Materiały źródłowe

• #1 Metachromatic leukodystrophy – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/metachromatic-leukodystrophy/symptoms-causes/syc-20354733

  Metachromatic leukodystrophy is a rare hereditary (genetic) disorder that causes fatty substances (lipids) to build up in cells, particularly in the brain, spinal cord and peripheral nerves. This buildup is caused by a deficiency of an enzyme that helps break down lipids called sulfatides. The brain and nervous system progressively lose function because the substance that covers and protects the nerve cells (myelin) is damaged. […] The infantile form is the most common and progresses more rapidly than the other forms. […] Damage to the protective myelin covering the nerves results in progressive worsening of brain and nervous system functions, including: Loss of the ability to detect sensations, such as touch, pain, heat and sound; Loss of intellectual, thinking and memory skills; Loss of motor skills, such as walking, moving, speaking and swallowing; Stiff, rigid muscles, poor muscle function and paralysis; Loss of bladder and bowel function; Gallbladder problems; Blindness; Hearing loss; Seizures; Emotional and behavioral problems, including unstable emotions and substance misuse.

• #2 Metachromatic leukodystrophy: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/metachromatic-leukodystrophy/

  Metachromatic leukodystrophy is an inherited disorder characterized by the accumulation of fats called sulfatides in cells. This accumulation especially affects cells in the nervous system that produce myelin, the substance that insulates and protects nerves. Nerve cells covered by myelin make up a tissue called white matter. Sulfatide accumulation in myelin-producing cells causes progressive destruction of white matter (leukodystrophy) throughout the nervous system, including in the brain and spinal cord (the central nervous system) and the nerves connecting the brain and spinal cord to muscles and sensory cells that detect sensations such as touch, pain, heat, and sound (the peripheral nervous system). […] In people with metachromatic leukodystrophy, white matter damage causes progressive deterioration of intellectual functions and motor skills, such as the ability to walk. Affected individuals also develop loss of sensation in the extremities (peripheral neuropathy), incontinence, seizures, paralysis, an inability to speak, blindness, and hearing loss. Eventually they lose awareness of their surroundings and become unresponsive.

• #3 Metachromatic Leukodystrophy – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK560744/

  Metachromatic leukodystrophy is a rare lysosomal storage disease caused due to deficient activity of arylsulfatase A. It follows an autosomal recessive pattern of inheritance. It is a serious condition and causes death within 5-6 years in early-onset form. […] All forms of the disease involve a progressive deterioration of neurodevelopment and neurocognitive function. […] Metachromatic leukodystrophy is a progressive disease. This means that the symptoms tend to get worse over time. People who have this disease lose all muscle and mental functions eventually. Lifespan often depends on the age at which a person is first diagnosed. […] The prognosis is worse than later-onset forms of the diseases; progression to death typically occurs within five to six years. […] Progression is slower in this form of the disease, and the patients may survive until early adulthood. […] The disease course in this form of the disease may be static or of insidious progression.

• #4 Metachromatic Leukodystrophy (MLD) | Medical School

  https://med.umn.edu/pediatrics/programs-centers-institutes/leukodystrophy-center/metachromatic-leukodystrophy

  Metachromatic leukodystrophy is a rare, inherited disorder affecting approximately 1 in 40,000 children, which leads to damage of the brain and peripheral nerves. The disease is progressive and lethal. […] With the accumulation of sulfatide causing the breakdown of myelin, a patients coordination, strength, and cognition are affected. […] The first and most common is Late Infantile MLD, which typically becomes evident between 6 and 30 months of age. The child will develop normally until the onset of the disease, then start displaying changes in gross motor skills. They may become delayed in learning to walk or begin to stagger and fall frequently. Eventually, the child will lose abilities that they had, including speaking, moving, and even swallowing. […] The second type, Juvenile MLD, typically appears between 30 months and 17 years of life. It is sometimes broken down further into early juvenile (30 months to 7 years) and late juvenile MLD (ages 7 through 16). The disease first affects the ability to run and walk, and the child loses coordination. Mentally, the child may develop emotional or behavioral difficulties, have trouble following directions, and/or experience academic difficulties.

• #5 Metachromatic leukodystrophy – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/metachromatic-leukodystrophy/symptoms-causes/syc-20354733

  Each form of metachromatic leukodystrophy occurs at a different age and can have different initial signs and symptoms and rates of progression: Late infantile form. This is the most common form of metachromatic leukodystrophy, starting around 2 years of age or younger. Progressive loss of speech and muscle function occurs rapidly. Children with this form often do not survive beyond childhood. […] Juvenile form. This is the second most common form and starts in children between 3 and 16 years of age. Early signs are behavior and cognitive problems and increasing difficulty in school. Loss of the ability to walk may occur. Although the juvenile form doesn’t progress as fast as the late infantile form, survival is generally less than 20 years after symptoms begin. […] Adult form. This form is less common and typically starts after age 16. Signs progress slowly and may begin with behavior and psychiatric problems, drug and alcohol misuse, and issues with school and work. Psychotic symptoms such as delusions and hallucinations may occur. The course of this form varies, with periods of stable symptoms and periods of rapid decline in functioning. Adults may survive for several decades after initial symptoms.

• #6 Metachromatic leukodystrophy: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/metachromatic-leukodystrophy/

  The most common form of metachromatic leukodystrophy, affecting about 50 to 60 percent of all individuals with this disorder, is called the late infantile form. This form of the disorder usually appears in the second year of life. Affected children lose any speech they have developed, become weak, and develop problems with walking (gait disturbance). As the disorder worsens, muscle tone generally first decreases, and then increases to the point of rigidity. Individuals with the late infantile form of metachromatic leukodystrophy typically do not survive past childhood. […] In 20 to 30 percent of individuals with metachromatic leukodystrophy, onset occurs between the age of 4 and adolescence. In this juvenile form, the first signs of the disorder may be behavioral problems and increasing difficulty with schoolwork. Progression of the disorder is slower than in the late infantile form, and affected individuals may survive for about 20 years after diagnosis.

• #7 Understanding caregiver descriptions of initial signs and symptoms to improve diagnosis of metachromatic leukodystrophy | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-022-02518-z

  Metachromatic leukodystrophy (MLD), a relentlessly progressive and ultimately fatal condition, is a rare autosomal recessive lysosomal storage disorder caused by a deficiency of the enzyme arylsulfatase A (ARSA). MLD is characterized by progressive motor and cognitive deterioration. Typically, MLD is classified into 3 subtypes by age of onset of first symptoms, including late infantile (symptom onset30 months of age); juvenile, subdivided into early juvenile (onset30 months and7 years) and late-juvenile (onset7 years and17 years); and adult (onset17 years). Late infantile and early juvenile MLD together (onset7 years) is more broadly classified as early-onset MLD (symptoms onset7 years of age). […] The understanding of the caregiver language at symptom onset sheds light on a critical window of often missed opportunity for earlier diagnosis and therapeutic intervention in MLD.

• #8 Frontiers | Metachromatic Leukodystrophy: Diagnosis, Modeling, and Treatment Approaches

  https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2020.576221/full

  Clinical manifestation of late infantile MLD begins up to 30 months of age. This form of MLD is considered the most severe, characterized by lack of or minimal residual ARSA activity, which entails rapid neurodegeneration. The disease usually starts with either gait abnormalities or delay in early motor milestones. The initial stages can be characterized by muscle weakness, pathological movements, neuropathy, as well as development regression. […] The juvenile form develops between the ages of 3 and 16 and is characterized by a less pronounced clinical manifestation in comparison with the late infantile form. In the juvenile form, cognitive impairment and behavioral changes are often observed, followed by deterioration of central and peripheral motility and epilepsy. […] Clinical manifestation of the adult form of MLD begins in late adolescence, usually after 16 years of age. Adult MLD is the less severe form of the disease. In the adult form, psychoses, cognitive and behavioral impairment, ataxia, polyneuropathy, and epileptic seizures are found. […] The most common form is the late infantile, which is found in 50–60% of all patients. On the other hand, 20–30% of patients are diagnosed with the juvenile form and the adult form is the most rare, affecting 15–20% of patients with MLD.

• #9 Metachromatic Leukodystrophy |

  https://www.huntershope.org/family-care/leukodystrophies/metachromatic-leukodystrophy/

  Those affected by MLD typically appear healthy until onset, or when an individual experiences symptoms of the disease. Onset can vary from the first few weeks or months of life (Early Infantile Onset) into adulthood (Adult Onset). […] Late Infantile MLD is characterized by normal development the first 6-18 months. This is followed by a progressive regression that shows first in motor skills, perhaps never learning to walk or showing deterioration of balance. The regression will rapidly affect speech, overall mobility, and basic cognitive skills. Often the muscles will painfully cramp up (rigidity), and feeding requires a G-tube or J-tube directly to the digestive system. Paralysis and blindness are often reported with a prognosis of 1-2 years, although today’s care usually extends that period to 5-7 years after diagnosis.

