rapidly. Early signs of this form include: Abdominal swelling (due to enlarged liver and spleen), Poor growth, Poor weight gain, Feeding difficulties, Loss of motor skills, Diarrhea, Vomiting, Frequent lung infections, Developmental delay. […] In Niemann-Pick disease type B (NPD-B), symptoms are usually milder and do not develop until later in childhood or adolescence. Early signs of this form include: Abdominal swelling (due to enlarged liver and spleen), Frequent lung infections, Short stature, Low weight, Developmental delay. […] Unfortunately, babies with Niemann-Pick disease type A (NPD-A) have many life-threatening medical problems and usually do not survive past age three.

• #71 Sphingomyelinase Deficiency Clinical Presentation: History, Physical Examination

  https://emedicine.medscape.com/article/951564-clinical

  Affected infants exhibit feeding problems, failure to thrive, recurrent respiratory tract infections, and irritability. Most children with NPD type A die before age 2-3 years, often from respiratory failure following pulmonary infection. […] The clinical presentation and course in patients with NPD type B disease is milder and more variable. The condition is diagnosed in most patients in infancy or childhood when enlargement of the liver, spleen, or both is detected during routine physical examination. […] At diagnosis, patients with NPD type B also have evidence of mild pulmonary involvement, usually detected as a diffuse reticular or finely nodular infiltration on chest radiograph films. […] In most patients with NPD type B, decreased pulmonary diffusion caused by storage of sphingomyelin in pulmonary macrophages becomes evident in childhood and progresses with age. Severely affected individuals may experience significant pulmonary compromise by age 15-20 years. Such patients have low partial pressure of oxygen (PO2) values and dyspnea on exertion.

• #72 Sphingomyelinase Deficiency Clinical Presentation: History, Physical Examination

  https://emedicine.medscape.com/article/951564-clinical

  Affected infants exhibit feeding problems, failure to thrive, recurrent respiratory tract infections, and irritability. Most children with NPD type A die before age 2-3 years, often from respiratory failure following pulmonary infection. […] The clinical presentation and course in patients with NPD type B disease is milder and more variable. The condition is diagnosed in most patients in infancy or childhood when enlargement of the liver, spleen, or both is detected during routine physical examination. […] At diagnosis, patients with NPD type B also have evidence of mild pulmonary involvement, usually detected as a diffuse reticular or finely nodular infiltration on chest radiograph films. […] In most patients with NPD type B, decreased pulmonary diffusion caused by storage of sphingomyelin in pulmonary macrophages becomes evident in childhood and progresses with age. Severely affected individuals may experience significant pulmonary compromise by age 15-20 years. Such patients have low partial pressure of oxygen (PO2) values and dyspnea on exertion.

• #73 Niemann-Pick Disease | Causes, signs, symptoms & treatment

  https://cpdonline.co.uk/knowledge-base/care/niemann-pick-disease/

  For those with type B, survival is possible until adolescence or even early adulthood. There are often problems with complications, however, that make life very difficult in the latter stages of the disease. This includes problems due to having an enlarged spleen or liver and respiratory failure. […] Individuals with type C NPD can have a longer lifespan but the disease is still fatal. The life expectancy of someone with type C will be determined by the age at onset of symptoms. If the symptoms appear early and in infancy, the child will be unlikely to reach age five. However, if symptoms arent present until after the age of five, the individual could live until around age 20.

• #74 ASMD Niemann-Pick Disease Type B – NPUK

  https://www.npuk.org/niemann-pick-diseases/asmd-np-b/

  The first symptoms of Niemann-Pick disease Type B (NPB) are usually an enlarged liver and/or spleen in early childhood. […] Symptoms can include: A progressive enlargement of organs, Poor growth, Susceptibility to respiratory infections, Bleeding problems, Bone pain, Increased stress on the heart. […] There is usually no neurological involvement in NPB. Most patients will survive into adulthood, but not without experiencing health problems.

• #75 Sphingomyelinase Deficiency Clinical Presentation: History, Physical Examination

  https://emedicine.medscape.com/article/951564-clinical

  Patients with NPD type A/B (also known as intermediate phenotype or chronic neurovisceral ASMD) have symptom onset in early childhood and slower progression of mild neurologic symptoms than do patients with NPD type A, following a period of normal development. Neurologic symptom progression may last from 2-7 years. Neurologic symptoms may include peripheral neuropathy, extrapyramidal signs, psychiatric symptoms, learning disabilities, and ataxia. […] The liver and spleen are usually affected, with hepatosplenomegaly occurring. Liver disease may progress to portal hypertension and fibrosis, with liver function tests elevated. […] Lung involvement is similar to that in type A, and patients may develop interstitial lung disease and a restrictive pattern on pulmonary function testing. […] Some patients with NPD type A/B may have associated neurologic findings, including cerebellar signs, nystagmus, extrapyramidal involvement, and intellectual disability. […] Thrombocytopenia and bleeding tendencies, recurrent ear infections, and headaches are also noted in these patients.

• #76 Niemann-Pick Disease | Baby’s First Test | Newborn Screening | Baby Health

  https://babysfirsttest.org/newborn-screening/conditions/niemann-pick-disease

  Niemann-Pick disease type B (NPD-B) is generally associated with milder symptoms and a longer lifespan. In fact, individuals with this form of the condition usually live into adulthood, though they may have many health complications. […] Early detection and proper treatment can help improve the quality of life in babies with NPD-A and the long term outcome of babies with NPD-B. This is why newborn screening for NPD is so important.

• #77 Understanding the phenotypic variability in Niemann-Pick disease type C (NPC): a need for precision medicine | npj Genomic Medicine

  https://www.nature.com/articles/s41525-023-00365-w

  Niemann-Pick type C (NPC) disease is a lysosomal storage disease (LSD) characterized by the buildup of endo-lysosomal cholesterol and glycosphingolipids due to loss of function mutations in the NPC1 and NPC2 genes. NPC patients can present with a broad phenotypic spectrum, with differences at the age of onset, rate of progression, severity, organs involved, effects on the central nervous system, and even response to pharmacological treatments. […] Clinical presentations of NPC disease are highly heterogeneous and vary from a rapidly progressing neonatal form to an adult-onset chronic neurodegenerative condition. The life expectancy of the patients ranges from a few days until over 60 years of age, but most patients survive to 10-25 years of age, although probably this is an underestimation.

• #78 Niemann-Pick Disease Type C: Symptoms, Causes, Treatment

  https://www.healthline.com/health/niemann-pick-disease-type-c

  Signs and symptoms of Niemann-Pick type C disease depend on your age of onset. Symptoms related to problems with your internal organs tend to occur most often in people who develop them at a younger age. Neurological and psychiatric symptoms develop slowly over time. […] Typical signs and symptoms that occur in those younger than 2 years old include: abdominal swelling (ascites), newborn liver disease, which can cause prolonged jaundice, improper vitamin absorption, spleen or liver enlargement. […] Children between 2 and 6 years old may have: low muscle tone (hypotonia), developmental delays, trouble moving their eyes in certain ways, clumsiness, difficulties with coordination (ataxia). […] People between 6 and 15 years old may develop: clumsiness, ataxia, academic difficulties, cognitive impairment, trouble moving eyes in certain ways, seizures, involuntary muscle contractions (dystonia), spasticity.

• #79

  https://link.springer.com/article/10.1007/s44162-024-00043-0

  The onset of neurological symptoms in individuals with NPD-C typically commences around eight to nine months of age, becoming more pronounced and discernible by the age of 1 to 2 years. Children diagnosed with NPD-C in the late infantile period typically face a challenging prognosis, with overall survival rarely extending beyond 6 years. This group of patients is characterized by the initial manifestation of hepatosplenomegaly, alongside the subtle yet significant presentation of early downward gaze palsy, a symptom that may not be easily detected during the early stages. As the disease progresses, late infantile children may also experience ataxia, unsteady walking, and a propensity to falls. Additionally, cognitive deficits may insidiously emerge during this period, further complicating the clinical picture.

• #80

  https://link.springer.com/article/10.1007/s44162-024-00043-0

  The onset of neurological symptoms in individuals with NPD-C typically commences around eight to nine months of age, becoming more pronounced and discernible by the age of 1 to 2 years. Children diagnosed with NPD-C in the late infantile period typically face a challenging prognosis, with overall survival rarely extending beyond 6 years. This group of patients is characterized by the initial manifestation of hepatosplenomegaly, alongside the subtle yet significant presentation of early downward gaze palsy, a symptom that may not be easily detected during the early stages. As the disease progresses, late infantile children may also experience ataxia, unsteady walking, and a propensity to falls. Additionally, cognitive deficits may insidiously emerge during this period, further complicating the clinical picture.

• #81

  https://link.springer.com/article/10.1007/s44162-024-00043-0

  The onset of neurological symptoms in individuals with NPD-C typically commences around eight to nine months of age, becoming more pronounced and discernible by the age of 1 to 2 years. Children diagnosed with NPD-C in the late infantile period typically face a challenging prognosis, with overall survival rarely extending beyond 6 years. This group of patients is characterized by the initial manifestation of hepatosplenomegaly, alongside the subtle yet significant presentation of early downward gaze palsy, a symptom that may not be easily detected during the early stages. As the disease progresses, late infantile children may also experience ataxia, unsteady walking, and a propensity to falls. Additionally, cognitive deficits may insidiously emerge during this period, further complicating the clinical picture.

• #82 Understanding the phenotypic variability in Niemann-Pick disease type C (NPC): a need for precision medicine | npj Genomic Medicine

  https://www.nature.com/articles/s41525-023-00365-w

  The subsequent clinical course involves a loss of acquired motor skills, cognitive regression, and pronounced spasticity. In addition, patients may present with tremors, vertical supranuclear gaze palsy (VSGP), and seizures. Many children never learn to walk, and most die before age five. […] Neurological symptoms, including ataxia, dysmetria, dysarthria, and dysphagia, among others, are associated with neurodegeneration, especially in the cerebellum, due to extensive and progressive Purkinje and cortical neuronal death, followed by hippocampal and autonomic nuclei dysfunction. […] Patients can show clumsiness due to ataxia, gait disturbance, frequent falls, VSGP (vertical supranuclear gaze palsy, usually present but often unrecognized), fine motor skill impairments, speech delay, and epilepsy. As patients age, motor problems worsen, and they develop dysphagia, dysarthria, and dementia. Most patients with this form survive between 7 to 12 years of age.

• #83

  https://link.springer.com/article/10.1007/s44162-024-00043-0

  The onset of neurological symptoms in individuals with NPD-C typically commences around eight to nine months of age, becoming more pronounced and discernible by the age of 1 to 2 years. Children diagnosed with NPD-C in the late infantile period typically face a challenging prognosis, with overall survival rarely extending beyond 6 years. This group of patients is characterized by the initial manifestation of hepatosplenomegaly, alongside the subtle yet significant presentation of early downward gaze palsy, a symptom that may not be easily detected during the early stages. As the disease progresses, late infantile children may also experience ataxia, unsteady walking, and a propensity to falls. Additionally, cognitive deficits may insidiously emerge during this period, further complicating the clinical picture.

