Materiały źródłowe

• #1 Homocystinuria – Wikipedia

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

  Homocystinuria (HCU) is an inherited disorder of the metabolism of the amino acid methionine due to a deficiency of cystathionine beta synthase or methionine synthase. Symptoms of homocystinuria can also be caused by a deficiency of vitamins B6, B12, or folate. […] This defect leads to a multi-systemic disorder of the connective tissue, muscles, central nervous system (CNS), and cardiovascular system. Homocystinuria represents a group of hereditary metabolic disorders characterized by an accumulation of the amino acid homocysteine in the serum and an increased excretion of homocysteine in the urine. Infants appear to be normal and early symptoms, if any are present, are vague. […] Signs and symptoms of homocystinuria that may be seen include the following: A family history of homocystinuria, Flush across the cheeks, Tall, thin build resembling Marfanoid habitus, Long limbs (dolichostenomelia), High-arched feet (pes cavus), Knock knees (genu valgum), Pectus excavatum and Pectus carinatum, Intellectual disability, Seizures, Psychiatric disease, Eye anomalies, Vascular disease. […] The life expectancy of patients with homocystinuria is reduced only if untreated. It is known that before the age of 30, almost one quarter of patients die as a result of thrombotic complications (e.g., heart attack).

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• #1 Homocystinuria Information | Mount Sinai – New York

  https://www.mountsinai.org/health-library/diseases-conditions/homocystinuria

  Homocystinuria is a genetic disorder that affects the metabolism of the amino acid methionine. […] Newborn infants appear healthy. Early symptoms, if present, are not obvious. Symptoms may occur as mildly delayed development or failure to thrive. Increasing visual problems may lead to diagnosis of this condition. […] Other symptoms include: Chest deformities (pectus carinatum, pectus excavatum), Flush across the cheeks, High arches of the feet, Intellectual disability, Knock knees, Long limbs, Mental disorders, Nearsightedness, Spidery fingers (arachnodactyly), Tall, thin build. […] Although no cure exists for homocystinuria, vitamin B therapy can help about half of people affected by the condition. If the diagnosis is made in childhood, starting a low-methionine diet quickly may prevent some intellectual disability and other complications of the disease. For this reason, some states screen for homocystinuria in all newborns. […] People whose blood homocysteine levels continue to rise are at increased risk for blood clots. Clots can cause serious medical problems and shorten lifespan. […] Intellectual disability is a serious outcome of the disease. But, it can be reduced if diagnosed early.

• #1 Homocystinuria (HCU): Symptoms, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/25160-homocystinuria

  Homocystinuria symptoms may include: […] The symptoms of the most common type of homocystinuria usually involve your: […] Eyes. […] Dislocation of the lenses of your eyes (ectopia lentis). […] Severe nearsightedness (myopia). […] Skeletal system. […] Excessive growth. […] Long arms, legs, fingers and toes. […] Knees bent inward that touch when legs are straight (knock knees). […] Sunken or protruding chest. […] Curvature of your spine (scoliosis). […] People with homocystinuria are also at risk of developing early osteoporosis. […] Central nervous system. […] Developmental delays. […] Learning problems. […] Vascular system. […] Increased risk of blood clots, which can lead to stroke or pulmonary embolism. […] The symptoms of homocystinuria vary based on which type you have. They typically develop during the first few years of life. But some people dont develop any symptoms until adulthood. […] With early diagnosis and lifelong treatment, most children with homocystinuria can expect to live normal, healthy lives.

• #1 Homocystinuria diagnosis and management: it is not all classical | Journal of Clinical Pathology

  https://jcp.bmj.com/content/75/11/744

  Homocystinuria (HCU) refers to a group of inherited disorders of homocysteine metabolism associated with high blood homocysteine concentration, thromboembolic tendency and neurocognitive symptoms. […] Thromboembolic tendency increases in direct proportion to the magnitude and duration of HCy elevation. Left untreated there’s a 30% chance of a vascular event by age 20 rising to 50% by the age of 30. […] Lens subluxation is a hallmark of HCU distinguishing it from remethylation disorders and is detectable in approximately 70% of untreated patients by the age of 10 and in over 90% diagnosed later. […] Skeletal and connective tissue disorders affect approximately 50% of HCU patients, and may variably include elongated long bones (Marfanoid body habitus), arachnodactyly, joint laxity, osteopenia, scoliosis and vertebral collapse.