• #10 Metachromatic leukodystrophy late infantile form | Great Ormond Street Hospital

  https://www.gosh.nhs.uk/conditions-and-treatments/conditions-we-treat/metachromatic-leukodystrophy-late-infantile-form/

  Metachromatic leukodystrophy (MLD) is a rare inherited disorder affecting mainly the 'white matter’ of the brain, causing a progressive loss of physical and, later, mental skills. […] In the late infantile form of MLD the infants development starts to slow down between the ages of six months and two years. He or she may become rather unsettled and appear physically floppy (hypotonic). Over the following months, motor skills will not progress as expected and, indeed, skills that have been learnt will be lost. […] Over the course of the next few years the child becomes totally dependent again, usually developing stiffness of the legs (spasticity) and eventually losing all understanding or real awareness of his or her surroundings. Vision will be very reduced and sometimes epileptic seizures may develop. The condition is not a painful one and the child will be unaware of what is happening in the later stages of the disease.

• #11 Metachromatic Leukodystrophy (MLD) | UPMC Children’s Hospital

  https://www.chp.edu/our-services/rare-disease-therapy/conditions-we-treat/metachromatic-leukodystrophy

  MLD symptoms may start as early as 6 months or as late as 2 years. […] Children with late-infantile MLD often lose the ability to walk and talk within a few months of the first symptoms. […] When MLD starts later in a child’s life, its progression is often slower.

• #12 Metachromatic leukodystrophy late infantile form | Great Ormond Street Hospital

  https://www.gosh.nhs.uk/conditions-and-treatments/conditions-we-treat/metachromatic-leukodystrophy-late-infantile-form/

  Metachromatic leukodystrophy (MLD) is a rare inherited disorder affecting mainly the 'white matter’ of the brain, causing a progressive loss of physical and, later, mental skills. […] In the late infantile form of MLD the infants development starts to slow down between the ages of six months and two years. He or she may become rather unsettled and appear physically floppy (hypotonic). Over the following months, motor skills will not progress as expected and, indeed, skills that have been learnt will be lost. […] Over the course of the next few years the child becomes totally dependent again, usually developing stiffness of the legs (spasticity) and eventually losing all understanding or real awareness of his or her surroundings. Vision will be very reduced and sometimes epileptic seizures may develop. The condition is not a painful one and the child will be unaware of what is happening in the later stages of the disease.

• #13 Understanding caregiver descriptions of initial signs and symptoms to improve diagnosis of metachromatic leukodystrophy | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-022-02518-z

  Early recognition of MLD is crucial to increase the chance of individuals with MLD qualifying for and benefiting from therapy. However, the initial signs and symptoms can be subtle and non-specific, and can go unrecognized for months and years. […] Based on the coding and then grouping of caregiver-reported initial signs of MLD, coordination difficulties (75.0%), clonus/tremors (28.1%), and comprehension challenges (28.1%) were the most common types of initial symptoms described by caregivers. […] More broadly, themes of developmental delays, stagnation, and regression are described by caregivers as the first indicators of concern. […] In summary, this study highlights the detailed caregiver language used to describe red flags suggestive of the early clinical picture of MLD. […] Across all MLD individuals in this studys sample, time to diagnosis took an average of 13.7 months, which meant that in many cases individuals were too far progressed to be suitable candidates for interventional therapies, leaving palliative and supportive care as their only options.

• #14 Metachromatic leukodystrophy | Myriad Foresight® Carrier Screen

  https://myriad.com/womens-health/diseases/metachromatic-leukodystrophy/

  Individuals with MLD will progressively lose intellectual and motor functions. Symptoms may include stiffness and tightness of the muscles (spasticity), seizures, personality changes, and progressive dementia. As the disease progresses, the patient loses the ability to walk, talk, see, and hear, eventually leading to paralysis and unresponsiveness. […] By the final stages of the disease, children with infantile MLD become blind and deaf and require a feeding tube. They are unresponsive to their surroundings and eventually become paralyzed. Infantile MLD is usually fatal by the age of 10. […] The disease is usually fatal 10 to 20 years after the first symptoms appear. […] In the final stages of the disease, symptoms are similar to the infantile form: blindness, deafness, unresponsiveness, and paralysis.

• #15 Metachromatic leukodystrophy late infantile form | Great Ormond Street Hospital

  https://www.gosh.nhs.uk/conditions-and-treatments/conditions-we-treat/metachromatic-leukodystrophy-late-infantile-form/

  Metachromatic leukodystrophy (MLD) is a rare inherited disorder affecting mainly the 'white matter’ of the brain, causing a progressive loss of physical and, later, mental skills. […] In the late infantile form of MLD the infants development starts to slow down between the ages of six months and two years. He or she may become rather unsettled and appear physically floppy (hypotonic). Over the following months, motor skills will not progress as expected and, indeed, skills that have been learnt will be lost. […] Over the course of the next few years the child becomes totally dependent again, usually developing stiffness of the legs (spasticity) and eventually losing all understanding or real awareness of his or her surroundings. Vision will be very reduced and sometimes epileptic seizures may develop. The condition is not a painful one and the child will be unaware of what is happening in the later stages of the disease.

• #16 SciELO Brazil – Metachromatic leukodystrophy: pediatric presentation and the challenges of early diagnosis Metachromatic leukodystrophy: pediatric presentation and the challenges of early diagnosis

  https://www.scielo.br/j/ramb/a/4Tcf3mYwRfLMdxkTzwXxT5q/

  Metachromatic leukodystrophy (MLD; OMIM 250100) is an autosomal recessive hereditary disease caused by a deficiency of the Arylsulfatase A (ARSA) enzyme and, more rarely, of Saposin B, which is responsible for the interaction with the sulfatide, allowing the ARSA to degrade it. […] There are different variants (leading to different levels of residual enzymatic activity) and variations regarding the age of onset of the first symptoms and speed of disease progression, thus, it has been classified as: infantile (late infantile, 0 to 4 years), juvenile (4 to 15 years), and adult (over 15 years). […] The infantile type (late infantile) usually manifests during the second year of life, with a gait disorder of sudden onset as well when the child begins to learn to walk. Often, an orthopaedist is sought before the neurological manifestations appear. Strabismus, dysarthria, spasticity, and intellectual deterioration appear gradually. Coarse tremors or coarse abnormal movements (athetosis) of the extremities may appear. The deep tendon reflexes of the lower limbs are reduced or absent. In addition, spasticity episodes may be triggered by any feeling of discomfort (including constipation or cholecystopathy) and may result in severe episodes of stiffness and shaking, crying, sweating, and fever of unknown origin. During the third and fourth years of life, there is a rapid progression of the disease with the onset of visual abnormalities, such as optic atrophy and progressive amblyopia.

• #17 Understanding caregiver descriptions of initial signs and symptoms to improve diagnosis of metachromatic leukodystrophy | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-022-02518-z

  Rapid disease progression is exemplified by one caregiver who shared that their healthy child began experiencing trouble walking at 15 months. From the first signs of disease onset to diagnosis (9 months) their child had lost almost all motor function and within the following month had lost all remaining motor function. 46.7% of MLD individuals (14/30) were reported by caregivers to have signs of developmental regression within 6 months or less from onset of initial symptoms, which is often months before a diagnosis is confirmed.

• #18 Metachromatic leukodystrophy late infantile form | Great Ormond Street Hospital

  https://www.gosh.nhs.uk/conditions-and-treatments/conditions-we-treat/metachromatic-leukodystrophy-late-infantile-form/

  Metachromatic leukodystrophy (MLD) is a rare inherited disorder affecting mainly the 'white matter’ of the brain, causing a progressive loss of physical and, later, mental skills. […] In the late infantile form of MLD the infants development starts to slow down between the ages of six months and two years. He or she may become rather unsettled and appear physically floppy (hypotonic). Over the following months, motor skills will not progress as expected and, indeed, skills that have been learnt will be lost. […] Over the course of the next few years the child becomes totally dependent again, usually developing stiffness of the legs (spasticity) and eventually losing all understanding or real awareness of his or her surroundings. Vision will be very reduced and sometimes epileptic seizures may develop. The condition is not a painful one and the child will be unaware of what is happening in the later stages of the disease.

• #19 About MLD Metachromatic Leukodystrophy | MLD Support Association UK

  https://www.mldsupportuk.org.uk/about-mld/

  The most common initial signs and symptoms in children who develop MLD during the first 2 years of life are, after a period of normal growth and development, abnormal or erratic movements and other changes in the way they move particularly when they are crawling or walking. […] Unfortunately, as MLD is such a rare disease and health professionals generally see less than one or two cases in their career, these children are frequently diagnosed as cerebral palsy as they initially have problems with walking and toe walking. However, with MLD there is also deterioration in other developmental skills e.g. loss of speech. Once these symptoms become noticeable they can progress rapidly over a few months but with periods of apparent stabilisation. […] Although children with Late-infantile MLD do generally learn to walk, the movement in the limbs becomes abnormal and, as the muscles become rigid, walking ability diminishes. Speech is also affected and, as many parents have noted, this is one of the unkindest symptomsnot hearing their childrens voices again. As time goes by, limbs can become painful as contractures develop. Fine motor skills are affected, for instance writing, drawing etc. Difficulties in feeding occur and weight loss becomes a significant problem.