• #84 Understanding the phenotypic variability in Niemann-Pick disease type C (NPC): a need for precision medicine | npj Genomic Medicine

  https://www.nature.com/articles/s41525-023-00365-w

  The subsequent clinical course involves a loss of acquired motor skills, cognitive regression, and pronounced spasticity. In addition, patients may present with tremors, vertical supranuclear gaze palsy (VSGP), and seizures. Many children never learn to walk, and most die before age five. […] Neurological symptoms, including ataxia, dysmetria, dysarthria, and dysphagia, among others, are associated with neurodegeneration, especially in the cerebellum, due to extensive and progressive Purkinje and cortical neuronal death, followed by hippocampal and autonomic nuclei dysfunction. […] Patients can show clumsiness due to ataxia, gait disturbance, frequent falls, VSGP (vertical supranuclear gaze palsy, usually present but often unrecognized), fine motor skill impairments, speech delay, and epilepsy. As patients age, motor problems worsen, and they develop dysphagia, dysarthria, and dementia. Most patients with this form survive between 7 to 12 years of age.

• #85 Understanding the phenotypic variability in Niemann-Pick disease type C (NPC): a need for precision medicine | npj Genomic Medicine

  https://www.nature.com/articles/s41525-023-00365-w

  The subsequent clinical course involves a loss of acquired motor skills, cognitive regression, and pronounced spasticity. In addition, patients may present with tremors, vertical supranuclear gaze palsy (VSGP), and seizures. Many children never learn to walk, and most die before age five. […] Neurological symptoms, including ataxia, dysmetria, dysarthria, and dysphagia, among others, are associated with neurodegeneration, especially in the cerebellum, due to extensive and progressive Purkinje and cortical neuronal death, followed by hippocampal and autonomic nuclei dysfunction. […] Patients can show clumsiness due to ataxia, gait disturbance, frequent falls, VSGP (vertical supranuclear gaze palsy, usually present but often unrecognized), fine motor skill impairments, speech delay, and epilepsy. As patients age, motor problems worsen, and they develop dysphagia, dysarthria, and dementia. Most patients with this form survive between 7 to 12 years of age.

• #86 Niemann-Pick Disease Type C – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK1296/

  The classic presentation of NPC is in middle-to-late childhood, with clumsiness and gait disturbance that eventually become frank ataxia. Many observant parents are aware of impaired vertical gaze, which is an early manifestation. VSGP first manifests as increased latency in initiation of vertical saccades, after which saccadic velocity gradually slows and is eventually lost. In late stages of the illness, horizontal saccades are also impaired. The physical manifestations are accompanied by insidiously progressive cognitive impairment, often mistaken at first for simple learning disability. Some children are thought to have primary behavioral disturbances, reflecting unrecognized dyspraxia in some instances. As the disease progresses, it becomes clear that the child is mentally deteriorating.

• #87

  https://omim.org/entry/257220

  Adult-onset forms, with insidious onset and slower progression, have also been reported. […] The average age of diagnosis was 10.4 years, with one-half of patients being diagnosed before the age of 6.9 years, and the average age of death was 16.2 years, with one-half of all patients dying before the age of 12.5 years. […] Common developmental difficulties included clumsiness (87%), learning difficulties (87%), ataxia (83%), dysphagia (80%), and vertical gaze palsy (81%). […] As the disease progresses, dystonia and seizures may occur. […] The characteristic ocular abnormality (supranuclear gaze palsy) usually appears early in the course of the disease but can be very subtle initially and only detected by detailed ophthalmologic assessment.

• #88 Understanding the phenotypic variability in Niemann-Pick disease type C (NPC): a need for precision medicine | npj Genomic Medicine

  https://www.nature.com/articles/s41525-023-00365-w

  This is the second most frequent form of the disease. The first sign is splenomegaly and, less commonly, hepatosplenomegaly, which also may be detected earlier (including the neonatal period). These patients suffer a significant motor impairment and a variable cognitive decline. […] Adolescent and adult-onset NPC patients may represent up to a third of all NPC patients. This group may encompass a broad array of time to symptom onset/rate of disease progression. Neurological manifestations frequently occur in these patients. The typical presentation is a history of severe progressive ataxia, dystonia, VSGP, variable cognitive decline, and psychotic symptoms. […] The psychiatric symptoms include paranoid delusions, auditory or visual hallucinations, and interpretative thoughts. Other mental manifestations include depression, behavioral problems with aggressiveness, and social isolation. Several cases have also been reported with bipolar disorder and obsessive-compulsive.

• #89 Niemann-Pick Disease Type C – Norton & Elaine Sarnoff Center for Jewish Genetics

  https://www.jewishgenetics.org/genetic-disorders/search-genetic-disorders/niemann-pick-disease-type-c/

  The first sign of this disease can show up at any age, from babies to adults, and it might include a swollen liver, a bigger spleen, or yellowing of the skin (jaundice). […] Symptoms might include sudden muscle issues like seizures, being clumsy, shaking, trouble walking, sudden falls, slurred speech, and difficulty moving the eyes up and down. […] As the disease gets worse, these kids might have trouble learning, face mental health problems, or even experience memory loss, eventually losing the ability to talk. […] In the later stages, people with Niemann-Pick disease type C might lose the ability to move their face muscles or swallow, needing a tube for feeding through the stomach. […] For those diagnosed during childhood, the disease is often fatal in the late teens or twenties because of pneumonia. […] People diagnosed in adulthood generally survive for 10 to 20 years after diagnosis.

• #90 Understanding the phenotypic variability in Niemann-Pick disease type C (NPC): a need for precision medicine | npj Genomic Medicine

  https://www.nature.com/articles/s41525-023-00365-w

  This is the second most frequent form of the disease. The first sign is splenomegaly and, less commonly, hepatosplenomegaly, which also may be detected earlier (including the neonatal period). These patients suffer a significant motor impairment and a variable cognitive decline. […] Adolescent and adult-onset NPC patients may represent up to a third of all NPC patients. This group may encompass a broad array of time to symptom onset/rate of disease progression. Neurological manifestations frequently occur in these patients. The typical presentation is a history of severe progressive ataxia, dystonia, VSGP, variable cognitive decline, and psychotic symptoms. […] The psychiatric symptoms include paranoid delusions, auditory or visual hallucinations, and interpretative thoughts. Other mental manifestations include depression, behavioral problems with aggressiveness, and social isolation. Several cases have also been reported with bipolar disorder and obsessive-compulsive.

• #91 Understanding the phenotypic variability in Niemann-Pick disease type C (NPC): a need for precision medicine | npj Genomic Medicine

  https://www.nature.com/articles/s41525-023-00365-w

  This is the second most frequent form of the disease. The first sign is splenomegaly and, less commonly, hepatosplenomegaly, which also may be detected earlier (including the neonatal period). These patients suffer a significant motor impairment and a variable cognitive decline. […] Adolescent and adult-onset NPC patients may represent up to a third of all NPC patients. This group may encompass a broad array of time to symptom onset/rate of disease progression. Neurological manifestations frequently occur in these patients. The typical presentation is a history of severe progressive ataxia, dystonia, VSGP, variable cognitive decline, and psychotic symptoms. […] The psychiatric symptoms include paranoid delusions, auditory or visual hallucinations, and interpretative thoughts. Other mental manifestations include depression, behavioral problems with aggressiveness, and social isolation. Several cases have also been reported with bipolar disorder and obsessive-compulsive.

• #92 Niemann-Pick Disease Type C: Symptoms, Causes, Treatment

  https://www.healthline.com/health/niemann-pick-disease-type-c

  Along with neurological symptoms that can onset during childhood, adults may also have: early onset dementia, psychiatric disorders like treatment-resistant depression, schizophrenia, bipolar disorder. […] The outlook for people with NPD type C varies depending on when your symptoms occur. The chances of survival are very poor if symptoms develop in infancy. If it develops after the age of 5 years old, people may live to be older than 20 years old. […] Some children develop severe, life threatening complications early, and others have mild symptoms that remain undiagnosed into adulthood. Life expectancy can range anywhere from a few days to over 60 years but is most commonly between 10-25 years of age. […] Currently, NPD type C has no cure, and treatment is largely supportive. People with the disease generally have a better outlook when symptoms develop when they’re at an older age.

• #93 Niemann-Pick Disease Type C – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK1296/

  Adolescents or adults may present with neurologic disease as described in the preceding section, albeit with a much slower rate of progression. The author has seen one individual who survived into the seventh decade, having first developed symptoms 25 years earlier. Older individuals may also present with apparent psychiatric illness, sometimes appearing to have major depression or schizophrenia. The psychiatric manifestations may overshadow neurologic signs, although the latter can usually be detected with careful examination.

• #94 Understanding the phenotypic variability in Niemann-Pick disease type C (NPC): a need for precision medicine | npj Genomic Medicine

  https://www.nature.com/articles/s41525-023-00365-w

  Niemann-Pick type C (NPC) disease is a lysosomal storage disease (LSD) characterized by the buildup of endo-lysosomal cholesterol and glycosphingolipids due to loss of function mutations in the NPC1 and NPC2 genes. NPC patients can present with a broad phenotypic spectrum, with differences at the age of onset, rate of progression, severity, organs involved, effects on the central nervous system, and even response to pharmacological treatments. […] Clinical presentations of NPC disease are highly heterogeneous and vary from a rapidly progressing neonatal form to an adult-onset chronic neurodegenerative condition. The life expectancy of the patients ranges from a few days until over 60 years of age, but most patients survive to 10-25 years of age, although probably this is an underestimation.

• #95 Orphanet: Niemann-Pick disease type C

  https://www.orpha.net/en/disease/detail/646

  Lifespan varies from a few days (in case of fetal hydrops) to a few decades. Death in early infancy can be due to either liver failure or severe pulmonary insufficiency (usually before 3-6 months). Early infantile, severe, neurological onset is often fatal between 3-5 years of age, late-infantile neurologic onset typically between 7-12, and juvenile neurologic onset between adolescence and 30 years of age.

• #96 Niemann–Pick disease – Wikipedia

  https://en.wikipedia.org/wiki/Niemann%E2%80%93Pick_disease

  Symptoms are related to the organs in which sphingomyelin accumulates. Enlargement of the liver and spleen (hepatosplenomegaly) may cause reduced appetite, abdominal distension, and pain. Enlargement of the spleen (splenomegaly) may also cause low levels of platelets in the blood (thrombocytopenia). […] Accumulation of sphingomyelin in the central nervous system (including the cerebellum) results in unsteady gait (ataxia), slurring of speech (dysarthria), and difficulty swallowing (dysphagia). Basal ganglia dysfunction causes abnormal posturing of the limbs, trunk, and face (dystonia). Upper brainstem disease results in impaired voluntary rapid eye movements (supranuclear gaze palsy). More widespread disease involving the cerebral cortex and subcortical structures causes gradual loss of intellectual abilities, causing dementia and seizures.

• #97

  https://omim.org/entry/257220

  Niemann-Pick disease type C has a highly variable clinical phenotype. […] Patients with the 'classic’ childhood onset type C usually appear normal for 1 or 2 years with symptoms appearing between 2 and 4 years. […] They gradually develop neurologic abnormalities which are initially manifested by ataxia, grand mal seizures, and loss of previously learned speech. […] Spasticity is striking and seizures, particularly myoclonic jerks, are common. […] Other features include dystonia, vertical supranuclear gaze palsy, dementia, and psychiatric manifestations. […] In general, hepatosplenomegaly is less striking than in types A and B, although it can be lethal in some. […] Cholestatic jaundice occurs in some patients. […] In the childhood-onset form, death usually occurs at age 5 to 15.