• #1 Homocystinuria Caused by Cystathionine Beta-Synthase Deficiency – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK1524/

  Homocystinuria caused by cystathionine -synthase (CBS) deficiency is characterized by involvement of the eye (ectopia lentis and/or severe myopia), skeletal system (excessive height, long limbs, scoliosis, and pectus excavatum), vascular system (thromboembolism), and CNS (developmental delay/intellectual disability). All four or only one of the systems can be involved; expressivity is variable for all of the clinical signs. […] Thromboembolism is the major cause of early death and morbidity. IQ in individuals with untreated homocystinuria ranges widely, from 10 to 138. In B6-responsive individuals the mean IQ is 79 versus 57 for those who are B6-non-responsive. Other features that may occur include: seizures, psychiatric problems, extrapyramidal signs (e.g., dystonia), hypopigmentation of the skin and hair, malar flush, livedo reticularis, and pancreatitis.

• #1 Homocystinuria: Causes, symptoms, and tests

  https://www.medicalnewstoday.com/articles/318526

  In most cases of homocystinuria, the enzyme cystathionine beta-synthase (CBS) is not effective. As a result, the body cannot break down the amino acids methionine and homocysteine. […] The signs and symptoms of homocystinuria become clear in the first year of life. While some infants only experience mild effects, the symptoms may get worse as the individual progresses into childhood and even adulthood. […] Symptoms may include: nearsightedness, dislocation of the lenses of the eyes, pale skin and hair, weak bones, sideways curvature of the spine, long, thin arms and legs, chest deformities, developmental delays and learning disabilities, behavioral problems. […] Many of these symptoms may get worse when a baby consumes food that their body cannot break down. Periods of illness and infection can also trigger these symptoms.

• #1 Orphanet: Homocystinuria due to cystathionine beta-synthase deficiency

  https://www.orpha.net/en/disease/detail/394

  Patients exhibit a spectrum of progressively appearing clinical manifestations, ranging from asymptomatic to severe, with one or multiple organ systems involved. […] Symptoms essentially affect four types of organ: eyes (ectopia lentis), skeletal system (high stature, marfanoid morphotype, skeletal deformations, osteoporosis), vascular system (arterial or veinous thromboembolism), and CNS (developmental delay, autism spectrum disorders, psychiatric disorders). […] The consequences of untreated, or partially treated, CBS deficiency include thromboembolic events, intellectual disability, ocular and skeletal manifestations. Untreated CBS patients showed that the risk of complications increases with age. The prognosis of patients treated from the neonatal period is good, with virtually complete prevention of all abnormalities. In late-treated patients, therapy aims at preventing thromboembolic events and further escalation of the complications.

• #1 Back to Home

  http://m.newbornscreening.info/Parents/aminoaciddisorders/CBS.html

  Babies with homocystinuria look healthy and normal at birth. Over time, if the condition is not treated, it can cause growth and learning delays. It can also affect the eyes, bones, heart, and blood vessels. […] Delays in growth and learning are often noticed between the ages of one and three. Common effects in untreated children include: poor growth, problems gaining weight, delays in crawling, walking, and talking, behavior and emotional problems, serious learning disabilities or intellectual disabilities. […] Children usually start to develop vision problems after one year of age. They develop severe nearsightedness and have trouble seeing objects that are far and not close to them. If this is not treated, the lens of the eye can become loose and move out of place. This is called lens dislocation. This often happens between two and eight years of age. Glaucoma, a condition caused by increased eye pressure, can happen over time if the lens dislocation is not treated. Untreated glaucoma can cause blindness.

• #1 Homocystinuria – EyeWiki

  https://eyewiki.org/Homocystinuria

  If left untreated, 82% of patients will have ectopia lentis by 10 years of age and 27% will have a clinically detectable thromboembolic event by 15 years old. Half of individuals with untreated homocystinuria will have an event before the age of 30 and one predicted event per 25 years at the time of maximal risk. Vascular events remain the major cause of morbidity and mortality in untreated patients. However, appropriate long-term treatment is effective in reducing the potentially life-threatening thromboembolic events and any other complication, ocular, skeletal, or nervous.