• #20 Metachromatic leukodystrophy late infantile form | Great Ormond Street Hospital

  https://www.gosh.nhs.uk/conditions-and-treatments/conditions-we-treat/metachromatic-leukodystrophy-late-infantile-form/

  The brains control of the muscles responsible for chewing, coughing and swallowing eventually becomes affected so that assistance with a feeding tube may be needed, and chestiness will develop and may lead to infections and increasing physical weakness. […] Eventually the combination of the diseased brain and physical weakness becomes too great to sustain life, and death usually occurs between the ages of five to eight years. Parents and carers will be aware of the childs increasing frailty, and death is usually relatively peaceful and expected when the time comes.

• #21 About MLD Metachromatic Leukodystrophy | MLD Support Association UK

  https://www.mldsupportuk.org.uk/about-mld/

  Ultimately, mobility and speech is totally lost and the child becomes bedridden. This is accompanied by a progressive cognitive decline, restricting interaction and understanding and, eventually, leading to dementia. Sight is also lost and seizures become a significant problem. […] In the early stages children often suffer increasing difficulties with movement and co-ordination and walking. They can develop slurred speech and suffer incontinence. The situation may stabilise for months or even years in some cases, but the reason for this is not yet known. However, as symptoms advance, individuals develop signs of neurological involvement such as involuntary flexion or extension of the arms and legs, tremor, muscle rigidity and, eventually, they lose the ability to walk. This is followed by a decline in motor and cognitive function and, unfortunately, the final stage of the disease follows that of the Late-infantile form of MLD, but generally over a longer period of time. […] Without intervention, as the peripheral nervous system becomes involved, movements may become clumsy and they may become incontinent. Paralysis of the arms and legs develops progressively.

• #22 Metachromatic leukodystrophy late infantile form | Great Ormond Street Hospital

  https://www.gosh.nhs.uk/conditions-and-treatments/conditions-we-treat/metachromatic-leukodystrophy-late-infantile-form/

  The brains control of the muscles responsible for chewing, coughing and swallowing eventually becomes affected so that assistance with a feeding tube may be needed, and chestiness will develop and may lead to infections and increasing physical weakness. […] Eventually the combination of the diseased brain and physical weakness becomes too great to sustain life, and death usually occurs between the ages of five to eight years. Parents and carers will be aware of the childs increasing frailty, and death is usually relatively peaceful and expected when the time comes.

• #23 Metachromatic leukodystrophy | Myriad Foresight® Carrier Screen

  https://myriad.com/womens-health/diseases/metachromatic-leukodystrophy/

  All individuals with MLD will experience mental and motor deterioration, eventually reaching a state of paralysis and unresponsiveness. […] Most children with the infantile form of MLD die by the age of 10. Those with the juvenile form typically develop symptoms between the ages of 3 and 14 and can live 10 to 20 years after the onset of symptoms. The adult form of the disease is more variable, but affected adults may not develop symptoms until their forties or fifties and can live 20 to 30 years after symptoms begin. Death most commonly occurs from pneumonia or other infections.

• #24 Insights into the natural history of metachromatic leukodystrophy from interviews with caregivers | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-019-1060-2

  Metachromatic leukodystrophy (MLD) is a rare, autosomal recessive lysosomal storage disease caused by deficient activity of arylsulfatase A. Neurological involvement results in severe disability and premature death, but understanding of the natural history of the disease remains limited. […] Patients with late-infantile MLD had a mean age of 1.5 years at symptom onset and 2.6 years at diagnosis. The most common initial symptoms in this group related to problems with gross motor function (12/16 patients); 11 patients never learned to walk independently. […] For patients with juvenile MLD, the mean ages at symptom onset and diagnosis were 8.7 years and 11.6 years, respectively. Cognitive or social/behavioural problems were the most common first reported symptoms in this group (9/16 and 7/16 patients, respectively); these were generally followed by deterioration in motor function.

• #25 Insights into the natural history of metachromatic leukodystrophy from interviews with caregivers | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-019-1060-2

  Patients with juvenile MLD, as expected, exhibited initial symptoms later than those with late-infantile MLD, at a mean age of 8.7 (4.0-14.8) years. For these patients, first symptoms often related to changes in cognitive function (9/16 patients; 56.3%) or social/behavioural function (7/16 patients; 43.8%). […] The mean age (range) at diagnosis was 11.6 (3.1-21.6) years versus 2.6 (0.4-8.6) years for patients with juvenile and late-infantile MLD, respectively. […] Patients with juvenile MLD generally had a greater delay in diagnosis than those with late-infantile MLD, with a mean time from first symptom to diagnosis of 3.7 (0.2-6.8) years versus 1.2 (0.3-7.1) years. […] Patients with late-infantile MLD generally experienced a rapid decline, with a mean time (range) from first symptom to first functional loss of 1.0 (0.2-4.0) years.

• #26 Metachromatic leukodystrophy – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/metachromatic-leukodystrophy/symptoms-causes/syc-20354733

  Each form of metachromatic leukodystrophy occurs at a different age and can have different initial signs and symptoms and rates of progression: Late infantile form. This is the most common form of metachromatic leukodystrophy, starting around 2 years of age or younger. Progressive loss of speech and muscle function occurs rapidly. Children with this form often do not survive beyond childhood. […] Juvenile form. This is the second most common form and starts in children between 3 and 16 years of age. Early signs are behavior and cognitive problems and increasing difficulty in school. Loss of the ability to walk may occur. Although the juvenile form doesn’t progress as fast as the late infantile form, survival is generally less than 20 years after symptoms begin. […] Adult form. This form is less common and typically starts after age 16. Signs progress slowly and may begin with behavior and psychiatric problems, drug and alcohol misuse, and issues with school and work. Psychotic symptoms such as delusions and hallucinations may occur. The course of this form varies, with periods of stable symptoms and periods of rapid decline in functioning. Adults may survive for several decades after initial symptoms.

• #27 Insights into the natural history of metachromatic leukodystrophy from interviews with caregivers | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-019-1060-2

  Metachromatic leukodystrophy (MLD) is a rare, autosomal recessive lysosomal storage disease caused by deficient activity of arylsulfatase A. Neurological involvement results in severe disability and premature death, but understanding of the natural history of the disease remains limited. […] Patients with late-infantile MLD had a mean age of 1.5 years at symptom onset and 2.6 years at diagnosis. The most common initial symptoms in this group related to problems with gross motor function (12/16 patients); 11 patients never learned to walk independently. […] For patients with juvenile MLD, the mean ages at symptom onset and diagnosis were 8.7 years and 11.6 years, respectively. Cognitive or social/behavioural problems were the most common first reported symptoms in this group (9/16 and 7/16 patients, respectively); these were generally followed by deterioration in motor function.

• #28 Metachromatic Leukodystrophy |

  https://www.huntershope.org/family-care/leukodystrophies/metachromatic-leukodystrophy/

  Juvenile MLD is characterized by normal development with an onset between ages 4-14. Onset usually starts with either motor or cognitive symptoms, typically not both. With the motor progression, the first signs are often changes in gait (balance/walking). Cognitive progression often begins with unexplainable behavioral outbursts accompanied by lack of memory of recent events, inability to follow simple sequences and a decline in social skills. These skills will continue to decline, along with loss of continence control, over a period of 4-8 years. Speech ability will also decline during this time. The regression is slower than in the late infantile form, but the pattern is similar affecting mobility, eating, speech and cognitive skills. Eventually the muscle tone is lost, and cramping or stiffness might occur. Safety in swallowing/feeding requires a G-tube or J-tube. Paralysis and blindness are often reported with a life expectancy of 6-8 years, however, there are reports of a slower degeneration in this group with individuals maintaining mobility and basic cognitive skills 10-12 years or more after onset.

• #29 Insights into the natural history of metachromatic leukodystrophy from interviews with caregivers | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-019-1060-2

  The rate of functional decline was more rapid in patients with late-infantile MLD than those with juvenile MLD; the mean time from first symptom to first functional loss was 1 year versus 6.1 years, respectively. […] Our data highlight clear overall differences in symptom profiles and disease progression between late-infantile and juvenile MLD, but also indicate some degree of interindividual variability within each subtype. […] Patients with late-infantile MLD had a mean age (range) of 1.5 (1.0-2.4) years at symptom onset. The most common initial symptoms reported for these patients related to problems with gross motor function (12/16 patients; 75.0%). […] By the time of diagnosis, all but one patient with late-infantile MLD had experienced symptoms relating to gross motor function.

• #30 Metachromatic Leukodystrophy Clinical Presentation: History, Physical

  https://emedicine.medscape.com/article/951840-clinical

  Features of symptoms found in patients with each of the 4 forms of metachromatic leukodystrophy (MLD) are provided in the following lists. […] The infantile form includes the following: Gait disturbances, Memory deficits, Seizures (may be present), Loss of motor developmental milestones, Decreased attention span, Speech disturbances, Decline in school performance. […] The early juvenile form includes the following: Gait disturbances, Tremors, Clumsiness, Loss of previously achieved skills, Intellectual decline, Behavioral changes, Seizures (possible). […] The late juvenile and adult forms include the following: Decreased work or school performance, Behavioral changes, Memory loss, Seizures (may be present), Psychoses, Gradual loss of motor skills. […] A study by Harrington and colleagues confirmed clear overall differences in symptom profiles and overall disease progression related to late infantile and juvenile MLD; however, each subtype was characterized by some variability among individuals.