• #98 Sphingomyelinase Deficiency Clinical Presentation: History, Physical Examination

  https://emedicine.medscape.com/article/951564-clinical

  The clinical presentation and course of NPD type A is relatively uniform and is characterized by normal appearance at birth. Some patients may have neonatal edema, and hydrops fetalis may occur. The first sign detected is usually the presence of hepatosplenomegaly, which is evident at age 3 months and becomes progressively greater. The liver is usually enlarged out of proportion to the spleen. […] The patient’s development seems to progress normally until about age 6 months, followed by a plateau phase from 6 months until about age 15 months. Lastly, rapidly progressive psychomotor and intellectual deterioration occur. Psychomotor development does not progress beyond the 12-month level, and in later stages, the affected child is completely unable to interact with his/her environment. […] Mild hypotonia may be evident by age 6 months, followed by progressive loss of tone and deep tendon reflexes. With disease progression, loss of motor function occurs, and in the final stages, spasticity and rigidity are evident.

• #99 Niemann-Pick Disease | EBSCO Research Starters

  https://www.ebsco.com/research-starters/health-and-medicine/niemann-pick-disease

  Patients are emaciated, jaundiced, and have swollen abdomens and cherry-red spots in the macular region of the eye. […] Type B, or juvenile nonneuropathic NPD, is also common. Enlarged abdominal organs develop as quickly as in type A, but no neurological impairment occurs. […] Lungs are often so damaged that frequent breathlessness occurs. […] Type C, a rarer chronic form, is for approximately two years. Symptoms then develop gradually, accompanied by lost speech and motor coordination and epilepsy. […] The predominant lipid accumulant is sphingomyelin, made of fatty acids joined to substances called sphingosine and phosphocholine. […] The liver of a type A patient is usually about 50 percent larger than normal, while the liver of a type B patient grows so large that it deforms and causes abdominal pain. […] However, the life expectancy of patients with NPD has not been prolonged much.

• #100 Niemann-Pick disease type C | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-5-16

  The clinical presentation of NP-C is extremely heterogeneous, with an age of onset ranging from the perinatal period until well into adult age (as late as the seventh decade of life). Similarly, the lifespan of the patients varies between a few days until over 60 years of age, although a majority of cases die between 10 and 25 years of age. […] Importantly, visceral involvement (of liver, spleen, and sometimes lung) and neurologic or psychiatric manifestations arise at different times, and they also follow completely independent courses. Apart from a small subset of patients who die at birth, or in the first 6 months of life from hepatic or respiratory failure, and exceptional adult cases, all patients ultimately will develop a progressive and fatal neurological disease. […] In typical patients, the neurologic disorder consists mainly of cerebellar ataxia, dysarthria, dysphagia, and progressive dementia, and the majority of cases show a characteristic vertical supranuclear gaze palsy (VSGP). Cataplexy, seizures, and dystonia are other quite common features, and psychiatric disturbances are frequent in late-onset patients.

• #101 The Genetic Basis, Lung Involvement, and Therapeutic Options in Niemann–Pick Disease: A Comprehensive Review

  https://www.mdpi.com/2218-273X/14/2/211

  Hepatomegaly is caused by the accumulation of the lipid-laden macrophages in the reticuloendothelial system of the liver. It can cause liver dysfunction, leading to cirrhosis and hepatic failure in some cases. Hepatic involvement, together with lung involvement, represents the most common cause of death in NPD type B. […] Respiratory complications may occur in all three types of Niemann–Pick Disease, with type B being the most common. Pulmonary complications are uncommon in NPD type A, and they usually consist of recurrent respiratory infections, interstitial lung disease, and aspiration pneumonia. […] Patients with NPD type A typically succumb to respiratory failure by the age of 3. In contrast, patients with NPD type B exhibit a more diverse clinical phenotype and life expectancy. […] Specific lung manifestations have been described in NPD type B, including interstitial lung disease (ILD), pulmonary hypertension, alveolar hypoventilation, upper airway obstruction (with or without obstructive sleep apnea syndrome), and recurrent airway infections caused by mucous membrane swelling.

• #102

  https://omim.org/entry/257220

  Niemann-Pick disease type C has a highly variable clinical phenotype. […] Patients with the 'classic’ childhood onset type C usually appear normal for 1 or 2 years with symptoms appearing between 2 and 4 years. […] They gradually develop neurologic abnormalities which are initially manifested by ataxia, grand mal seizures, and loss of previously learned speech. […] Spasticity is striking and seizures, particularly myoclonic jerks, are common. […] Other features include dystonia, vertical supranuclear gaze palsy, dementia, and psychiatric manifestations. […] In general, hepatosplenomegaly is less striking than in types A and B, although it can be lethal in some. […] Cholestatic jaundice occurs in some patients. […] In the childhood-onset form, death usually occurs at age 5 to 15.

• #103 Niemann–Pick disease – Wikipedia

  https://en.wikipedia.org/wiki/Niemann%E2%80%93Pick_disease

  Symptoms are related to the organs in which sphingomyelin accumulates. Enlargement of the liver and spleen (hepatosplenomegaly) may cause reduced appetite, abdominal distension, and pain. Enlargement of the spleen (splenomegaly) may also cause low levels of platelets in the blood (thrombocytopenia). […] Accumulation of sphingomyelin in the central nervous system (including the cerebellum) results in unsteady gait (ataxia), slurring of speech (dysarthria), and difficulty swallowing (dysphagia). Basal ganglia dysfunction causes abnormal posturing of the limbs, trunk, and face (dystonia). Upper brainstem disease results in impaired voluntary rapid eye movements (supranuclear gaze palsy). More widespread disease involving the cerebral cortex and subcortical structures causes gradual loss of intellectual abilities, causing dementia and seizures.

• #104 Niemann-Pick disease type C | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-5-16

  The clinical presentation of NP-C is extremely heterogeneous, with an age of onset ranging from the perinatal period until well into adult age (as late as the seventh decade of life). Similarly, the lifespan of the patients varies between a few days until over 60 years of age, although a majority of cases die between 10 and 25 years of age. […] Importantly, visceral involvement (of liver, spleen, and sometimes lung) and neurologic or psychiatric manifestations arise at different times, and they also follow completely independent courses. Apart from a small subset of patients who die at birth, or in the first 6 months of life from hepatic or respiratory failure, and exceptional adult cases, all patients ultimately will develop a progressive and fatal neurological disease. […] In typical patients, the neurologic disorder consists mainly of cerebellar ataxia, dysarthria, dysphagia, and progressive dementia, and the majority of cases show a characteristic vertical supranuclear gaze palsy (VSGP). Cataplexy, seizures, and dystonia are other quite common features, and psychiatric disturbances are frequent in late-onset patients.

• #105 ASMD Niemann-Pick Disease Type B – NPUK

  https://www.npuk.org/niemann-pick-diseases/asmd-np-b/

  The first symptoms of Niemann-Pick disease Type B (NPB) are usually an enlarged liver and/or spleen in early childhood. […] Symptoms can include: A progressive enlargement of organs, Poor growth, Susceptibility to respiratory infections, Bleeding problems, Bone pain, Increased stress on the heart. […] There is usually no neurological involvement in NPB. Most patients will survive into adulthood, but not without experiencing health problems.

• #106 Niemann-Pick disease type C symptomatology: an expert-based clinical description | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-8-166

  While visceral manifestations tend to predominate during the perinatal and infantile period (2 months-6 years of age), neurological and psychiatric involvement is more prominent during the juvenile/adult period (6 years of age). […] Progressive cognitive decline, which always occurs in patients with NP-C, manifests as memory and executive impairment in juvenile/adult patients. […] Disease prognosis mainly correlates with the age at onset of the neurological signs, with early-onset forms progressing faster. […] Therefore, a detailed and descriptive picture of NP-C signs and symptoms may help improve disease detection and early diagnosis, so that therapy with miglustat (Zavesca), the only available treatment approved to date, can be started as soon as neurological symptoms appear, in order to slow disease progression.

• #107 Sphingomyelinase Deficiency Clinical Presentation: History, Physical Examination

  https://emedicine.medscape.com/article/951564-clinical

  The clinical presentation and course of NPD type A is relatively uniform and is characterized by normal appearance at birth. Some patients may have neonatal edema, and hydrops fetalis may occur. The first sign detected is usually the presence of hepatosplenomegaly, which is evident at age 3 months and becomes progressively greater. The liver is usually enlarged out of proportion to the spleen. […] The patient’s development seems to progress normally until about age 6 months, followed by a plateau phase from 6 months until about age 15 months. Lastly, rapidly progressive psychomotor and intellectual deterioration occur. Psychomotor development does not progress beyond the 12-month level, and in later stages, the affected child is completely unable to interact with his/her environment. […] Mild hypotonia may be evident by age 6 months, followed by progressive loss of tone and deep tendon reflexes. With disease progression, loss of motor function occurs, and in the final stages, spasticity and rigidity are evident.

• #108 Niemann-Pick disease type C | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-5-16

  The clinical presentation of NP-C is extremely heterogeneous, with an age of onset ranging from the perinatal period until well into adult age (as late as the seventh decade of life). Similarly, the lifespan of the patients varies between a few days until over 60 years of age, although a majority of cases die between 10 and 25 years of age. […] Importantly, visceral involvement (of liver, spleen, and sometimes lung) and neurologic or psychiatric manifestations arise at different times, and they also follow completely independent courses. Apart from a small subset of patients who die at birth, or in the first 6 months of life from hepatic or respiratory failure, and exceptional adult cases, all patients ultimately will develop a progressive and fatal neurological disease. […] In typical patients, the neurologic disorder consists mainly of cerebellar ataxia, dysarthria, dysphagia, and progressive dementia, and the majority of cases show a characteristic vertical supranuclear gaze palsy (VSGP). Cataplexy, seizures, and dystonia are other quite common features, and psychiatric disturbances are frequent in late-onset patients.

• #109 Niemann-Pick Disease Type C – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK1296/

  The classic presentation of NPC is in middle-to-late childhood, with clumsiness and gait disturbance that eventually become frank ataxia. Many observant parents are aware of impaired vertical gaze, which is an early manifestation. VSGP first manifests as increased latency in initiation of vertical saccades, after which saccadic velocity gradually slows and is eventually lost. In late stages of the illness, horizontal saccades are also impaired. The physical manifestations are accompanied by insidiously progressive cognitive impairment, often mistaken at first for simple learning disability. Some children are thought to have primary behavioral disturbances, reflecting unrecognized dyspraxia in some instances. As the disease progresses, it becomes clear that the child is mentally deteriorating.

• #110 Niemann-Pick Disease Type C – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK1296/

  The classic presentation of NPC is in middle-to-late childhood, with clumsiness and gait disturbance that eventually become frank ataxia. Many observant parents are aware of impaired vertical gaze, which is an early manifestation. VSGP first manifests as increased latency in initiation of vertical saccades, after which saccadic velocity gradually slows and is eventually lost. In late stages of the illness, horizontal saccades are also impaired. The physical manifestations are accompanied by insidiously progressive cognitive impairment, often mistaken at first for simple learning disability. Some children are thought to have primary behavioral disturbances, reflecting unrecognized dyspraxia in some instances. As the disease progresses, it becomes clear that the child is mentally deteriorating.