• #1 Homocystinuria diagnosis and management: it is not all classical | Journal of Clinical Pathology

  https://jcp.bmj.com/content/75/11/744

  Learning disabilities are not universal or may be subtle and, when present, include global intellectual impairment, specific learning disabilities such as autism and behavioural disturbance. […] The primary goal is to maintain plasma tHCy concentration at less than 100 mol/L in adults and less than 50 mol/L in children at which thromboembolic risk is reversed, lens subluxation is halted and bone growth in children proceeds normally. […] Very early initiation of treatment allows for normal intellectual development, but once learning difficulties are evident they are not reversed by treatment. […] In classical HCU, remethylation is the only route available for HCy metabolism, and consequently, methionine is high and cystine, distal to the defective CBS enzyme, is low. Conversely, in remethylation disorders, CBS is the only route available for HCy metabolism, therefore, methionine is low.

• #1 Betaine anhydrous in homocystinuria: results from the RoCH registry | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-019-1036-2

  Homocystinuria is an autosomal recessive disorder of homocysteine metabolism leading to increased plasma, urine and tissue accumulation of homocysteine and its metabolites. The clinical manifestations of classical homocystinuria include skeletal abnormalities, osteoporosis, ectopia lentis and/or severe myopia, cognitive impairment, developmental delay/intellectual disability, seizures, psychiatric disorders, atherosclerosis and thromboembolism. If untreated, homocystinuria is a serious, life-threatening disease. […] A broad range of clinical presentations associated with homocystinuria were observed during the study period. CBS-deficient vitamin B6 non-responders mainly reported ocular (74.0%), skeletal (72.0%), neurologic (66.0%) and cardiovascular (46.0%) symptoms. Skeletal and cardiovascular issues were reported by 77.8% of CBS-deficient B6 responders, followed by ocular (66.7%) and neurologic (55.6%) abnormalities. The majority of Cbl metabolism-defective patients (80.0%) reported neurologic disorders, followed by ocular and hematologic disorders in 66.7 and 64.4% of patients, respectively. All MTHFR-deficient patients had neurologic impairment, over half (52.4%) had psychiatric disturbances, and skeletal disorders were reported in 38.1% of these patients.

• #1 Homocystinuria (HCY)

  https://www.wadsworth.org/node/2592/printable/print

  There are two types of homocystinuria: vitamin B6 responsive and non-vitamin B6 responsive. The symptoms of vitamin B6 responsive homocystinuria are usually milder. The symptoms of untreated homocystinuria vary from one person to the next, but may include developmental delay, near sightedness (myopia), skeletal abnormalities (long limbs) and increased risk of blood clots (thromboembolism). There is also a risk for a dislocation of the lens in the eye (ectopia lentis). Intellectual disability is usually more severe in untreated non-vitamin B6 responsive homocystinuria. […] On treatment, prognosis is significantly improved.

• #1 Methylmalonic acidemia with homocystinuria: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/methylmalonic-acidemia-with-homocystinuria/

  Methylmalonic acidemia with homocystinuria is a disorder in which the body is unable to correctly process certain protein building blocks (amino acids), fat building blocks (fatty acids), and cholesterol. The signs and symptoms of methylmalonic acidemia with homocystinuria usually develop in infancy, although they can begin at any age. When the condition begins early in life, affected individuals typically grow more slowly than expected. These infants can also have difficulty feeding and have an abnormally pale appearance (pallor). Eye abnormalities and neurological problems, including weak muscle tone (hypotonia) and seizures, are also common in people with methylmalonic acidemia with homocystinuria. Many infants and children with this condition have delayed development and intellectual disability, and some have an unusually small head size (microcephaly).

• #1 SciELO Brazil – Three Main Causes of Homocystinuria: CBS, cblC and MTHFR Deficiency. What do they Have in Common? Three Main Causes of Homocystinuria: CBS, cblC and MTHFR Deficiency. What do they Have in Common?