• #31 Metachromatic Leukodystrophy |

  https://www.huntershope.org/family-care/leukodystrophies/metachromatic-leukodystrophy/

  Juvenile MLD is characterized by normal development with an onset between ages 4-14. Onset usually starts with either motor or cognitive symptoms, typically not both. With the motor progression, the first signs are often changes in gait (balance/walking). Cognitive progression often begins with unexplainable behavioral outbursts accompanied by lack of memory of recent events, inability to follow simple sequences and a decline in social skills. These skills will continue to decline, along with loss of continence control, over a period of 4-8 years. Speech ability will also decline during this time. The regression is slower than in the late infantile form, but the pattern is similar affecting mobility, eating, speech and cognitive skills. Eventually the muscle tone is lost, and cramping or stiffness might occur. Safety in swallowing/feeding requires a G-tube or J-tube. Paralysis and blindness are often reported with a life expectancy of 6-8 years, however, there are reports of a slower degeneration in this group with individuals maintaining mobility and basic cognitive skills 10-12 years or more after onset.

• #32 Metachromatic Leukodystrophy (MLD) – United Leukodystrophy Foundation

  https://ulf.org/leukodystrophies/metachromatic-leukodystrophy-mld/

  Onset is generally between 4-12 years, and the symptoms generally first become apparent during the early years of schooling where a motor disturbance or fall in scholastic performance occurs. The child may have difficulty following directions, and behavioral abnormalities may occur. Symptoms may include incontinence, difficulties in walking and slurred speech. As symptoms advance, children may develop seizures, abnormal postures, tremor, and eventually lose the ability to walk. The final stages of the disease are similar to the late infantile form. […] Initial symptoms may occur as early as 14 years and as late as 50 years. The initial indications are typically a change in personality, poor job performance and emotional lability. Initial psychiatric diagnoses such as schizophrenia or depression are common. Alcohol and drug abuse may also occur. There is eventually a progressive loss of cognitive and motor functions, usually extending over 1-3 decades.

• #33 About MLD Metachromatic Leukodystrophy | MLD Support Association UK

  https://www.mldsupportuk.org.uk/about-mld/

  Ultimately, mobility and speech is totally lost and the child becomes bedridden. This is accompanied by a progressive cognitive decline, restricting interaction and understanding and, eventually, leading to dementia. Sight is also lost and seizures become a significant problem. […] In the early stages children often suffer increasing difficulties with movement and co-ordination and walking. They can develop slurred speech and suffer incontinence. The situation may stabilise for months or even years in some cases, but the reason for this is not yet known. However, as symptoms advance, individuals develop signs of neurological involvement such as involuntary flexion or extension of the arms and legs, tremor, muscle rigidity and, eventually, they lose the ability to walk. This is followed by a decline in motor and cognitive function and, unfortunately, the final stage of the disease follows that of the Late-infantile form of MLD, but generally over a longer period of time. […] Without intervention, as the peripheral nervous system becomes involved, movements may become clumsy and they may become incontinent. Paralysis of the arms and legs develops progressively.

• #34 Metachromatic Leukodystrophy |

  https://www.huntershope.org/family-care/leukodystrophies/metachromatic-leukodystrophy/

  Juvenile MLD is characterized by normal development with an onset between ages 4-14. Onset usually starts with either motor or cognitive symptoms, typically not both. With the motor progression, the first signs are often changes in gait (balance/walking). Cognitive progression often begins with unexplainable behavioral outbursts accompanied by lack of memory of recent events, inability to follow simple sequences and a decline in social skills. These skills will continue to decline, along with loss of continence control, over a period of 4-8 years. Speech ability will also decline during this time. The regression is slower than in the late infantile form, but the pattern is similar affecting mobility, eating, speech and cognitive skills. Eventually the muscle tone is lost, and cramping or stiffness might occur. Safety in swallowing/feeding requires a G-tube or J-tube. Paralysis and blindness are often reported with a life expectancy of 6-8 years, however, there are reports of a slower degeneration in this group with individuals maintaining mobility and basic cognitive skills 10-12 years or more after onset.

• #35 Metachromatic leukodystrophy – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/metachromatic-leukodystrophy/symptoms-causes/syc-20354733

  Each form of metachromatic leukodystrophy occurs at a different age and can have different initial signs and symptoms and rates of progression: Late infantile form. This is the most common form of metachromatic leukodystrophy, starting around 2 years of age or younger. Progressive loss of speech and muscle function occurs rapidly. Children with this form often do not survive beyond childhood. […] Juvenile form. This is the second most common form and starts in children between 3 and 16 years of age. Early signs are behavior and cognitive problems and increasing difficulty in school. Loss of the ability to walk may occur. Although the juvenile form doesn’t progress as fast as the late infantile form, survival is generally less than 20 years after symptoms begin. […] Adult form. This form is less common and typically starts after age 16. Signs progress slowly and may begin with behavior and psychiatric problems, drug and alcohol misuse, and issues with school and work. Psychotic symptoms such as delusions and hallucinations may occur. The course of this form varies, with periods of stable symptoms and periods of rapid decline in functioning. Adults may survive for several decades after initial symptoms.

• #36 Metachromatic leukodystrophy – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/metachromatic-leukodystrophy/symptoms-causes/syc-20354733

  Each form of metachromatic leukodystrophy occurs at a different age and can have different initial signs and symptoms and rates of progression: Late infantile form. This is the most common form of metachromatic leukodystrophy, starting around 2 years of age or younger. Progressive loss of speech and muscle function occurs rapidly. Children with this form often do not survive beyond childhood. […] Juvenile form. This is the second most common form and starts in children between 3 and 16 years of age. Early signs are behavior and cognitive problems and increasing difficulty in school. Loss of the ability to walk may occur. Although the juvenile form doesn’t progress as fast as the late infantile form, survival is generally less than 20 years after symptoms begin. […] Adult form. This form is less common and typically starts after age 16. Signs progress slowly and may begin with behavior and psychiatric problems, drug and alcohol misuse, and issues with school and work. Psychotic symptoms such as delusions and hallucinations may occur. The course of this form varies, with periods of stable symptoms and periods of rapid decline in functioning. Adults may survive for several decades after initial symptoms.

• #37 Metachromatic Leukodystrophy: Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/951840-overview

  Patients with the early juvenile form of MLD (4-6 years) tend to present with loss of motor developmental milestones; the most obvious signs are gait disturbances, ataxia, hyperreflexia followed by hyporeflexia, seizures, and decreased cognitive function. Progression is typically less rapid than in the infantile form. Gradual deterioration in school performance may be the first sign. Rarely, the presenting problem is acute cholecystitis or pancreatitis secondary to gallbladder involvement. […] The late juvenile form of MLD (age range, 6-16 years) and the adult form (16 years) progress slowly, and patients tend to present with behavioral disturbances or decreased cognitive function. A decline in school or work performance may be recognized first. Seizures may occur in any form of MLD and may be the only initial symptom. Motor dysfunction often follows. […] Patients with the late juvenile form often survive into early adulthood. Patients with the adult form of MLD may have an even slower progression than those with the late juvenile form. Rarely, patients with the adult form may present with choreiform movements, dystonia, or both.

• #38 Metachromatic Leukodystrophy |

  https://www.huntershope.org/family-care/leukodystrophies/metachromatic-leukodystrophy/

  Adult MLD is characterized by normal development through puberty with symptoms presenting at a later age, generally from the twenties through the forties. Similar to the Juvenile cognitive form, the initial signs of adult onset are often changes in cognitive abilities and personality. The affected individual may show poor school or work performance, anxiety, bewilderment, loss of alertness, disorganization, poor judgment and/or show declining memory. Often this may be covered up or compensated for by alcoholism or other similar behaviors. Cognition, speech and balance/mobility skills will regress along with a loss of continence over a period of years. There is very little published data about the prognosis of adult onset MLD. Again, the regression is slower than in the juvenile form, but the pattern is similar.

• #39 Invitae Metachromatic Leukodystrophy Panel | Test catalog | Invitae

  https://www.invitae.com/us/providers/test-catalog/test-06174

  The juvenile form represents 20%30% of cases and is frequently subdivided into early and late-juvenile forms. The early juvenile form manifests between four and six years of age with gait and postural abnormalities, behavioral and emotional problems, vision loss, seizures, and progressive spastic tetraparesis. The late-juvenile form appears from six to sixteen years of age with an insidious progression. Impaired school performance, behavioral problems, and language regression are initially evident, followed by motor difficulties progressing to spastic tetraparesis. Premature death usually occurs between 10 and 20 years of age. […] The adult form represents 15%20% of cases and generally presents after 16 years of age with two main forms, motor and psychiatric, though affected individuals may express both categories of symptoms. The motor form presents with neurologic symptoms such as weakness, incontinence, and loss of coordination progressing to spasticity. Individuals are often misdiagnosed with multiple sclerosis or other neurodegenerative diseases. The psychiatric form presents with behavioral abnormalities such as emotional instability, unusual social interactions, poor decision making, and a progressive mental deterioration. Many patients are often misdiagnosed with schizophrenia or depression. Death usually occurs six to fourteen years after symptom onset and is most commonly due to pneumonia or other infection.