• #111 Niemann-Pick disease type C | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-5-16

  The clinical presentation of NP-C is extremely heterogeneous, with an age of onset ranging from the perinatal period until well into adult age (as late as the seventh decade of life). Similarly, the lifespan of the patients varies between a few days until over 60 years of age, although a majority of cases die between 10 and 25 years of age. […] Importantly, visceral involvement (of liver, spleen, and sometimes lung) and neurologic or psychiatric manifestations arise at different times, and they also follow completely independent courses. Apart from a small subset of patients who die at birth, or in the first 6 months of life from hepatic or respiratory failure, and exceptional adult cases, all patients ultimately will develop a progressive and fatal neurological disease. […] In typical patients, the neurologic disorder consists mainly of cerebellar ataxia, dysarthria, dysphagia, and progressive dementia, and the majority of cases show a characteristic vertical supranuclear gaze palsy (VSGP). Cataplexy, seizures, and dystonia are other quite common features, and psychiatric disturbances are frequent in late-onset patients.

• #112

  https://omim.org/entry/257220

  Niemann-Pick disease type C has a highly variable clinical phenotype. […] Patients with the 'classic’ childhood onset type C usually appear normal for 1 or 2 years with symptoms appearing between 2 and 4 years. […] They gradually develop neurologic abnormalities which are initially manifested by ataxia, grand mal seizures, and loss of previously learned speech. […] Spasticity is striking and seizures, particularly myoclonic jerks, are common. […] Other features include dystonia, vertical supranuclear gaze palsy, dementia, and psychiatric manifestations. […] In general, hepatosplenomegaly is less striking than in types A and B, although it can be lethal in some. […] Cholestatic jaundice occurs in some patients. […] In the childhood-onset form, death usually occurs at age 5 to 15.

• #113 Niemann-Pick Disease Type C (NPC) – Rare Awareness Rare Education

  https://rareportal.org.au/rare-disease/niemann-pick-disease-type-c-npc/

  Niemann-Pick disease type C (NPC) is a type of lysosomal storage disorder (under the class of sphingolipidosis). In NPC, cells in the body are unable to properly transport cholesterol and other fatty substances (lipids), resulting in their accumulation. NPC is considered to be a childhood dementia disorder, characterised by progressive brain damage (neurodegeneration). Symptoms can be highly variable between individuals and can develop at any age of life. In some cases, NPC can be life-threatening in the first few months of life, whilst for other individuals, symptoms may not be obvious until adulthood. […] The disease presentation of Niemann-Pick disease type C (NPC) is highly variable between individuals and can change over an individuals lifetime. Babies may present with jaundice, poor muscle tone (hypotonia), enlarged liver and spleen (hepatosplenomegaly), as well as liver and lung disease that can lead to life-threatening complications. Neurological symptoms often emerge in childhood, but in some cases, do not present until adulthood. Symptoms are often progressive and may include: Difficulty in controlling and posturing of limbs (dystonia), Loss of muscle control leading to lack of balance, coordination and trouble walking (ataxia) this may present as unsteadiness of gait and clumsiness, Weakness of speech muscles, resulting in slurred or slow and unclear speech (dysarthria), Difficulty in swallowing (dysphagia); assisted feeding may be required in some cases, Difficulty with upward and downward eye movements (Vertical Supranuclear Gaze Palsy, VSGP), Generalised loss of muscle tone whilst still conscious, triggered by laughing (gelastic cataplexy), Seizures, Learning difficulties (cognitive dysfunction) and progressive intellectual decline (dementia), Psychiatric disturbances, particularly in adults. […] Individuals with NPC may also be at risk of aspiration pneumonia, which can be life-threatening. It is an infection of the lungs caused by inhaling saliva, food, or liquid into the airway, which can be due to the inability to swallow.

• #114

  https://omim.org/entry/257220

  Adult-onset forms, with insidious onset and slower progression, have also been reported. […] The average age of diagnosis was 10.4 years, with one-half of patients being diagnosed before the age of 6.9 years, and the average age of death was 16.2 years, with one-half of all patients dying before the age of 12.5 years. […] Common developmental difficulties included clumsiness (87%), learning difficulties (87%), ataxia (83%), dysphagia (80%), and vertical gaze palsy (81%). […] As the disease progresses, dystonia and seizures may occur. […] The characteristic ocular abnormality (supranuclear gaze palsy) usually appears early in the course of the disease but can be very subtle initially and only detected by detailed ophthalmologic assessment.

• #115 Niemann-Pick disease type C | Alzheimer’s Society

  https://www.alzheimers.org.uk/about-dementia/types-dementia/Niemann-Pick-disease-type-C

  Niemann-Pick disease type C is one of a group of rare inherited disorders. It mainly affects school-age children but can occur at any time, from early infancy to adulthood. This can lead to progressive loss of movement and difficulties with walking and swallowing. […] People who first show symptoms in late adolescence or early adulthood are more likely to experience dementia as part of the disease. The dementia symptoms include confusion, memory problems and difficulties in concentrating and learning.

• #116 Sphingomyelinase Deficiency Clinical Presentation: History, Physical Examination

  https://emedicine.medscape.com/article/951564-clinical

  The clinical presentation and course of NPD type A is relatively uniform and is characterized by normal appearance at birth. Some patients may have neonatal edema, and hydrops fetalis may occur. The first sign detected is usually the presence of hepatosplenomegaly, which is evident at age 3 months and becomes progressively greater. The liver is usually enlarged out of proportion to the spleen. […] The patient’s development seems to progress normally until about age 6 months, followed by a plateau phase from 6 months until about age 15 months. Lastly, rapidly progressive psychomotor and intellectual deterioration occur. Psychomotor development does not progress beyond the 12-month level, and in later stages, the affected child is completely unable to interact with his/her environment. […] Mild hypotonia may be evident by age 6 months, followed by progressive loss of tone and deep tendon reflexes. With disease progression, loss of motor function occurs, and in the final stages, spasticity and rigidity are evident.

• #117 Niemann-Pick Disease Type C – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK1296/

  The classic presentation of NPC is in middle-to-late childhood, with clumsiness and gait disturbance that eventually become frank ataxia. Many observant parents are aware of impaired vertical gaze, which is an early manifestation. VSGP first manifests as increased latency in initiation of vertical saccades, after which saccadic velocity gradually slows and is eventually lost. In late stages of the illness, horizontal saccades are also impaired. The physical manifestations are accompanied by insidiously progressive cognitive impairment, often mistaken at first for simple learning disability. Some children are thought to have primary behavioral disturbances, reflecting unrecognized dyspraxia in some instances. As the disease progresses, it becomes clear that the child is mentally deteriorating.

• #118 Understanding the phenotypic variability in Niemann-Pick disease type C (NPC): a need for precision medicine | npj Genomic Medicine

  https://www.nature.com/articles/s41525-023-00365-w

  This is the second most frequent form of the disease. The first sign is splenomegaly and, less commonly, hepatosplenomegaly, which also may be detected earlier (including the neonatal period). These patients suffer a significant motor impairment and a variable cognitive decline. […] Adolescent and adult-onset NPC patients may represent up to a third of all NPC patients. This group may encompass a broad array of time to symptom onset/rate of disease progression. Neurological manifestations frequently occur in these patients. The typical presentation is a history of severe progressive ataxia, dystonia, VSGP, variable cognitive decline, and psychotic symptoms. […] The psychiatric symptoms include paranoid delusions, auditory or visual hallucinations, and interpretative thoughts. Other mental manifestations include depression, behavioral problems with aggressiveness, and social isolation. Several cases have also been reported with bipolar disorder and obsessive-compulsive.

• #119 Niemann-Pick disease type C | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-5-16

  The clinical presentation of NP-C is extremely heterogeneous, with an age of onset ranging from the perinatal period until well into adult age (as late as the seventh decade of life). Similarly, the lifespan of the patients varies between a few days until over 60 years of age, although a majority of cases die between 10 and 25 years of age. […] Importantly, visceral involvement (of liver, spleen, and sometimes lung) and neurologic or psychiatric manifestations arise at different times, and they also follow completely independent courses. Apart from a small subset of patients who die at birth, or in the first 6 months of life from hepatic or respiratory failure, and exceptional adult cases, all patients ultimately will develop a progressive and fatal neurological disease. […] In typical patients, the neurologic disorder consists mainly of cerebellar ataxia, dysarthria, dysphagia, and progressive dementia, and the majority of cases show a characteristic vertical supranuclear gaze palsy (VSGP). Cataplexy, seizures, and dystonia are other quite common features, and psychiatric disturbances are frequent in late-onset patients.

• #120 Understanding the phenotypic variability in Niemann-Pick disease type C (NPC): a need for precision medicine | npj Genomic Medicine

  https://www.nature.com/articles/s41525-023-00365-w

  This is the second most frequent form of the disease. The first sign is splenomegaly and, less commonly, hepatosplenomegaly, which also may be detected earlier (including the neonatal period). These patients suffer a significant motor impairment and a variable cognitive decline. […] Adolescent and adult-onset NPC patients may represent up to a third of all NPC patients. This group may encompass a broad array of time to symptom onset/rate of disease progression. Neurological manifestations frequently occur in these patients. The typical presentation is a history of severe progressive ataxia, dystonia, VSGP, variable cognitive decline, and psychotic symptoms. […] The psychiatric symptoms include paranoid delusions, auditory or visual hallucinations, and interpretative thoughts. Other mental manifestations include depression, behavioral problems with aggressiveness, and social isolation. Several cases have also been reported with bipolar disorder and obsessive-compulsive.

• #121 Niemann-Pick Disease Type C – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK1296/

  Adolescents or adults may present with neurologic disease as described in the preceding section, albeit with a much slower rate of progression. The author has seen one individual who survived into the seventh decade, having first developed symptoms 25 years earlier. Older individuals may also present with apparent psychiatric illness, sometimes appearing to have major depression or schizophrenia. The psychiatric manifestations may overshadow neurologic signs, although the latter can usually be detected with careful examination.

• #122 The Genetic Basis, Lung Involvement, and Therapeutic Options in Niemann–Pick Disease: A Comprehensive Review

  https://www.mdpi.com/2218-273X/14/2/211

  Niemann–Pick Disease (NPD) is a rare autosomal recessive disease belonging to lysosomal storage disorders. […] Although all three types of NPD can manifest with pulmonary involvement, lung disease occurs more frequently in NPD type B, typically with interstitial lung disease, recurrent pulmonary infections, and respiratory failure. […] In NPD type A, macular cherry-red spots are detectable in all infants by 12 months. This term describes the ophthalmoscopic appearance of the retina in neurometabolic disorders, like Niemann–Pick Disease. The red color of the fovea (in Caucasian patients) contrasts with the surrounding retina, which is pale for the accumulation of lipids and sphingolipids in the ganglionic cells of the retina at the macula. […] NPD type B is a multisystemic disease with phenotypic heterogeneity and a variable severity and progression rate between patients. The most common clinical manifestations at onset are represented by splenomegaly and hepatomegaly.

• #123 The Genetic Basis, Lung Involvement, and Therapeutic Options in Niemann–Pick Disease: A Comprehensive Review

  https://www.mdpi.com/2218-273X/14/2/211

  The common pathogenetic process involves the accumulation of Niemann–Pick cells in the alveolar septa, bronchial walls, and pleura, leading to a progressively restrictive pattern that can be detected with pulmonary function tests. […] In conclusion, lung involvement in NPDB exhibits high heterogeneity, featuring clinical and radiological manifestations of varying severity.