  https://www.scielo.br/j/jiems/a/5KjZr63wC5Md7t3ZW5SpBhn/

  Good metabolic control from the neonatal period and thereafter is capable to prevent the clinical manifestations of HCU. […] Individuals with cblC deficiency often suffer from a wide range of clinical complications, including developmental, metabolic, hematologic, neurologic, ophthalmologic and dermatologic findings. […] Symptoms include feeding difficulties, hypotonia, failure to thrive, seizures, microcephaly and developmental delay. […] The late-onset of the disease seems rarer than the early-onset form. […] Severe methylenetetrahydrofolate reductase (MTHFR) deficiency is inherited as an autosomal recessive metabolic disorder of folate metabolism caused by mutations in the MTHFR gene on chromosome 1p36.3. […] A classical presentation suggestive of MTHFR deficiency is a neonate with acute neurological distress, including generalized muscular hypotonia, feeding problems, failure to thrive, lethargy, apnea, and eventually microcephaly. […] In summary, MTHFR deficiency is a severe disease primarily affecting the CNS, likely due to the reduced availability of methyl-THF and Met, causing reduced cerebral methylation as suggested by decreased SAM levels in CSF.

• #1 Homocystinuria – ThinkGenetic Foundation

  https://thinkgenetic.org/diseases/homocystinuria/

  The severity of symptoms is related to which gene change, or mutation, a person has. It can also be related to their diet or other factors. […] Women with homocystinuria have a greater risk for blood clots. Blood thinners (anticoagulants) are recommended. Blood thinners can lower the risk for blood clots. […] Starting a low-protein diet as soon as possible is very important. It will help manage the symptoms of homocystinuria. […] Some people with homocystinuria have skeletal defects or eye problems. Surgery may be needed to fix these problems. Care should be taken during surgery in people with this disorder. There is an increased risk of blood clots, which can cause complications.

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• #1 Homocystinuria | Newborn Screening

  https://newbornscreening.hrsa.gov/conditions/homocystinuria

  High levels of homocysteine and methionine can cause blood clots and damage to the brain and eyes. If untreated, this damage leads to the signs and symptoms of the condition. […] Signs of homocystinuria can vary widely and usually start before your baby is 1 year old. Symptoms can result from eating protein-containing foods, including milk, that the body cannot break down or by going long periods without eating. Symptoms can also be brought on by illness or infection. Milder forms of homocystinuria may not appear until later in childhood or adulthood. […] Signs of the condition may include the following: Poor growth, Trouble gaining weight, Nearsightedness (myopia), Dislocation of the lens in the eye (ectopia lentis), Blood clots, Tall height and long limbs, Bone problems, Developmental delay, Behavioral difficulties, Learning difficulties, Seizures.

• #1 Homocystinuria patient and caregiver survey: experiences of diagnosis and patient satisfaction | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-021-01764-x

  Clinically ascertained pyridoxine nonresponsive CBS patients reported significantly more frequently developmental delay and anxiety while responsive CBS patients had more thromboses and pulmonary embolism. […] The delay in diagnosis was largely attributed to doctors ignorance of the disease or to organisational problems. […] The diagnosis was made within a year of the first symptoms in half of the clinically ascertained patients in this survey but it was delayed by more than 15 years in 12.5% patients. […] The patients age at first presentation correlated with the diagnostic delay. […] The survey suggests that treatment of the homocystinurias is not always in line with current recommendations. […] Treatment is easy and effective for pyridoxine-responsive CBS-deficient patients but dietary treatment is difficult for other CBS-deficient patients. […] Treatment is not very effective for patients with RMDs and patients with cobalamin defects may dislike their hydroxocobalamin injections.

• #1 Betaine anhydrous in homocystinuria: results from the RoCH registry | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-019-1036-2

  Overall, clinical symptoms of disorders associated with homocystinuria improved in 28.7% of patients, stabilised in 69.7% of patients and worsened in 1.6% of patients at the end of the study period. Among patients with clinical improvement of symptoms, an improvement of 33.0, 31.5, 26.6 and 13.6% was observed in Cbl metabolism-defective, MTHFR-deficient, CBS-deficient B6 non-responders, and CBS-deficient B6 responders, respectively. Clinical improvement of symptoms was determined by the treating physician at each visit as no change, improvement or worsening compared with previous visits.

• #2 Classical homocystinuria – Genomics Education Programme

  http://www.genomicseducation.hee.nhs.uk/documents/classical-homocystinuria/

  Classical homocystinuria (HCU) is an autosomal recessive disorder caused by a deficiency in cystathionine -synthase (CBS) that results in a defect in the catabolic pathway of the amino acid methionine. […] The severity of symptoms in HCU patients can vary markedly: from completely asymptomatic, to a severe multi-system disease. […] Pyridoxine-responsive patients generally have a milder phenotype and a later onset than those who are pyridoxine-unresponsive. […] Childhood presentation more commonly involves lens dislocation and developmental delay. Onset in adulthood is typically associated with thromboembolism. […] Thromboembolism is the major cause of morbidity and early death for those affected by the condition.