• #40 Metachromatic Leukodystrophy |

  https://www.huntershope.org/family-care/leukodystrophies/metachromatic-leukodystrophy/

  Adult MLD is characterized by normal development through puberty with symptoms presenting at a later age, generally from the twenties through the forties. Similar to the Juvenile cognitive form, the initial signs of adult onset are often changes in cognitive abilities and personality. The affected individual may show poor school or work performance, anxiety, bewilderment, loss of alertness, disorganization, poor judgment and/or show declining memory. Often this may be covered up or compensated for by alcoholism or other similar behaviors. Cognition, speech and balance/mobility skills will regress along with a loss of continence over a period of years. There is very little published data about the prognosis of adult onset MLD. Again, the regression is slower than in the juvenile form, but the pattern is similar.

• #41 VUmc.com – Metachromatic leukodystrophy

  https://www.vumc.com/departments/center-for-children-with-white-matter-disorders/white-matter-disorders-classification/hereditary-white-matter-disorders-classified/metachromatic-leukodystrophy.htm

  First symptoms of patients with the late infantile form of the disease start mostly between 12 and 24 months of age and include rapidly progressive spasticity (stiffness), ataxia (balance and fine motor problems), loss of walking and sitting and problems with speech and swallowing (pseudobulbar symptoms). […] If peripheral neuropathy is prominent, hypotonia and ataxia are present from the start, later changing into spastic paresis. Painful tonic spasms are common. Loss of speech and dementia ensue as well as loss of vision. Epilepsy is frequent in the late stage. The early juvenile form resembles the late-infantile form, but with a slower decline. In the late-juvenile and the adult forms, psychiatric symptoms are much more prominent with attention problems, slow dementia and psychosis. These symptoms often have an insidious beginning, making it difficult to pinpoint the start of the disease. Motor symptoms as spasticity and ataxia are usually mild and progress at a slow pace. Peripheral neuropathy is found in almost all patients, but may be very mild.

• #42 Metachromatic leukodystrophy – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/metachromatic-leukodystrophy/symptoms-causes/syc-20354733

  Each form of metachromatic leukodystrophy occurs at a different age and can have different initial signs and symptoms and rates of progression: Late infantile form. This is the most common form of metachromatic leukodystrophy, starting around 2 years of age or younger. Progressive loss of speech and muscle function occurs rapidly. Children with this form often do not survive beyond childhood. […] Juvenile form. This is the second most common form and starts in children between 3 and 16 years of age. Early signs are behavior and cognitive problems and increasing difficulty in school. Loss of the ability to walk may occur. Although the juvenile form doesn’t progress as fast as the late infantile form, survival is generally less than 20 years after symptoms begin. […] Adult form. This form is less common and typically starts after age 16. Signs progress slowly and may begin with behavior and psychiatric problems, drug and alcohol misuse, and issues with school and work. Psychotic symptoms such as delusions and hallucinations may occur. The course of this form varies, with periods of stable symptoms and periods of rapid decline in functioning. Adults may survive for several decades after initial symptoms.

• #43

  https://omim.org/entry/250100

  In the adult form of metachromatic leukodystrophy, initial symptoms, which begin after age 16, are usually psychiatric and may lead to a diagnosis of schizophrenia. Disorders of movement and posture appear late. Differences from the late infantile form also include ability to demonstrate metachromatic material in paraffin- or celloidin-embedded sections and probably greater sulfatide excess in the gray than in the white matter in the adult form. […] The late-onset form of MLD is a heterogeneous group in which symptoms may develop at any age beyond 3 years. The age of demarcation of juvenile forms from adult forms is somewhat arbitrarily set at age 16 by some and age 21 by others. In the late-onset forms the disease progresses more slowly, and in mild cases the diagnosis may even go unsuspected during life.

• #44 Metachromatic leukodystrophy: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/metachromatic-leukodystrophy/

  The adult form of metachromatic leukodystrophy affects approximately 15 to 20 percent of individuals with the disorder. In this form, the first symptoms appear during the teenage years or later. Often behavioral problems such as alcohol use disorder, drug abuse, or difficulties at school or work are the first symptoms to appear. The affected individual may experience psychiatric symptoms such as delusions or hallucinations. People with the adult form of metachromatic leukodystrophy may survive for 20 to 30 years after diagnosis. During this time there may be some periods of relative stability and other periods of more rapid decline.

• #45 Metachromatic leukodystrophy – Wikipedia

  https://en.wikipedia.org/wiki/Metachromatic_leukodystrophy

  Like many other genetic disorders that affect lipid metabolism, there are several forms of MLD, which are late infantile, juvenile, and adult. […] In the late infantile form, which is the most common form of MLD (5060%), affected children begin having difficulty walking after the first year of life, usually at 1524 months. Symptoms include muscle wasting and weakness, muscle rigidity, developmental delays, progressive loss of vision leading to blindness, convulsions, impaired swallowing, paralysis, and dementia. Children may become comatose. Untreated, most children with this form of MLD die by age 5, often much sooner. […] Children with the juvenile form of MLD (onset between 3 and 10 years of age) usually begin with impaired school performance, mental deterioration, and dementia, then develop symptoms similar to the late infantile form but with slower progression. Age of death is variable, but normally within 10 to 15 years of symptom onset. Some patients can live for several decades after onset. A recent trend is to try to distinguish early-juvenile (ages 37) and late-juvenile forms of the disease. Generally, early-juveniles have motor skill declines as their first symptoms while late-juveniles show cognitive declines first. […] The adult form commonly begins after age 16 often with an onset in the 4th or 5th decade of life and presents as a psychiatric disorder or progressive dementia. Adult-onset MLD usually progresses more slowly than the late infantile and juvenile forms, with a protracted course of a decade or more.

• #46 Metachromatic leukodystrophy – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/metachromatic-leukodystrophy/symptoms-causes/syc-20354733

  Metachromatic leukodystrophy is a rare hereditary (genetic) disorder that causes fatty substances (lipids) to build up in cells, particularly in the brain, spinal cord and peripheral nerves. This buildup is caused by a deficiency of an enzyme that helps break down lipids called sulfatides. The brain and nervous system progressively lose function because the substance that covers and protects the nerve cells (myelin) is damaged. […] The infantile form is the most common and progresses more rapidly than the other forms. […] Damage to the protective myelin covering the nerves results in progressive worsening of brain and nervous system functions, including: Loss of the ability to detect sensations, such as touch, pain, heat and sound; Loss of intellectual, thinking and memory skills; Loss of motor skills, such as walking, moving, speaking and swallowing; Stiff, rigid muscles, poor muscle function and paralysis; Loss of bladder and bowel function; Gallbladder problems; Blindness; Hearing loss; Seizures; Emotional and behavioral problems, including unstable emotions and substance misuse.

• #47 Metachromatic Leukodystrophy: What It Is, Causes & Symptoms

  https://my.clevelandclinic.org/health/diseases/6067-metachromatic-leukodystrophy

  Metachromatic leukodystrophy (MLD) is a genetic condition that causes a progressive decline in your mental and motor (movement) functions. Symptoms get worse over time. This damage causes a decline in mental and motor (muscle movement) functions. Symptoms of MLD get worse over time, and usually results in death years after diagnosis. […] Symptoms of metachromatic leukodystrophy can vary based on the form. In general, all forms lead to a worsening of neurological functions, including muscle movement, intellect, mood, personality and more. […] The prognosis (outlook) for metachromatic leukodystrophy is poor. Its a progressive disease, which means the symptoms spread and/or get worse over time. People with MLD eventually lose all muscle and mental functions, which results in death.

• #48 Metachromatic leukodystrophy: MedlinePlus Medical EncyclopediaLock

  https://medlineplus.gov/ency/article/001205.htm

  Metachromatic leukodystrophy (MLD) is a genetic disorder that affects nerves, muscles, other organs, and behavior. It slowly gets worse over time. […] Symptoms of MLD may include any of the following: Abnormally high or decreased muscle tone, or abnormal muscle movements, any of which may cause problems walking or frequent falls. Behavior problems, personality changes, irritability. Decreased mental function. Difficulty swallowing. Inability to perform normal tasks. Incontinence. Poor school performance. Seizures. Speech difficulties, slurring. […] MLD is a severe disease that gets worse over time. Eventually, people lose all muscle and mental function. Life span varies, depending on what age the condition started, but the disease course usually runs 3 to 20 years or more. People with this disorder are expected to have a shorter than normal lifespan. The earlier the age at diagnosis, the more quickly the disease progresses.

• #49 Metachromatic Leukodystrophy Clinical Presentation: History, Physical

  https://emedicine.medscape.com/article/951840-clinical

  Neurodevelopmental tests demonstrate the following findings in patients with infantile or early juvenile metachromatic leukodystrophy (MLD): Loss of previously achieved developmental milestones, Tremors, Truncal ataxia, Hyperreflexia progressing to hyporeflexia, Hypotonia, Gait abnormalities, Optic atrophy. […] Neurocognitive tests demonstrate the following abnormalities in patients with late juvenile or adult MLD: Dementia, Memory loss, Disinhibition, Impulsiveness, Decreased motor function, Optic atrophy.