• #124 Sphingomyelinase Deficiency Clinical Presentation: History, Physical Examination

  https://emedicine.medscape.com/article/951564-clinical

  Affected infants exhibit feeding problems, failure to thrive, recurrent respiratory tract infections, and irritability. Most children with NPD type A die before age 2-3 years, often from respiratory failure following pulmonary infection. […] The clinical presentation and course in patients with NPD type B disease is milder and more variable. The condition is diagnosed in most patients in infancy or childhood when enlargement of the liver, spleen, or both is detected during routine physical examination. […] At diagnosis, patients with NPD type B also have evidence of mild pulmonary involvement, usually detected as a diffuse reticular or finely nodular infiltration on chest radiograph films. […] In most patients with NPD type B, decreased pulmonary diffusion caused by storage of sphingomyelin in pulmonary macrophages becomes evident in childhood and progresses with age. Severely affected individuals may experience significant pulmonary compromise by age 15-20 years. Such patients have low partial pressure of oxygen (PO2) values and dyspnea on exertion.

• #125 Sphingomyelinase Deficiency Clinical Presentation: History, Physical Examination

  https://emedicine.medscape.com/article/951564-clinical

  Affected infants exhibit feeding problems, failure to thrive, recurrent respiratory tract infections, and irritability. Most children with NPD type A die before age 2-3 years, often from respiratory failure following pulmonary infection. […] The clinical presentation and course in patients with NPD type B disease is milder and more variable. The condition is diagnosed in most patients in infancy or childhood when enlargement of the liver, spleen, or both is detected during routine physical examination. […] At diagnosis, patients with NPD type B also have evidence of mild pulmonary involvement, usually detected as a diffuse reticular or finely nodular infiltration on chest radiograph films. […] In most patients with NPD type B, decreased pulmonary diffusion caused by storage of sphingomyelin in pulmonary macrophages becomes evident in childhood and progresses with age. Severely affected individuals may experience significant pulmonary compromise by age 15-20 years. Such patients have low partial pressure of oxygen (PO2) values and dyspnea on exertion.

• #126 The Genetic Basis, Lung Involvement, and Therapeutic Options in Niemann–Pick Disease: A Comprehensive Review

  https://www.mdpi.com/2218-273X/14/2/211

  Hepatomegaly is caused by the accumulation of the lipid-laden macrophages in the reticuloendothelial system of the liver. It can cause liver dysfunction, leading to cirrhosis and hepatic failure in some cases. Hepatic involvement, together with lung involvement, represents the most common cause of death in NPD type B. […] Respiratory complications may occur in all three types of Niemann–Pick Disease, with type B being the most common. Pulmonary complications are uncommon in NPD type A, and they usually consist of recurrent respiratory infections, interstitial lung disease, and aspiration pneumonia. […] Patients with NPD type A typically succumb to respiratory failure by the age of 3. In contrast, patients with NPD type B exhibit a more diverse clinical phenotype and life expectancy. […] Specific lung manifestations have been described in NPD type B, including interstitial lung disease (ILD), pulmonary hypertension, alveolar hypoventilation, upper airway obstruction (with or without obstructive sleep apnea syndrome), and recurrent airway infections caused by mucous membrane swelling.

• #127 Niemann-Pick Disease Type C (NPC) – Rare Awareness Rare Education

  https://rareportal.org.au/rare-disease/niemann-pick-disease-type-c-npc/

  Niemann-Pick disease type C (NPC) is a type of lysosomal storage disorder (under the class of sphingolipidosis). In NPC, cells in the body are unable to properly transport cholesterol and other fatty substances (lipids), resulting in their accumulation. NPC is considered to be a childhood dementia disorder, characterised by progressive brain damage (neurodegeneration). Symptoms can be highly variable between individuals and can develop at any age of life. In some cases, NPC can be life-threatening in the first few months of life, whilst for other individuals, symptoms may not be obvious until adulthood. […] The disease presentation of Niemann-Pick disease type C (NPC) is highly variable between individuals and can change over an individuals lifetime. Babies may present with jaundice, poor muscle tone (hypotonia), enlarged liver and spleen (hepatosplenomegaly), as well as liver and lung disease that can lead to life-threatening complications. Neurological symptoms often emerge in childhood, but in some cases, do not present until adulthood. Symptoms are often progressive and may include: Difficulty in controlling and posturing of limbs (dystonia), Loss of muscle control leading to lack of balance, coordination and trouble walking (ataxia) this may present as unsteadiness of gait and clumsiness, Weakness of speech muscles, resulting in slurred or slow and unclear speech (dysarthria), Difficulty in swallowing (dysphagia); assisted feeding may be required in some cases, Difficulty with upward and downward eye movements (Vertical Supranuclear Gaze Palsy, VSGP), Generalised loss of muscle tone whilst still conscious, triggered by laughing (gelastic cataplexy), Seizures, Learning difficulties (cognitive dysfunction) and progressive intellectual decline (dementia), Psychiatric disturbances, particularly in adults. […] Individuals with NPC may also be at risk of aspiration pneumonia, which can be life-threatening. It is an infection of the lungs caused by inhaling saliva, food, or liquid into the airway, which can be due to the inability to swallow.

• #128 Niemann-Pick Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK556129/

  Niemann-Pick disease is a progressive disease, and quite often, complications develop with time. The initial involvement of the liver can transform into fulminant hepatic failure. Deterioration of the lungs can result in respiratory insufficiency. Progressive neurodegeneration can cause dementia, seizures, and schizophrenia-like psychosis. Severe thrombocytopenia can result in internal or external bleeding. […] Type A is almost always fatal, and affected children are unlikely to live beyond 4 years of age. Type B children have a slightly better prognosis than type A and may live till late childhood or early adulthood. But they develop many complications from the disease, so the life quality is not so good. The prognosis for type C depends on the time of the initial presentation. If it affects in infancy, the chances are very poor for survival beyond 5 years of age. If it affects after 5 years, then patients may live to the age of 20 years. But each patient has a slightly different outlook depending on the severity and presentation of the disease.[15]

• #129 How Long Can You Live With Niemann–Pick Disease? Life Expectancy

  https://www.medicinenet.com/how_long_can_you_live_with_niemann%E2%80%93pick_disease/article.htm

  NiemannPick disease (NP) leads to a gradual loss of function of nerves, the brain, and other organs. […] The life expectancy for NP varies depending on the type of this disease. Prognosis is strongly related to the age at which the neurological manifestations appear and is generally poor, with affected individuals expected to live only for 10 to 20 years after diagnosis. […] People with NP have varying life expectancies. A child who exhibits NP symptoms before age one may not survive to school age. People who develop symptoms after starting school may live into their late teens, with a few surviving into their twenties. […] NiemannPick disease (NP) can damage the brain, nerves, liver, spleen, bone marrow, and, in severe instances, the lungs. People with this disorder have symptoms due to the gradual loss of function of nerves, the brain, and other organs.

• #130 Niemann-Pick Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK556129/

  Niemann-Pick disease is a progressive disease, and quite often, complications develop with time. The initial involvement of the liver can transform into fulminant hepatic failure. Deterioration of the lungs can result in respiratory insufficiency. Progressive neurodegeneration can cause dementia, seizures, and schizophrenia-like psychosis. Severe thrombocytopenia can result in internal or external bleeding. […] Type A is almost always fatal, and affected children are unlikely to live beyond 4 years of age. Type B children have a slightly better prognosis than type A and may live till late childhood or early adulthood. But they develop many complications from the disease, so the life quality is not so good. The prognosis for type C depends on the time of the initial presentation. If it affects in infancy, the chances are very poor for survival beyond 5 years of age. If it affects after 5 years, then patients may live to the age of 20 years. But each patient has a slightly different outlook depending on the severity and presentation of the disease.[15]

• #131 Niemann-Pick Disease – Pediatrics – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/pediatrics/inherited-disorders-of-metabolism/niemann-pick-disease

  Children with type A have 5% of normal sphingomyelinase activity. The disease is characterized by hepatosplenomegaly, failure to thrive, and rapidly progressive neurodegeneration. Death occurs by age 2 or 3 years. […] Patients with type B have sphingomyelinase activity within 5 to 10% of normal. Type B is more variable clinically than type A. Hepatosplenomegaly and lymphadenopathy may occur. Pancytopenia is common. Most patients with type B have little or no neurologic involvement, may have intellectual disability, and survive into adulthood; they may be clinically indistinguishable from those with type I Gaucher disease. In severe cases of type B, progressive pulmonary infiltrates cause major complications. […] Children with type C develop symptoms usually during childhood, with seizures and neurologic deterioration. Type C is always fatal, and most children die before age 20.

• #132 Niemann-Pick Disease, Types A and B | Hereditary Ocular Diseases

  https://disorders.eyes.arizona.edu/disorders/niemann-pick-disease-types-and-b

  Affected infants usually develop prominent cherry red spots during the first 12 months of life and the entire retina has an opaque appearance. […] Vision in the first year of life is likely normal as infants have normal fixation, pupillary reactions, and following movements with no nystagmus. However, by about 2 years of age visual responsiveness may be lost. […] Both the age of onset of neurological symptoms and the rate of progression are highly variable. Type A, known as the infantile form, is the more severe disease with onset by 6 months of age with rapid progression and few patients survive beyond three years of age. […] Neonates seem to develop normally for the first 6 months but then become irritable, fail to thrive and feed poorly. Hepatosplenomegaly is usually the first physical sign. Hypotonia and pulmonary infections are common. These patients never achieve normal developmental milestones such as sitting, walking or crawling and the neurodegeneration is relentless from this point with the median age at death 21 months, usually from respiratory disease. […] The less severe form of Niemann-Pick disease, type B, has a later onset and slower course. Such patients have widespread visceral disease affecting liver, spleen and lungs with hyperlipidemia but few neurologic symptoms and often survive into adulthood.

• #133 Sphingomyelinase Deficiency Clinical Presentation: History, Physical Examination

  https://emedicine.medscape.com/article/951564-clinical

  Affected infants exhibit feeding problems, failure to thrive, recurrent respiratory tract infections, and irritability. Most children with NPD type A die before age 2-3 years, often from respiratory failure following pulmonary infection. […] The clinical presentation and course in patients with NPD type B disease is milder and more variable. The condition is diagnosed in most patients in infancy or childhood when enlargement of the liver, spleen, or both is detected during routine physical examination. […] At diagnosis, patients with NPD type B also have evidence of mild pulmonary involvement, usually detected as a diffuse reticular or finely nodular infiltration on chest radiograph films. […] In most patients with NPD type B, decreased pulmonary diffusion caused by storage of sphingomyelin in pulmonary macrophages becomes evident in childhood and progresses with age. Severely affected individuals may experience significant pulmonary compromise by age 15-20 years. Such patients have low partial pressure of oxygen (PO2) values and dyspnea on exertion.