• #2 Homocystinuria – UF Health

  https://ufhealth.org/conditions-and-treatments/homocystinuria

  Newborn infants appear healthy. Early symptoms, if present, are not obvious. […] Symptoms may occur as mildly delayed development or failure to thrive. Increasing visual problems may lead to diagnosis of this condition. […] Other symptoms include: Chest deformities (pectus carinatum, pectus excavatum), Flush across the cheeks, High arches of the feet, Intellectual disability, Knock knees, Long limbs, Mental disorders, Nearsightedness, Spidery fingers (arachnodactyly), Tall, thin build. […] Although no cure exists for homocystinuria, vitamin B therapy can help about half of people affected by the condition. […] If the diagnosis is made in childhood, starting a low-methionine diet quickly may prevent some intellectual disability and other complications of the disease. […] Intellectual disability is a serious outcome of the disease. But, it can be reduced if diagnosed early.

• #2 Homocystinuria – Children’s Health Issues – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/children-s-health-issues/hereditary-metabolic-disorders/homocystinuria

  Homocystinuria is a disorder of amino acid metabolism that is caused by a lack of the enzyme cystathionine beta-synthase, which is needed to metabolize the amino acid homocysteine. This disorder can cause a number of symptoms, including decreased vision, intellectual disability, and skeletal abnormalities. […] Symptoms include intellectual disability, eye problems, and abnormalities of the skeleton. […] Children with homocystinuria are unable to break down (metabolize) the amino acid homocysteine, which, along with certain toxic by-products, builds up to cause a variety of symptoms. Symptoms of homocystinuria range from mild to severe. […] Infants with this disorder are normal at birth. The first symptoms, including dislocation of the lens of the eye causing severely decreased vision, usually begin after 3 years of age.

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  http://www.ncbi.nlm.nih.gov/medgen/199606

  Homocystinuria caused by cystathionine -synthase (CBS) deficiency is characterized by involvement of the eye (ectopia lentis and/or severe myopia), skeletal system (excessive height, long limbs, scoliosis, and pectus excavatum), vascular system (thromboembolism), and CNS (developmental delay/intellectual disability). […] The signs and symptoms of homocystinuria typically develop during childhood, although some mildly affected people may not show signs and symptoms until adulthood. Less common forms of homocystinuria can cause intellectual disability, slower growth and weight gain (failure to thrive), seizures, and problems with movement. […] The most common form of homocystinuria, called classic homocystinuria, is characterized by tall stature, nearsightedness (myopia), dislocation of the lens at the front of the eye, a higher risk of blood clotting disorders, and brittle bones that are prone to fracture (osteoporosis) or other skeletal abnormalities. Some affected individuals also have developmental delay and learning problems.

• #2 What to know about homocystinuria

  https://www.antidote.me/blog/what-to-know-about-homocystinuria

  As a result of this harmful buildup, children with homocystinuria often have a fair complexion, struggle with weight gain, grow too tall too quickly, and have developmental delays. […] Some of the most common symptoms of homocystinuria include: Pale hair and skin, Slow growth, Lens dislocation (also called homocystinuria lens), Weak bones, Blood clots, Seizures, Developmental delays, Learning disabilities, Behavioral and emotional problems.

• #2 Back to Home

  http://m.newbornscreening.info/Parents/aminoaciddisorders/CBS.html

  Babies with homocystinuria look healthy and normal at birth. Over time, if the condition is not treated, it can cause growth and learning delays. It can also affect the eyes, bones, heart, and blood vessels. […] Delays in growth and learning are often noticed between the ages of one and three. Common effects in untreated children include: poor growth, problems gaining weight, delays in crawling, walking, and talking, behavior and emotional problems, serious learning disabilities or intellectual disabilities. […] Children usually start to develop vision problems after one year of age. They develop severe nearsightedness and have trouble seeing objects that are far and not close to them. If this is not treated, the lens of the eye can become loose and move out of place. This is called lens dislocation. This often happens between two and eight years of age. Glaucoma, a condition caused by increased eye pressure, can happen over time if the lens dislocation is not treated. Untreated glaucoma can cause blindness.