• #50

  https://omim.org/entry/250100

  Late Infantile and Juvenile Forms: This condition was described by Greenfield (1933). In the late infantile form, onset is usually in the second year of life and death occurs before 5 years in most. Clinical features are motor symptoms, rigidity, mental deterioration, and sometimes convulsions. Early development is normal but onset occurs before 30 months of age. The cerebrospinal fluid contains elevated protein. Galactosphingosulfatides that are strongly metachromatic, doubly refractile in polarized light, and pink with PAS are found in excess in the white matter of the central nervous system, in the kidney, and in the urinary sediment (Austin, 1960). […] In a combined literature search and retrospective cohort study of patients with MLD, Mutua et al. (2025) found a high prevalence of gallbladder disease. Regardless of age of onset of MLD symptoms, most patients had gallbladder findings identified after neurologic symptoms, and the time from disease onset to severe gallbladder pathology was the same regardless of MLD subtype. Gallbladder findings at the first evaluation included polyps, sludge, or wall thickening.

• #51

  https://mpssociety.org.uk/conditions/related-conditions/metachromatic-leukodystrophy

  Metachromatic leukodystrophy (MLD) is an inherited lysosomal storage disease that progressively destroys nerve cells (neurons) in the brain and spinal cord. […] People with MLD can experience some or many symptoms from a wide spectrum which range from severe to very mild. The severity of MLD varies widely across 3 forms which are defined by the age of the patient when the first signs and symptoms start to appear. […] Symptoms experienced in MLD vary between people, these include: Developmental delay with significant reduction in physical, cognitive, behavioural, emotional, or social development, in comparison with normal expectations. Muscle contractions (hypertonia) which can interfere with movement, speech, and walking and loss of ability to coordinate muscular movement (ataxia). Uncontrolled movement of the eyes (nystagmus) and often reduced vision. Some people can have a squint in which one or both eyes turns inwards (esotropia). Epilepsy, there are different forms of epilepsy e.g. absence episodes where the person may appear to be staring into space with or without jerking or twitching movements of the eye muscles, or more generalised tonic-clonic seizures, a type of generalised seizure that affects the entire brain. Tonic-clonic seizures are more commonly associated with epilepsy.

• #52 Metachromatic Leukodystrophy – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK560744/

  Metachromatic leukodystrophy is a rare lysosomal storage disease caused due to deficient activity of arylsulfatase A. It follows an autosomal recessive pattern of inheritance. It is a serious condition and causes death within 5-6 years in early-onset form. […] All forms of the disease involve a progressive deterioration of neurodevelopment and neurocognitive function. […] Metachromatic leukodystrophy is a progressive disease. This means that the symptoms tend to get worse over time. People who have this disease lose all muscle and mental functions eventually. Lifespan often depends on the age at which a person is first diagnosed. […] The prognosis is worse than later-onset forms of the diseases; progression to death typically occurs within five to six years. […] Progression is slower in this form of the disease, and the patients may survive until early adulthood. […] The disease course in this form of the disease may be static or of insidious progression.

• #53 Patient education – Metachromatic leukodystrophy – UF Health

  https://ufhealth.org/conditions-and-treatments/metachromatic-leukodystrophy/patient-education

  Metachromatic leukodystrophy (MLD) is a genetic disorder that affects nerves, muscles, other organs, and behavior. It slowly gets worse over time. […] Symptoms of MLD may include any of the following: Abnormally high or decreased muscle tone, or abnormal muscle movements, any of which may cause problems walking or frequent falls. […] MLD is a severe disease that gets worse over time. Eventually, people lose all muscle and mental function. Life span varies, depending on what age the condition started, but the disease course usually runs 3 to 20 years or more. […] People with this disorder are expected to have a shorter than normal lifespan. The earlier the age at diagnosis, the more quickly the disease progresses.

• #54 Association of Age at Onset and First Symptoms With Disease Progression in Patients With Metachromatic Leukodystrophy – PubMed

  https://pubmed.ncbi.nlm.nih.gov/33046606/

  Objective: To compare disease progression between different onset forms of metachromatic leukodystrophy (MLD) and to investigate the influence of the type of first symptoms on the natural course and dynamic of disease progression. […] Results: Ninety-seven patients with MLD were enrolled. Patients with LI (n = 35) and EJ (n = 18) MLD exhibited similarly rapid disease progression, all starting with motor symptoms (with or without additional cognitive symptoms). In LJ (n = 38) and adult-onset (n = 6) patients, the course of the disease was as rapid as in the early-onset forms, when motor symptoms were present at disease onset, while patients with only cognitive symptoms at disease onset exhibited significantly milder disease progression, independently of their age at onset. […] Conclusions: In addition to age at onset, the type of first symptoms predicts the rate of disease progression in MLD. These findings are important for counseling and therapy. […] This study provides Class II evidence that in patients with MLD, age at onset and the type of first symptoms predict the rate of disease progression.

• #55 VUmc.com – Metachromatic leukodystrophy

  https://www.vumc.com/departments/center-for-children-with-white-matter-disorders/white-matter-disorders-classification/hereditary-white-matter-disorders-classified/metachromatic-leukodystrophy.htm

  There is a correlation between residual enzyme activity and clinical phenotype. In general, a higher residual enzyme activity is associated with a later onset and slower disease course. There is also variation in disease severity that can be observed within families that cannot be explained by enzyme activity of gene mutations in a straightforward fashion.

• #56 2 The condition | Atidarsagene autotemcel for treating metachromatic leukodystrophy | Guidance | NICE

  https://www.nice.org.uk/guidance/hst18/chapter/2-The-condition

  Metachromatic leukodystrophy (MLD) is an autosomal recessive genetic disorder, caused by a deficiency in the enzyme arylsulphatase A (ARSA). This deficiency causes sulphatides to accumulate, producing microglial damage, progressive demyelination and neurodegeneration, leading to neurological problems. MLD is a progressive and chronically disabling condition, which substantially reduces quality of life and life expectancy. MLD can broadly be divided into a presymptomatic stage with normal motor and cognitive development, followed by a developmental plateau and early onset of first symptoms. […] The late infantile (LI) type is characterised by 2 null alleles (0/0 genotype). It is the most common (40% to 60% of children affected) and most aggressive form and usually starts before 30 months. Symptoms include peripheral neuropathy, muscle weakness, sight and hearing loss, difficulty walking, loss of speech, cognitive decline, and seizures. The condition progresses rapidly so that children lose awareness of their surroundings over a few years. Death normally occurs within 5 to 8 years.

• #57 Understanding caregiver descriptions of initial signs and symptoms to improve diagnosis of metachromatic leukodystrophy | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-022-02518-z

  Early recognition of MLD is crucial to increase the chance of individuals with MLD qualifying for and benefiting from therapy. However, the initial signs and symptoms can be subtle and non-specific, and can go unrecognized for months and years. […] Based on the coding and then grouping of caregiver-reported initial signs of MLD, coordination difficulties (75.0%), clonus/tremors (28.1%), and comprehension challenges (28.1%) were the most common types of initial symptoms described by caregivers. […] More broadly, themes of developmental delays, stagnation, and regression are described by caregivers as the first indicators of concern. […] In summary, this study highlights the detailed caregiver language used to describe red flags suggestive of the early clinical picture of MLD. […] Across all MLD individuals in this studys sample, time to diagnosis took an average of 13.7 months, which meant that in many cases individuals were too far progressed to be suitable candidates for interventional therapies, leaving palliative and supportive care as their only options.

• #58 Understanding caregiver descriptions of initial signs and symptoms to improve diagnosis of metachromatic leukodystrophy | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-022-02518-z

  Rapid disease progression is exemplified by one caregiver who shared that their healthy child began experiencing trouble walking at 15 months. From the first signs of disease onset to diagnosis (9 months) their child had lost almost all motor function and within the following month had lost all remaining motor function. 46.7% of MLD individuals (14/30) were reported by caregivers to have signs of developmental regression within 6 months or less from onset of initial symptoms, which is often months before a diagnosis is confirmed.

• #59

  https://mpssociety.org.uk/conditions/related-conditions/metachromatic-leukodystrophy

  Metachromatic leukodystrophy (MLD) is an inherited lysosomal storage disease that progressively destroys nerve cells (neurons) in the brain and spinal cord. […] People with MLD can experience some or many symptoms from a wide spectrum which range from severe to very mild. The severity of MLD varies widely across 3 forms which are defined by the age of the patient when the first signs and symptoms start to appear. […] Symptoms experienced in MLD vary between people, these include: Developmental delay with significant reduction in physical, cognitive, behavioural, emotional, or social development, in comparison with normal expectations. Muscle contractions (hypertonia) which can interfere with movement, speech, and walking and loss of ability to coordinate muscular movement (ataxia). Uncontrolled movement of the eyes (nystagmus) and often reduced vision. Some people can have a squint in which one or both eyes turns inwards (esotropia). Epilepsy, there are different forms of epilepsy e.g. absence episodes where the person may appear to be staring into space with or without jerking or twitching movements of the eye muscles, or more generalised tonic-clonic seizures, a type of generalised seizure that affects the entire brain. Tonic-clonic seizures are more commonly associated with epilepsy.