• #134 Niemann-Pick Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK556129/

  Niemann-Pick disease is a progressive disease, and quite often, complications develop with time. The initial involvement of the liver can transform into fulminant hepatic failure. Deterioration of the lungs can result in respiratory insufficiency. Progressive neurodegeneration can cause dementia, seizures, and schizophrenia-like psychosis. Severe thrombocytopenia can result in internal or external bleeding. […] Type A is almost always fatal, and affected children are unlikely to live beyond 4 years of age. Type B children have a slightly better prognosis than type A and may live till late childhood or early adulthood. But they develop many complications from the disease, so the life quality is not so good. The prognosis for type C depends on the time of the initial presentation. If it affects in infancy, the chances are very poor for survival beyond 5 years of age. If it affects after 5 years, then patients may live to the age of 20 years. But each patient has a slightly different outlook depending on the severity and presentation of the disease.[15]

• #135 Niemann-Pick Disease | Baby’s First Test | Newborn Screening | Baby Health

  https://babysfirsttest.org/newborn-screening/conditions/niemann-pick-disease

  Niemann-Pick disease type B (NPD-B) is generally associated with milder symptoms and a longer lifespan. In fact, individuals with this form of the condition usually live into adulthood, though they may have many health complications. […] Early detection and proper treatment can help improve the quality of life in babies with NPD-A and the long term outcome of babies with NPD-B. This is why newborn screening for NPD is so important.

• #136 First therapy to treat two types of Niemann-Pick disease, a rare genetic metabolic disorder | European Medicines Agency (EMA)

  https://www.ema.europa.eu/en/news/first-therapy-treat-two-types-niemann-pick-disease-rare-genetic-metabolic-disorder

  Historically referred to as Niemann-Pick disease types A (NPD A) and B (NPD B), ASMD is a genetic disorder. […] ASMD is seriously debilitating and life threatening since the build-up of fatty substances can cause brain damage and swelling of organs such as liver and spleen. […] Patients receive only palliative and supportive care to manage the symptoms. As a result, morbidity and mortality are high, especially in children. The most common causes of death are respiratory disease, liver problems and complications due to the excessive size of multiple organs. Children with type A ASMD usually die before their third birthday. The median life expectancy for type B patients is 17 years. […] The adverse events of Xenpozyme were generally mild to moderate and, in most cases, manageable. The majority were related to infections, infusion-related reactions, or gastro-intestinal complaints (disease signs and symptoms in children).

• #137 Niemann-Pick Disease | Causes, signs, symptoms & treatment

  https://cpdonline.co.uk/knowledge-base/care/niemann-pick-disease/

  For those with type B, survival is possible until adolescence or even early adulthood. There are often problems with complications, however, that make life very difficult in the latter stages of the disease. This includes problems due to having an enlarged spleen or liver and respiratory failure. […] Individuals with type C NPD can have a longer lifespan but the disease is still fatal. The life expectancy of someone with type C will be determined by the age at onset of symptoms. If the symptoms appear early and in infancy, the child will be unlikely to reach age five. However, if symptoms arent present until after the age of five, the individual could live until around age 20.

• #138 First therapy to treat two types of Niemann-Pick disease, a rare genetic metabolic disorder | European Medicines Agency (EMA)

  https://www.ema.europa.eu/en/news/first-therapy-treat-two-types-niemann-pick-disease-rare-genetic-metabolic-disorder

  Historically referred to as Niemann-Pick disease types A (NPD A) and B (NPD B), ASMD is a genetic disorder. […] ASMD is seriously debilitating and life threatening since the build-up of fatty substances can cause brain damage and swelling of organs such as liver and spleen. […] Patients receive only palliative and supportive care to manage the symptoms. As a result, morbidity and mortality are high, especially in children. The most common causes of death are respiratory disease, liver problems and complications due to the excessive size of multiple organs. Children with type A ASMD usually die before their third birthday. The median life expectancy for type B patients is 17 years. […] The adverse events of Xenpozyme were generally mild to moderate and, in most cases, manageable. The majority were related to infections, infusion-related reactions, or gastro-intestinal complaints (disease signs and symptoms in children).

• #139 Niemann-Pick disease type C | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-5-16

  The age of onset of the systemic symptoms is not related with that of the neurological disease (the latter can occur many years or even decades later), while there is a correlation between the age of onset of the neurological symptoms and the general further course of the disease and lifespan. […] Patients with the severe neurologic early infantile form often die between 3 and 5 years of age, those with a late-infantile neurologic onset usually between 7 and 12. Patients with a juvenile neurologic onset survive until adolescence or later, with a sizable proportion reaching the age of 30. In a review of 68 cases with adult onset, the mean age at death (on 20 patients) was 38 10.2 years, but some patients have reached the age of 70.

• #140 Orphanet: Niemann-Pick disease type C

  https://www.orpha.net/en/disease/detail/646

  Lifespan varies from a few days (in case of fetal hydrops) to a few decades. Death in early infancy can be due to either liver failure or severe pulmonary insufficiency (usually before 3-6 months). Early infantile, severe, neurological onset is often fatal between 3-5 years of age, late-infantile neurologic onset typically between 7-12, and juvenile neurologic onset between adolescence and 30 years of age.

• #141 Niemann-Pick Disease | Causes, signs, symptoms & treatment

  https://cpdonline.co.uk/knowledge-base/care/niemann-pick-disease/

  For those with type B, survival is possible until adolescence or even early adulthood. There are often problems with complications, however, that make life very difficult in the latter stages of the disease. This includes problems due to having an enlarged spleen or liver and respiratory failure. […] Individuals with type C NPD can have a longer lifespan but the disease is still fatal. The life expectancy of someone with type C will be determined by the age at onset of symptoms. If the symptoms appear early and in infancy, the child will be unlikely to reach age five. However, if symptoms arent present until after the age of five, the individual could live until around age 20.

• #142 FDA Approves First Treatment for Niemann-Pick Disease, Type C | FDA

  https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-niemann-pick-disease-type-c

  NPC is a rare genetic disease that results in progressive neurological symptoms and organ dysfunction. […] On average, individuals affected by this devastating disease only live for about 13 years. […] Miplyffa resulted in a slower disease progression as measured by the R4DNPCCSS score.

• #143 Niemann-Pick Disease Type C – Norton & Elaine Sarnoff Center for Jewish Genetics

  https://www.jewishgenetics.org/genetic-disorders/search-genetic-disorders/niemann-pick-disease-type-c/

  The first sign of this disease can show up at any age, from babies to adults, and it might include a swollen liver, a bigger spleen, or yellowing of the skin (jaundice). […] Symptoms might include sudden muscle issues like seizures, being clumsy, shaking, trouble walking, sudden falls, slurred speech, and difficulty moving the eyes up and down. […] As the disease gets worse, these kids might have trouble learning, face mental health problems, or even experience memory loss, eventually losing the ability to talk. […] In the later stages, people with Niemann-Pick disease type C might lose the ability to move their face muscles or swallow, needing a tube for feeding through the stomach. […] For those diagnosed during childhood, the disease is often fatal in the late teens or twenties because of pneumonia. […] People diagnosed in adulthood generally survive for 10 to 20 years after diagnosis.

• #144 Niemann-Pick disease type C | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-5-16

  The age of onset of the systemic symptoms is not related with that of the neurological disease (the latter can occur many years or even decades later), while there is a correlation between the age of onset of the neurological symptoms and the general further course of the disease and lifespan. […] Patients with the severe neurologic early infantile form often die between 3 and 5 years of age, those with a late-infantile neurologic onset usually between 7 and 12. Patients with a juvenile neurologic onset survive until adolescence or later, with a sizable proportion reaching the age of 30. In a review of 68 cases with adult onset, the mean age at death (on 20 patients) was 38 10.2 years, but some patients have reached the age of 70.

• #145 Understanding the phenotypic variability in Niemann-Pick disease type C (NPC): a need for precision medicine | npj Genomic Medicine

  https://www.nature.com/articles/s41525-023-00365-w

  Niemann-Pick type C (NPC) disease is a lysosomal storage disease (LSD) characterized by the buildup of endo-lysosomal cholesterol and glycosphingolipids due to loss of function mutations in the NPC1 and NPC2 genes. NPC patients can present with a broad phenotypic spectrum, with differences at the age of onset, rate of progression, severity, organs involved, effects on the central nervous system, and even response to pharmacological treatments. […] Clinical presentations of NPC disease are highly heterogeneous and vary from a rapidly progressing neonatal form to an adult-onset chronic neurodegenerative condition. The life expectancy of the patients ranges from a few days until over 60 years of age, but most patients survive to 10-25 years of age, although probably this is an underestimation.

• #146 Niemann-Pick disease type A – Metabolic Support UKAccessibility ToolsIncrease TextDecrease TextGrayscaleHigh ContrastNegative ContrastLight BackgroundLinks UnderlineReadable FontReset

  https://metabolicsupportuk.org/condition/niemann-pick-disease-type-a/

  Signs and symptoms of ASMD NP- A to look out for include: Cherry red spot in the centre of the eye […] Feeding problems […] Neurological disorders (such as loss of reflexes and reaction time) […] Swelling of the abdomen […] Yellow like skin (Jaundice) […] Unexpected growth rate […] Uncontrolled muscular movement (Athetosis) […] Swollen lymph nodes […] If your child is diagnosed with NPD, they may also develop a large liver and spleen, this is otherwise known as hepatosplenomegaly. […] This condition usually appears during infancy and sadly many infants diagnosed with ASMD NP- A do not survive past the age of 3. […] Unfortunately, there is no effective treatment for ASMD NP- A. Supportive care is recommended for this condition. […] Nieman pick type 1 is a progressive condition, so they earlier the intervention the better.

• #147 What Is Niemann-Pick Disease?

  https://www.verywellhealth.com/niemann-pick-disease-4158754

  The symptoms of Niemann-Pick type C can begin at any age but generally start in early childhood. The symptoms include learning delay, muscle weakness, and decreased coordination. These problems begin after the skills had already been developing normally for a few years. […] Children with Niemann-Pick type C may also lose the ability to look up and down with their eyes and can develop a yellowish skin color. Trouble speaking and walking may develop, along with clumsiness. Seizures and jerking muscles, as well as episodes of sudden loss of muscle tone in response to strong emotions are all the result of brain involvement. […] There is no cure for Niemann-Pick type C. Treatment is directed towards relieving the symptoms, providing pain control, and maximizing comfort.

• #148 Niemann-Pick disease – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/niemann-pick/diagnosis-treatment/drc-20355890

  Diagnosis of Niemann-Pick disease begins with a physical exam. The exam may show an early warning sign such as a liver or spleen that is too large. […] Niemann-Pick disease is rare, and its symptoms can be similar to those of other health conditions, so testing is needed to get the right diagnosis. […] No cure exists for Niemann-Pick disease, but supportive care can help manage symptoms. […] People with Niemann-Pick disease need to see their healthcare professionals regularly, because the disease and its symptoms worsen over time. […] One of the most difficult things about this condition is that it’s not possible to predict how health and development will change over time. […] You or your child will likely require more care as the condition changes.

• #149 Niemann-Pick disease treatment: a systematic review of clinical trials

  https://atm.amegroups.org/article/view/8611/html

  Miglustat is able to delay neurodegeneration, with greater benefits in patients with a late onset of the disease and -cyclodextrin-hydroxypropyl (HBP-CD) can attenuate clinical symptoms. […] In general, the most common symptoms of NPC include hepatosplenomegaly and neurologic deterioration with ataxia, motor pathologies and horizontal saccadic eye movements (HSEM). […] Until some years ago, the treatment for NP disease was based on different drugs such as anti-epileptics, anticholinergic or antidepressants to alleviate symptoms, i.e., tremor, dystonia or seizures. […] A main goal is to develop treatments in order to minimize both general symptoms and neurodegeneration. […] The trial carried out by Wraith et al. showed results from an experimental and follow-up group after 24 months of treatment in only one outcome, swallowing, and without a parallel control group receiving no treatment.