• #2 Homocystinuria – EyeWiki

  https://eyewiki.org/Homocystinuria

  If left untreated, 82% of patients will have ectopia lentis by 10 years of age and 27% will have a clinically detectable thromboembolic event by 15 years old. Half of individuals with untreated homocystinuria will have an event before the age of 30 and one predicted event per 25 years at the time of maximal risk. Vascular events remain the major cause of morbidity and mortality in untreated patients. However, appropriate long-term treatment is effective in reducing the potentially life-threatening thromboembolic events and any other complication, ocular, skeletal, or nervous.

• #2 Homocystinuria Caused by Cystathionine Beta-Synthase Deficiency – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK1524/

  The major clinical findings in classic homocystinuria include ectopia lentis (dislocation of the ocular lens) and/or severe myopia, skeletal abnormalities (e.g., excessive height, long narrow limbs [dolichostenomelia], scoliosis, pectus excavatum) that may give the clinical impression of Marfan syndrome, but without joint hypermobility, vascular abnormalities characterized by thromboembolism, and developmental delay/intellectual disability. […] Developmental delay is often the first abnormal sign in individuals with homocystinuria. IQ in individuals with homocystinuria ranges from 10 to 138. B6-responsive individuals are more likely than individuals with B6-non-responsive homocystinuria to be cognitively intact or only mildly affected; the mean IQ of untreated individuals with B6 responsiveness is 79 versus 57 for those who are B6 non-responsive. […] Thromboembolism is the major cause of morbidity and early death.

• #2 MCB Homocystinuria — New England Consortium of Metabolic Programs

  https://www.newenglandconsortium.org/mcb-homocystinuria

  Homocystinuria is a rare metabolic condition in which a chemical called CBS does not work correctly in your body. This can cause two chemicals, homocysteine and methionine, to build up in your blood over time. When these build up too much, they can cause serious health problems. […] Babies with homocystinuria usually have no or few apparent symptoms. Babies and children with homocystinuria who do not get treated for it are at greater risk for serious health problems later in life. Children with this condition may have learning delays, seizures and eye problems. Eye problems can include partial dislocation of the lens, severe nearsightedness, and quivering of the iris. […] Blood clots are a serious health risk for teens and young adults with homocystinuria. You must monitor your blood homocysteine levels to avoid blood clots, which could cause life-threatening blockages to your heart or lungs. Low bone density (osteoporosis) can be a problem for about half of people who have homocystinuria. Some teens or young adults develop scoliosis, a curving of the spine. Osteoporosis often occurs by age 20. Adults with homocystinuria may be at risk for developing serious neurological or mental health problems including depression, anxiety, psychosis, or seizures. Counseling and medication can help. If you have trouble with your mental health, it is important to get in touch with your health care provider to get treatment.

• #2 Newborn screening information for Methylmalonic aciduria with homocystinuria | Baby’s First Test | Newborn Screening | Baby Health

  https://www.babysfirsttest.org/newborn-screening/conditions/methylmalonic-acidemia-with-homocystinuria

  Signs of methylmalonic acidemia with homocystinuria (Cbl C, D, F) could begin anywhere between the first few days of life and 14 years of age. Children with Cbl C usually show symptoms between the first few days and the first month of life. Children with Cbl D deficiency do not show signs until later in childhood. […] If your baby has Cbl C, D, F, you might notice signs including: Delayed growth, Small head size, Skin rash, Vomiting, Poor appetite, Diarrhea, Fever, Sleeping longer or more often, Tiredness, Weak muscle tone (called hypotonia). […] Many of these signs may occur when your baby eats foods that their body cannot break down. They can be triggered by long periods of time without eating, illnesses, and infections. […] Since methylmalonic acidemia with homocystinuria (Cbl C, D, F) is rare, it is not yet certain how effective these dietary and supplement treatments are. It has been recognized that treatments helped some children avoid the signs and symptoms of the condition, whereas they did not help other children. […] It is possible for children with the condition to have learning disabilities, intellectual disabilities, or other complications, even with treatment.