• #60 MED.00148 Gene Therapy for Metachromatic Leukodystrophy

  https://provider.healthybluenc.com/dam/medpolicies/healthybluenc/active/policies/mp_pw_e003052.html

  Symptoms of MLD typically appear in early childhood, though there are different forms of the disease with varying ages of onset. Symptoms may include motor dysfunction, loss of cognitive ability, seizures, behavioral changes, and loss of vision and hearing. As the disease advances, affected individuals experience a gradual decline in their overall functioning, leading to severe disability. Peripheral neuropathy occurs with all forms of MLD and can be a presenting symptom, especially for individuals with the late-infantile form of MLD. […] MLD generally leads to premature death, typically within a few years to a couple of decades from symptom onset. Regardless of the form of the disease, the last stage is characterized by blindness, unresponsiveness, and an inability to move or speak. Individuals with the infantile form of MLD typically die by age 5 and those with juvenile MLD have progressive disease leading to death 10 to 20 years after onset. Individuals with the adult form of the disease typically live 6 to 14 years past the onset of symptoms. […] The condition is progressive in nature and leads to severe neurological impairment.

• #61 Metachromatic Leukodystrophy (MLD) – United Leukodystrophy Foundation

  https://ulf.org/leukodystrophies/metachromatic-leukodystrophy-mld/

  There are three forms of MLD, defined by the age of onset of the disease. The late infantile form of MLD is the most common, and produces symptoms between the ages of 1 and 2. The juvenile form generally becomes apparent between the ages of 4 and 12, and the adult form occurs after age 14. As with all the leukodystrophies, the symptoms can vary widely, although in all cases there is a progressive loss of physical and intellectual function over a relatively extended period of time. In general, the earlier the onset, the more rapid the progression of the disease. […] After a period of apparently normal growth and development, skills such as walking and speech may begin to deteriorate. Once clinical symptoms become noticeable, they often appear to progress rapidly over a period of several months, with alternating periods of stabilization and decline. The child eventually becomes bedridden, unable to speak or feed independently. There may be seizures at this stage, which eventually disappear. Contractures are common and apparently painful. The child is still able to smile and respond to parents at this stage, but eventually may become blind and largely unresponsive. Swallowing eventually becomes difficult and a feeding tube becomes necessary. With modern treatment and care, the child may survive for 5-10 years. Death generally occurs as the result of an infection such as pneumonia, as opposed to being a direct result of the MLD.

• #62 Metachromatic leukodystrophy | Myriad Foresight® Carrier Screen

  https://myriad.com/womens-health/diseases/metachromatic-leukodystrophy/

  All individuals with MLD will experience mental and motor deterioration, eventually reaching a state of paralysis and unresponsiveness. […] Most children with the infantile form of MLD die by the age of 10. Those with the juvenile form typically develop symptoms between the ages of 3 and 14 and can live 10 to 20 years after the onset of symptoms. The adult form of the disease is more variable, but affected adults may not develop symptoms until their forties or fifties and can live 20 to 30 years after symptoms begin. Death most commonly occurs from pneumonia or other infections.

• #63 Understanding caregiver descriptions of initial signs and symptoms to improve diagnosis of metachromatic leukodystrophy | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-022-02518-z

  Early recognition of MLD is crucial to increase the chance of individuals with MLD qualifying for and benefiting from therapy. However, the initial signs and symptoms can be subtle and non-specific, and can go unrecognized for months and years. […] Based on the coding and then grouping of caregiver-reported initial signs of MLD, coordination difficulties (75.0%), clonus/tremors (28.1%), and comprehension challenges (28.1%) were the most common types of initial symptoms described by caregivers. […] More broadly, themes of developmental delays, stagnation, and regression are described by caregivers as the first indicators of concern. […] In summary, this study highlights the detailed caregiver language used to describe red flags suggestive of the early clinical picture of MLD. […] Across all MLD individuals in this studys sample, time to diagnosis took an average of 13.7 months, which meant that in many cases individuals were too far progressed to be suitable candidates for interventional therapies, leaving palliative and supportive care as their only options.

• #64 SciELO Brazil – Metachromatic leukodystrophy: pediatric presentation and the challenges of early diagnosis Metachromatic leukodystrophy: pediatric presentation and the challenges of early diagnosis

  https://www.scielo.br/j/ramb/a/4Tcf3mYwRfLMdxkTzwXxT5q/

  Even though there is still no curative treatment for this disease, new therapeutic possibilities are emerging, such as intrathecal enzyme replacement and hematopoietic stem-cell transplantation (HSCT) associated with gene therapy. […] In short, Metachromatic Leukodystrophy is a rare, devastating, and progressive hereditary disease. Given the possibility of emerging treatments specific to this illness, it is vital to obtain an early diagnosis.

• #65 Understanding caregiver descriptions of initial signs and symptoms to improve diagnosis of metachromatic leukodystrophy | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-022-02518-z

  Early recognition of MLD is crucial to increase the chance of individuals with MLD qualifying for and benefiting from therapy. However, the initial signs and symptoms can be subtle and non-specific, and can go unrecognized for months and years. […] Based on the coding and then grouping of caregiver-reported initial signs of MLD, coordination difficulties (75.0%), clonus/tremors (28.1%), and comprehension challenges (28.1%) were the most common types of initial symptoms described by caregivers. […] More broadly, themes of developmental delays, stagnation, and regression are described by caregivers as the first indicators of concern. […] In summary, this study highlights the detailed caregiver language used to describe red flags suggestive of the early clinical picture of MLD. […] Across all MLD individuals in this studys sample, time to diagnosis took an average of 13.7 months, which meant that in many cases individuals were too far progressed to be suitable candidates for interventional therapies, leaving palliative and supportive care as their only options.

• #66 Insights into the natural history of metachromatic leukodystrophy from interviews with caregivers | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-019-1060-2

  Patients with juvenile MLD, as expected, exhibited initial symptoms later than those with late-infantile MLD, at a mean age of 8.7 (4.0-14.8) years. For these patients, first symptoms often related to changes in cognitive function (9/16 patients; 56.3%) or social/behavioural function (7/16 patients; 43.8%). […] The mean age (range) at diagnosis was 11.6 (3.1-21.6) years versus 2.6 (0.4-8.6) years for patients with juvenile and late-infantile MLD, respectively. […] Patients with juvenile MLD generally had a greater delay in diagnosis than those with late-infantile MLD, with a mean time from first symptom to diagnosis of 3.7 (0.2-6.8) years versus 1.2 (0.3-7.1) years. […] Patients with late-infantile MLD generally experienced a rapid decline, with a mean time (range) from first symptom to first functional loss of 1.0 (0.2-4.0) years.

• #67 About MLD Metachromatic Leukodystrophy | MLD Support Association UK

  https://www.mldsupportuk.org.uk/about-mld/

  The most common initial signs and symptoms in children who develop MLD during the first 2 years of life are, after a period of normal growth and development, abnormal or erratic movements and other changes in the way they move particularly when they are crawling or walking. […] Unfortunately, as MLD is such a rare disease and health professionals generally see less than one or two cases in their career, these children are frequently diagnosed as cerebral palsy as they initially have problems with walking and toe walking. However, with MLD there is also deterioration in other developmental skills e.g. loss of speech. Once these symptoms become noticeable they can progress rapidly over a few months but with periods of apparent stabilisation. […] Although children with Late-infantile MLD do generally learn to walk, the movement in the limbs becomes abnormal and, as the muscles become rigid, walking ability diminishes. Speech is also affected and, as many parents have noted, this is one of the unkindest symptomsnot hearing their childrens voices again. As time goes by, limbs can become painful as contractures develop. Fine motor skills are affected, for instance writing, drawing etc. Difficulties in feeding occur and weight loss becomes a significant problem.

• #68 Invitae Metachromatic Leukodystrophy Panel | Test catalog | Invitae

  https://www.invitae.com/us/providers/test-catalog/test-06174

  The juvenile form represents 20%30% of cases and is frequently subdivided into early and late-juvenile forms. The early juvenile form manifests between four and six years of age with gait and postural abnormalities, behavioral and emotional problems, vision loss, seizures, and progressive spastic tetraparesis. The late-juvenile form appears from six to sixteen years of age with an insidious progression. Impaired school performance, behavioral problems, and language regression are initially evident, followed by motor difficulties progressing to spastic tetraparesis. Premature death usually occurs between 10 and 20 years of age. […] The adult form represents 15%20% of cases and generally presents after 16 years of age with two main forms, motor and psychiatric, though affected individuals may express both categories of symptoms. The motor form presents with neurologic symptoms such as weakness, incontinence, and loss of coordination progressing to spasticity. Individuals are often misdiagnosed with multiple sclerosis or other neurodegenerative diseases. The psychiatric form presents with behavioral abnormalities such as emotional instability, unusual social interactions, poor decision making, and a progressive mental deterioration. Many patients are often misdiagnosed with schizophrenia or depression. Death usually occurs six to fourteen years after symptom onset and is most commonly due to pneumonia or other infection.