• #150 Niemann-Pick disease type C symptomatology: an expert-based clinical description | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-8-166

  While visceral manifestations tend to predominate during the perinatal and infantile period (2 months-6 years of age), neurological and psychiatric involvement is more prominent during the juvenile/adult period (6 years of age). […] Progressive cognitive decline, which always occurs in patients with NP-C, manifests as memory and executive impairment in juvenile/adult patients. […] Disease prognosis mainly correlates with the age at onset of the neurological signs, with early-onset forms progressing faster. […] Therefore, a detailed and descriptive picture of NP-C signs and symptoms may help improve disease detection and early diagnosis, so that therapy with miglustat (Zavesca), the only available treatment approved to date, can be started as soon as neurological symptoms appear, in order to slow disease progression.

• #151 Niemann-Pick disease treatment: a systematic review of clinical trials

  https://atm.amegroups.org/article/view/8611/html

  The severity score of the symptoms improved in 57% of patients. However, during the treatment epistaxis and thrombocytopenia, insomnia, leukopenia, behavioural problems, extrapyramidal symptoms, tremors, hypertransaminasemia, and especially weight loss or diarrhea, were detected in some patients. […] All of them reported the potential adverse effects of miglustat, i.e., diarrhea (present in 83.3% of patients), flatulence, weight loss and tremor (66.6%), and headache, fatigue, nasopharyngitis, dysphagia, vomiting, cough, falls and sinusitis (50%). […] Unfortunately no treatment has yet proven able to change the actual course of NPC. […] Miglustat is expected to delay the neurological symptoms of NPC, with greater benefits in patients with a late onset of the disease.

• #152 Niemann-Pick disease treatment: a systematic review of clinical trials

  https://atm.amegroups.org/article/view/8611/html

  The severity score of the symptoms improved in 57% of patients. However, during the treatment epistaxis and thrombocytopenia, insomnia, leukopenia, behavioural problems, extrapyramidal symptoms, tremors, hypertransaminasemia, and especially weight loss or diarrhea, were detected in some patients. […] All of them reported the potential adverse effects of miglustat, i.e., diarrhea (present in 83.3% of patients), flatulence, weight loss and tremor (66.6%), and headache, fatigue, nasopharyngitis, dysphagia, vomiting, cough, falls and sinusitis (50%). […] Unfortunately no treatment has yet proven able to change the actual course of NPC. […] Miglustat is expected to delay the neurological symptoms of NPC, with greater benefits in patients with a late onset of the disease.

• #153 Niemann Pick Disease – NeuImmune

  https://neuimmune.com/niemann-pick-disease/

  Niemann-Pick disease (NPD) is a rare genetic disease belonging to the lysosomal storage disorder (LSD) group. It is an inherited metabolic disorder in which abnormal amounts of lipids (fatty materials such as waxes, oils, and cholesterol) build up in the brain, spleen, liver, lungs, and bone marrow. Symptoms may include: Brain degeneration, Ataxia (lack of muscle control during voluntary movements such as walking), Loss of muscle tone, Increased sensitivity to touch, Spasticity (stiff muscles and awkward movement), Slurred speech, Swallowing and feeding difficulties. […] However, this ERT does not address the neurologic involvement in type A and A/B patients.

• #154 FDA approves two treatments for Niemann-Pick Disease – Drug Discovery World (DDW)

  https://www.ddw-online.com/fda-approves-two-treatments-for-niemann-pick-disease-31678-202409/

  Miplyffa, in combination with the enzyme inhibitor miglustat, is approved to treat neurological symptoms associated with NPC in adults and children two years of age and older. […] Aqneursa was approved for the treatment of neurological symptoms associated NPC in adults and paediatric patients weighing at least 15kg. […] NPC is a rare genetic disease that results in progressive neurological symptoms and organ dysfunction. […] On average, individuals affected by this devastating disease only live for about 13 years. […] Compared to placebo, Miplyffa resulted in a slower disease progression as measured by the R4DNPCCSS score. […] NPC is a serious disease that leads to enormous adverse impacts on patients and families.

• #155 FDA approves two treatments for Niemann-Pick Disease – Drug Discovery World (DDW)

  https://www.ddw-online.com/fda-approves-two-treatments-for-niemann-pick-disease-31678-202409/

  Miplyffa, in combination with the enzyme inhibitor miglustat, is approved to treat neurological symptoms associated with NPC in adults and children two years of age and older. […] Aqneursa was approved for the treatment of neurological symptoms associated NPC in adults and paediatric patients weighing at least 15kg. […] NPC is a rare genetic disease that results in progressive neurological symptoms and organ dysfunction. […] On average, individuals affected by this devastating disease only live for about 13 years. […] Compared to placebo, Miplyffa resulted in a slower disease progression as measured by the R4DNPCCSS score. […] NPC is a serious disease that leads to enormous adverse impacts on patients and families.

• #156 FDA approves two treatments for Niemann-Pick Disease – Drug Discovery World (DDW)

  https://www.ddw-online.com/fda-approves-two-treatments-for-niemann-pick-disease-31678-202409/

  Miplyffa, in combination with the enzyme inhibitor miglustat, is approved to treat neurological symptoms associated with NPC in adults and children two years of age and older. […] Aqneursa was approved for the treatment of neurological symptoms associated NPC in adults and paediatric patients weighing at least 15kg. […] NPC is a rare genetic disease that results in progressive neurological symptoms and organ dysfunction. […] On average, individuals affected by this devastating disease only live for about 13 years. […] Compared to placebo, Miplyffa resulted in a slower disease progression as measured by the R4DNPCCSS score. […] NPC is a serious disease that leads to enormous adverse impacts on patients and families.

• #157 Niemann-Pick Disease Type C Market Expected to Exhibit a CAGR of 17.05% During 2025-2035, Impelled by Rising Awareness and Early Diagnosis – BioSpace

  https://www.biospace.com/press-releases/niemann-pick-disease-type-c-market-expected-to-exhibit-a-cagr-of-17-05-during-2025-2035-impelled-by-rising-awareness-and-early-diagnosis

  Better patient outcomes, slower disease progression, and higher quality of life are more frequently observed. […] These advancements, specifically addressing the genetic and molecular underpinnings of NPC, result in enhanced efficacy and reduced side effects. […] Newer avenues such as gene therapy and neuroprotective agents are offering options for patients with severe or rapidly progressing disease.

• #158 Niemann-Pick Disease Type C Market Expected to Exhibit a CAGR of 17.05% During 2025-2035, Impelled by Rising Awareness and Early Diagnosis – BioSpace

  https://www.biospace.com/press-releases/niemann-pick-disease-type-c-market-expected-to-exhibit-a-cagr-of-17-05-during-2025-2035-impelled-by-rising-awareness-and-early-diagnosis

  Better patient outcomes, slower disease progression, and higher quality of life are more frequently observed. […] These advancements, specifically addressing the genetic and molecular underpinnings of NPC, result in enhanced efficacy and reduced side effects. […] Newer avenues such as gene therapy and neuroprotective agents are offering options for patients with severe or rapidly progressing disease.

• #159 Niemann-Pick Disease Type C Market Expected to Exhibit a CAGR of 17.05% During 2025-2035, Impelled by Rising Awareness and Early Diagnosis – BioSpace

  https://www.biospace.com/press-releases/niemann-pick-disease-type-c-market-expected-to-exhibit-a-cagr-of-17-05-during-2025-2035-impelled-by-rising-awareness-and-early-diagnosis

  Better patient outcomes, slower disease progression, and higher quality of life are more frequently observed. […] These advancements, specifically addressing the genetic and molecular underpinnings of NPC, result in enhanced efficacy and reduced side effects. […] Newer avenues such as gene therapy and neuroprotective agents are offering options for patients with severe or rapidly progressing disease.

• #160 Niemann-Pick Disease Type C Market Expected to Exhibit a CAGR of 17.05% During 2025-2035, Impelled by Rising Awareness and Early Diagnosis – BioSpace

  https://www.biospace.com/press-releases/niemann-pick-disease-type-c-market-expected-to-exhibit-a-cagr-of-17-05-during-2025-2035-impelled-by-rising-awareness-and-early-diagnosis

  Better patient outcomes, slower disease progression, and higher quality of life are more frequently observed. […] These advancements, specifically addressing the genetic and molecular underpinnings of NPC, result in enhanced efficacy and reduced side effects. […] Newer avenues such as gene therapy and neuroprotective agents are offering options for patients with severe or rapidly progressing disease.

• #161 Niemann-Pick Disease Type C Market Expected to Exhibit a CAGR of 17.05% During 2025-2035, Impelled by Rising Awareness and Early Diagnosis – BioSpace

  https://www.biospace.com/press-releases/niemann-pick-disease-type-c-market-expected-to-exhibit-a-cagr-of-17-05-during-2025-2035-impelled-by-rising-awareness-and-early-diagnosis

  Better patient outcomes, slower disease progression, and higher quality of life are more frequently observed. […] These advancements, specifically addressing the genetic and molecular underpinnings of NPC, result in enhanced efficacy and reduced side effects. […] Newer avenues such as gene therapy and neuroprotective agents are offering options for patients with severe or rapidly progressing disease.

• #162 Niemann-Pick Disease | Baby’s First Test | Newborn Screening | Baby Health

  https://babysfirsttest.org/newborn-screening/conditions/niemann-pick-disease

  Niemann-Pick disease type B (NPD-B) is generally associated with milder symptoms and a longer lifespan. In fact, individuals with this form of the condition usually live into adulthood, though they may have many health complications. […] Early detection and proper treatment can help improve the quality of life in babies with NPD-A and the long term outcome of babies with NPD-B. This is why newborn screening for NPD is so important.

• #163 Family Affected by Niemann-Pick Disease Type C Faces Challenges During COVID-19 – Patient Worthy

  https://patientworthy.com/2020/04/17/family-affected-niemann-pick-disease-type-c-challenges/

  Abby especially appears to have seen much less disease progression at her age when compared to Belle, which is a testament to the value of early intervention in genetic disorders like Niemann-Pick disease type C. […] The girls, especially Belle, are at heightened risk of severe infection because of the effects of Niemann-Pick on the respiratory system.

• #164 Niemann-Pick disease treatment: a systematic review of clinical trials

  https://atm.amegroups.org/article/view/8611/html

  The severity score of the symptoms improved in 57% of patients. However, during the treatment epistaxis and thrombocytopenia, insomnia, leukopenia, behavioural problems, extrapyramidal symptoms, tremors, hypertransaminasemia, and especially weight loss or diarrhea, were detected in some patients. […] All of them reported the potential adverse effects of miglustat, i.e., diarrhea (present in 83.3% of patients), flatulence, weight loss and tremor (66.6%), and headache, fatigue, nasopharyngitis, dysphagia, vomiting, cough, falls and sinusitis (50%). […] Unfortunately no treatment has yet proven able to change the actual course of NPC. […] Miglustat is expected to delay the neurological symptoms of NPC, with greater benefits in patients with a late onset of the disease.

• #165 FDA approves two treatments for Niemann-Pick Disease – Drug Discovery World (DDW)

  https://www.ddw-online.com/fda-approves-two-treatments-for-niemann-pick-disease-31678-202409/

  Miplyffa, in combination with the enzyme inhibitor miglustat, is approved to treat neurological symptoms associated with NPC in adults and children two years of age and older. […] Aqneursa was approved for the treatment of neurological symptoms associated NPC in adults and paediatric patients weighing at least 15kg. […] NPC is a rare genetic disease that results in progressive neurological symptoms and organ dysfunction. […] On average, individuals affected by this devastating disease only live for about 13 years. […] Compared to placebo, Miplyffa resulted in a slower disease progression as measured by the R4DNPCCSS score. […] NPC is a serious disease that leads to enormous adverse impacts on patients and families.

• #166 Niemann-Pick disease treatment: a systematic review of clinical trials

  https://atm.amegroups.org/article/view/8611/html

  The severity score of the symptoms improved in 57% of patients. However, during the treatment epistaxis and thrombocytopenia, insomnia, leukopenia, behavioural problems, extrapyramidal symptoms, tremors, hypertransaminasemia, and especially weight loss or diarrhea, were detected in some patients. […] All of them reported the potential adverse effects of miglustat, i.e., diarrhea (present in 83.3% of patients), flatulence, weight loss and tremor (66.6%), and headache, fatigue, nasopharyngitis, dysphagia, vomiting, cough, falls and sinusitis (50%). […] Unfortunately no treatment has yet proven able to change the actual course of NPC. […] Miglustat is expected to delay the neurological symptoms of NPC, with greater benefits in patients with a late onset of the disease.

• #167 Niemann-Pick Disease Type C Market Expected to Exhibit a CAGR of 17.05% During 2025-2035, Impelled by Rising Awareness and Early Diagnosis – BioSpace

  https://www.biospace.com/press-releases/niemann-pick-disease-type-c-market-expected-to-exhibit-a-cagr-of-17-05-during-2025-2035-impelled-by-rising-awareness-and-early-diagnosis

  Better patient outcomes, slower disease progression, and higher quality of life are more frequently observed. […] These advancements, specifically addressing the genetic and molecular underpinnings of NPC, result in enhanced efficacy and reduced side effects. […] Newer avenues such as gene therapy and neuroprotective agents are offering options for patients with severe or rapidly progressing disease.

• #168 Niemann-Pick disease – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/niemann-pick/diagnosis-treatment/drc-20355890

  Diagnosis of Niemann-Pick disease begins with a physical exam. The exam may show an early warning sign such as a liver or spleen that is too large. […] Niemann-Pick disease is rare, and its symptoms can be similar to those of other health conditions, so testing is needed to get the right diagnosis. […] No cure exists for Niemann-Pick disease, but supportive care can help manage symptoms. […] People with Niemann-Pick disease need to see their healthcare professionals regularly, because the disease and its symptoms worsen over time. […] One of the most difficult things about this condition is that it’s not possible to predict how health and development will change over time. […] You or your child will likely require more care as the condition changes.

• #169 Advancing diagnosis and treatment of Niemann-Pick C disease through biomarker discovery

  https://www.explorationpub.com/Journals/ent/Article/100412

  Diagnosis of NPC is challenging due to the rarity of the disorder, the heterogeneity of disease onset and presentation, its non-specific early symptoms, and the complexity of the laboratory testing. […] The slowly progressive nature and clinical heterogeneity in NPC are daunting with respect to development of new treatments. […] The disappointing regulatory outcomes for the recent Phase 2b/3 trials for arimoclomol and for 2-hydroxypropyl–cyclodextrin underscore the challenges in conducting an interventional clinical trial for this disorder. […] Thus, there is an urgent need for new biomarkers that could serve as surrogate endpoints to accelerate drug approval.

• #170 Advancing diagnosis and treatment of Niemann-Pick C disease through biomarker discovery

  https://www.explorationpub.com/Journals/ent/Article/100412

  Niemann-Pick C disease is a rare neurodegenerative, lysosomal storage disease caused by accumulation of unesterified cholesterol. […] The clinical presentation of NPC is highly heterogeneous and can generally be classified into four categories based on age at onset of neurological manifestations and disease progression: early-infantile, late-infantile, juvenile, and adolescent/adult-onset. […] For patients that progress to neurological signs, many early signs are non-specific (e.g., delayed developmental milestones and clumsiness), and typically advance to more specific neurological manifestations, such as cerebellar ataxia, vertical supranuclear gaze palsy, cataplexy, and dementia. […] These manifestations are progressive and patients often succumb to the disease within the first two decades of life.

• #171 Niemann-Pick disease type C symptomatology: an expert-based clinical description | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-8-166

  Niemann-Pick disease type C (NP-C) is a rare, progressive, irreversible disease leading to disabling neurological manifestations and premature death. […] NP-C is characterised by visceral, neurological and psychiatric manifestations that are not specific to the disease and that can be found in other conditions. […] Early disease detection should rely on seeking a combination of signs and symptoms, rather than isolated findings. […] Examples of combinations which are strongly suggestive of NP-C include: splenomegaly and vertical supranuclear gaze palsy (VSGP); splenomegaly and clumsiness; splenomegaly and schizophrenia-like psychosis; psychotic symptoms and cognitive decline; and ataxia with dystonia, dysarthria/dysphagia and cognitive decline. […] VSGP is a hallmark of NP-C and becomes highly specific of the disease when it occurs in combination with other manifestations (e.g. splenomegaly, ataxia).

• #172 A Rare Case of Late Adult-Onset Niemann-Pick Disease Type C

  https://www.e-jmd.org/journal/view.php?number=278

  In adult-onset NPC, diagnostic delay is common and often 5 years or more, as seen in our case. […] VSGP is present in approximately 70-80% of the patients across all age at onset categories, which suggests that clinicians should consider NPC in the differential diagnosis of VSGP, regardless of age at onset. […] The absence of VSGP cannot rule out the diagnosis of NPC, and eye movements need to be checked regularly in patients with suspected NPC, but without VSGP.

• #173

  https://omim.org/entry/257220

  Adult-onset forms, with insidious onset and slower progression, have also been reported. […] The average age of diagnosis was 10.4 years, with one-half of patients being diagnosed before the age of 6.9 years, and the average age of death was 16.2 years, with one-half of all patients dying before the age of 12.5 years. […] Common developmental difficulties included clumsiness (87%), learning difficulties (87%), ataxia (83%), dysphagia (80%), and vertical gaze palsy (81%). […] As the disease progresses, dystonia and seizures may occur. […] The characteristic ocular abnormality (supranuclear gaze palsy) usually appears early in the course of the disease but can be very subtle initially and only detected by detailed ophthalmologic assessment.

• #174 Niemann-Pick Disease Type C – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK1296/

  Adolescents or adults may present with neurologic disease as described in the preceding section, albeit with a much slower rate of progression. The author has seen one individual who survived into the seventh decade, having first developed symptoms 25 years earlier. Older individuals may also present with apparent psychiatric illness, sometimes appearing to have major depression or schizophrenia. The psychiatric manifestations may overshadow neurologic signs, although the latter can usually be detected with careful examination.

• #175 Niemann-Pick disease type C symptomatology: an expert-based clinical description | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-8-166

  While visceral manifestations tend to predominate during the perinatal and infantile period (2 months-6 years of age), neurological and psychiatric involvement is more prominent during the juvenile/adult period (6 years of age). […] Progressive cognitive decline, which always occurs in patients with NP-C, manifests as memory and executive impairment in juvenile/adult patients. […] Disease prognosis mainly correlates with the age at onset of the neurological signs, with early-onset forms progressing faster. […] Therefore, a detailed and descriptive picture of NP-C signs and symptoms may help improve disease detection and early diagnosis, so that therapy with miglustat (Zavesca), the only available treatment approved to date, can be started as soon as neurological symptoms appear, in order to slow disease progression.

• #176 A Rare Case of Late Adult-Onset Niemann-Pick Disease Type C

  https://www.e-jmd.org/journal/view.php?number=278

  Niemann-Pick disease type C (NPC) is characterized by heterogeneity in age at onset, which is related to variance in clinical presentation and progression. […] Adult-onset NPC shows a wide spectrum of neurological symptoms such as vertical supranuclear gaze palsy (VSGP), ataxia, dystonia, cognitive decline and psychosis, and less commonly visceral involvement. […] Early diagnosis of NPC is important because treatment with miglustat has been shown to stabilize disease progression. […] The patient had onset of symptoms at 57 years of age. […] His clinical symptoms suggested the possibility of NPC or progressive supranuclear palsy with predominant cerebellar ataxia (PSP-C). […] The NPC suspicion index score was 100, indicating its high probability. […] Clinical features of this patient strongly suggest NPC.

• #177 Niemann-Pick Disease | Baby’s First Test | Newborn Screening | Baby Health

  https://babysfirsttest.org/newborn-screening/conditions/niemann-pick-disease

  Niemann-Pick disease type B (NPD-B) is generally associated with milder symptoms and a longer lifespan. In fact, individuals with this form of the condition usually live into adulthood, though they may have many health complications. […] Early detection and proper treatment can help improve the quality of life in babies with NPD-A and the long term outcome of babies with NPD-B. This is why newborn screening for NPD is so important.

• #178 Niemann-Pick Disease Type C Market Expected to Exhibit a CAGR of 17.05% During 2025-2035, Impelled by Rising Awareness and Early Diagnosis – BioSpace

  https://www.biospace.com/press-releases/niemann-pick-disease-type-c-market-expected-to-exhibit-a-cagr-of-17-05-during-2025-2035-impelled-by-rising-awareness-and-early-diagnosis

  Niemann-Pick Disease Type C (NPC), represents an extremely severe and heartbreaking disorder that primarily occurs in children and adolescents worldwide. […] The resulting clinical picture is characterized by devastating neurological decline, significant motor dysfunction, and progressive cognitive impairment, often manifesting in early childhood. […] As the disease relentlessly progresses, the burden on patients and their families intensifies, creating a profound emotional and physical strain. […] This debilitating trajectory underscores the critical and urgent need for therapies that go beyond simply managing symptoms and actively modify the course of this devastating disease. […] Advanced treatments like gene therapy, substrate reduction therapy (SRT), and chaperone therapies can be tailored with this granular perspective to maximize their efficacy and reduce any potential side effects.

• #179 Niemann-Pick disease type C symptomatology: an expert-based clinical description | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-8-166

  Niemann-Pick disease type C (NP-C) is a rare, progressive, irreversible disease leading to disabling neurological manifestations and premature death. […] NP-C is characterised by visceral, neurological and psychiatric manifestations that are not specific to the disease and that can be found in other conditions. […] Early disease detection should rely on seeking a combination of signs and symptoms, rather than isolated findings. […] Examples of combinations which are strongly suggestive of NP-C include: splenomegaly and vertical supranuclear gaze palsy (VSGP); splenomegaly and clumsiness; splenomegaly and schizophrenia-like psychosis; psychotic symptoms and cognitive decline; and ataxia with dystonia, dysarthria/dysphagia and cognitive decline. […] VSGP is a hallmark of NP-C and becomes highly specific of the disease when it occurs in combination with other manifestations (e.g. splenomegaly, ataxia).

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