• #69

  https://omim.org/entry/250100

  In the adult form of metachromatic leukodystrophy, initial symptoms, which begin after age 16, are usually psychiatric and may lead to a diagnosis of schizophrenia. Disorders of movement and posture appear late. Differences from the late infantile form also include ability to demonstrate metachromatic material in paraffin- or celloidin-embedded sections and probably greater sulfatide excess in the gray than in the white matter in the adult form. […] The late-onset form of MLD is a heterogeneous group in which symptoms may develop at any age beyond 3 years. The age of demarcation of juvenile forms from adult forms is somewhat arbitrarily set at age 16 by some and age 21 by others. In the late-onset forms the disease progresses more slowly, and in mild cases the diagnosis may even go unsuspected during life.

• #70 Metachromatic leukodystrophy – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/metachromatic-leukodystrophy/diagnosis-treatment/drc-20354734

  Your doctor will perform a physical examination including a neurological exam and review symptoms and medical history to check for signs of metachromatic leukodystrophy. […] Psychological and behavioral problems may be the first signs in juvenile and adult forms of metachromatic leukodystrophy. […] Metachromatic leukodystrophy can’t be cured yet, but clinical trials hold some promise for future treatment. Current treatment is aimed at preventing nerve damage, slowing progression of the disorder, preventing complications and providing supportive care. Early recognition and intervention may improve outcomes for some people with the disorder. […] As the disorder progresses, the level of care required to meet daily needs increases. […] The level of daily physical care increases as the disease progresses.

• #71 Metachromatic Leukodystrophy – Pediatrics – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/pediatrics/inherited-disorders-of-metabolism/metachromatic-leukodystrophy

  The juvenile form manifests between 4 years and 16 years of age with gait disturbance, intellectual impairment, and findings of peripheral neuropathy. Contrary to the infantile form, deep tendon reflexes are usually brisk. […] There is currently no effective treatment for metachromatic leukodystrophy in patients with advanced symptoms. Bone marrow or stem cell transplantation may stabilize neurocognitive function in mildly symptomatic forms of the disease.

• #72 FDA Approves First Gene Therapy for Children with Metachromatic Leukodystrophy | FDA

  https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-children-metachromatic-leukodystrophy

  Metachromatic leukodystrophy is a debilitating, rare genetic disease affecting the brain and nervous system. […] This buildup causes damage to the central and peripheral nervous system, manifesting with loss of motor and cognitive function and early death. […] In children with MLD, treatment with Lenmeldy significantly reduced the risk of severe motor impairment or death compared with untreated children. […] At 5 years of age, 71% of treated children were able to walk without assistance. […] In addition, children with pre-symptomatic early juvenile and early symptomatic early juvenile MLD showed slowing of motor and/or cognitive disease. […] The most common side effects of Lenmeldy are fever and low white blood cell count, mouth sores, respiratory infections, rash, medical line infections, viral infections, fever, gastrointestinal infections and enlarged liver. […] Treatment with Lenmeldy may be associated with formation of blood clots or a type of swelling of brain tissues known as encephalitis.

• #73 New gene therapy to treat rare genetic disorder metachromatic leukodystrophy | European Medicines Agency (EMA)

  https://www.ema.europa.eu/en/news/new-gene-therapy-treat-rare-genetic-disorder-metachromatic-leukodystrophy

  Around half of patients with the faulty ARSA gene show first symptoms before and up to the age of three. […] When symptoms appear in toddlers, the course of the disease is typically severe; most children lose the ability to walk or talk within months of the first symptoms and over 75% will die within five years. […] The disease can also appear later during childhood or during adulthood. These patients also experience a decline in motor and cognitive function and ultimately die of the disease, albeit at a slower rate than the early-onset forms of the disease. […] However, in patients with the early juvenile form of MLD, who already showed symptoms when they were first given Libmeldy, the effects were less pronounced. A possible slower decline in motor function was seen while cognitive function was maintained compared to what is known about the disease progression in untreated patients. The further the disease had already progressed in these patients, the fewer positive effects could be seen. Therefore, in patients with early juvenile form of MLD who have already developed symptoms, the CAT concluded that treatment success is maximized if at the time of diagnosis, screening for treatment and treatment, children can still walk independently and have no signs of cognitive decline.

• #74 FDA Approves First Gene Therapy for Children with Metachromatic Leukodystrophy | FDA

  https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-children-metachromatic-leukodystrophy

  Metachromatic leukodystrophy is a debilitating, rare genetic disease affecting the brain and nervous system. […] This buildup causes damage to the central and peripheral nervous system, manifesting with loss of motor and cognitive function and early death. […] In children with MLD, treatment with Lenmeldy significantly reduced the risk of severe motor impairment or death compared with untreated children. […] At 5 years of age, 71% of treated children were able to walk without assistance. […] In addition, children with pre-symptomatic early juvenile and early symptomatic early juvenile MLD showed slowing of motor and/or cognitive disease. […] The most common side effects of Lenmeldy are fever and low white blood cell count, mouth sores, respiratory infections, rash, medical line infections, viral infections, fever, gastrointestinal infections and enlarged liver. […] Treatment with Lenmeldy may be associated with formation of blood clots or a type of swelling of brain tissues known as encephalitis.

• #75 MLD and your child

  https://lenmeldy.com/mld-and-your-child/

  The most common early signs of late infantile and juvenile MLD reported by caregivers are motor symptoms and cognitive symptoms. This may appear as an increasing difficulty with moving, talking, swallowing, or eating. The age when children start showing symptoms may vary depending on the form of MLD and the parts of the brain that are affected. […] Over half of children affected by MLD show symptoms before their third birthday. […] Early detection of MLD is the key to better outcomes for your child. […] This may allow you to produce sufficient ARSA enzyme to stop or slow the progression of MLD symptoms.

• #76 SciELO Brazil – Metachromatic leukodystrophy: pediatric presentation and the challenges of early diagnosis Metachromatic leukodystrophy: pediatric presentation and the challenges of early diagnosis

  https://www.scielo.br/j/ramb/a/4Tcf3mYwRfLMdxkTzwXxT5q/

  Even though there is still no curative treatment for this disease, new therapeutic possibilities are emerging, such as intrathecal enzyme replacement and hematopoietic stem-cell transplantation (HSCT) associated with gene therapy. […] In short, Metachromatic Leukodystrophy is a rare, devastating, and progressive hereditary disease. Given the possibility of emerging treatments specific to this illness, it is vital to obtain an early diagnosis.

• #77 New gene therapy to treat rare genetic disorder metachromatic leukodystrophy | European Medicines Agency (EMA)

  https://www.ema.europa.eu/en/news/new-gene-therapy-treat-rare-genetic-disorder-metachromatic-leukodystrophy

  Around half of patients with the faulty ARSA gene show first symptoms before and up to the age of three. […] When symptoms appear in toddlers, the course of the disease is typically severe; most children lose the ability to walk or talk within months of the first symptoms and over 75% will die within five years. […] The disease can also appear later during childhood or during adulthood. These patients also experience a decline in motor and cognitive function and ultimately die of the disease, albeit at a slower rate than the early-onset forms of the disease. […] However, in patients with the early juvenile form of MLD, who already showed symptoms when they were first given Libmeldy, the effects were less pronounced. A possible slower decline in motor function was seen while cognitive function was maintained compared to what is known about the disease progression in untreated patients. The further the disease had already progressed in these patients, the fewer positive effects could be seen. Therefore, in patients with early juvenile form of MLD who have already developed symptoms, the CAT concluded that treatment success is maximized if at the time of diagnosis, screening for treatment and treatment, children can still walk independently and have no signs of cognitive decline.

• #78 Understanding caregiver descriptions of initial signs and symptoms to improve diagnosis of metachromatic leukodystrophy | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-022-02518-z

  Early recognition of MLD is crucial to increase the chance of individuals with MLD qualifying for and benefiting from therapy. However, the initial signs and symptoms can be subtle and non-specific, and can go unrecognized for months and years. […] Based on the coding and then grouping of caregiver-reported initial signs of MLD, coordination difficulties (75.0%), clonus/tremors (28.1%), and comprehension challenges (28.1%) were the most common types of initial symptoms described by caregivers. […] More broadly, themes of developmental delays, stagnation, and regression are described by caregivers as the first indicators of concern. […] In summary, this study highlights the detailed caregiver language used to describe red flags suggestive of the early clinical picture of MLD. […] Across all MLD individuals in this studys sample, time to diagnosis took an average of 13.7 months, which meant that in many cases individuals were too far progressed to be suitable candidates for interventional therapies, leaving palliative and supportive care as their only options.

• #79 SciELO Brazil – Metachromatic leukodystrophy: pediatric presentation and the challenges of early diagnosis Metachromatic leukodystrophy: pediatric presentation and the challenges of early diagnosis

  https://www.scielo.br/j/ramb/a/4Tcf3mYwRfLMdxkTzwXxT5q/

  Even though there is still no curative treatment for this disease, new therapeutic possibilities are emerging, such as intrathecal enzyme replacement and hematopoietic stem-cell transplantation (HSCT) associated with gene therapy. […] In short, Metachromatic Leukodystrophy is a rare, devastating, and progressive hereditary disease. Given the possibility of emerging treatments specific to this illness, it is vital to obtain an early diagnosis.

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