• #2 Betaine anhydrous in homocystinuria: results from the RoCH registry | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-019-1036-2

  Homocystinuria is an autosomal recessive disorder of homocysteine metabolism leading to increased plasma, urine and tissue accumulation of homocysteine and its metabolites. The clinical manifestations of classical homocystinuria include skeletal abnormalities, osteoporosis, ectopia lentis and/or severe myopia, cognitive impairment, developmental delay/intellectual disability, seizures, psychiatric disorders, atherosclerosis and thromboembolism. If untreated, homocystinuria is a serious, life-threatening disease. […] A broad range of clinical presentations associated with homocystinuria were observed during the study period. CBS-deficient vitamin B6 non-responders mainly reported ocular (74.0%), skeletal (72.0%), neurologic (66.0%) and cardiovascular (46.0%) symptoms. Skeletal and cardiovascular issues were reported by 77.8% of CBS-deficient B6 responders, followed by ocular (66.7%) and neurologic (55.6%) abnormalities. The majority of Cbl metabolism-defective patients (80.0%) reported neurologic disorders, followed by ocular and hematologic disorders in 66.7 and 64.4% of patients, respectively. All MTHFR-deficient patients had neurologic impairment, over half (52.4%) had psychiatric disturbances, and skeletal disorders were reported in 38.1% of these patients.

• #2 WV DHHR – OMCFH – Newborn Metabolic Screening – Homocystinuria

  https://www.wvdhhr.org/nbms/diseases/Homocystinuria.asp

  Clinical variability remains despite therapy. Not all affected individuals have increased methionine concentrations. The relationship between variability and the underlying metabolic processes or compliance has not yet been completely ascertained. One described mutation, G307S, is typically a pyridoxine-nonresponsive mutation, and individuals homozygous for the I278T mutation are usually responsive to pyridoxine therapy. The presence of some activity of the enzyme seems necessary for a clinical response to pyridoxine (vitamin B6) administration. Individuals who are clinically responsive to pyridoxine generally have milder or more slowly progressive disease.

• #2 Homocystinuria | Newborn Screening

  https://newbornscreening.hrsa.gov/conditions/homocystinuria

  High levels of homocysteine and methionine can cause blood clots and damage to the brain and eyes. If untreated, this damage leads to the signs and symptoms of the condition. […] Signs of homocystinuria can vary widely and usually start before your baby is 1 year old. Symptoms can result from eating protein-containing foods, including milk, that the body cannot break down or by going long periods without eating. Symptoms can also be brought on by illness or infection. Milder forms of homocystinuria may not appear until later in childhood or adulthood. […] Signs of the condition may include the following: Poor growth, Trouble gaining weight, Nearsightedness (myopia), Dislocation of the lens in the eye (ectopia lentis), Blood clots, Tall height and long limbs, Bone problems, Developmental delay, Behavioral difficulties, Learning difficulties, Seizures.

• #2

  https://www.gov.uk/government/publications/hcu-suspected-description-in-brief/homocystinuria-hcu-detailed-information

  Homocystinuria (pronounced ho-mo-sistin-ur-ee-a), or HCU, is a rare but treatable inherited metabolic disorder that prevents the normal breakdown of protein. […] Untreated HCU can cause long-term health problems, including learning and behavioural difficulties, problems with vision, bone abnormalities, and an increased risk of blood clots and strokes. However, with newborn screening and life-long treatment, these can be prevented. […] With life-long treatment and well controlled homocysteine levels, the outcome is usually very good and most children will avoid any long-term health problems.

• #2 Homocystinuria (HCU): Symptoms, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/25160-homocystinuria

  Homocystinuria symptoms may include: […] The symptoms of the most common type of homocystinuria usually involve your: […] Eyes. […] Dislocation of the lenses of your eyes (ectopia lentis). […] Severe nearsightedness (myopia). […] Skeletal system. […] Excessive growth. […] Long arms, legs, fingers and toes. […] Knees bent inward that touch when legs are straight (knock knees). […] Sunken or protruding chest. […] Curvature of your spine (scoliosis). […] People with homocystinuria are also at risk of developing early osteoporosis. […] Central nervous system. […] Developmental delays. […] Learning problems. […] Vascular system. […] Increased risk of blood clots, which can lead to stroke or pulmonary embolism. […] The symptoms of homocystinuria vary based on which type you have. They typically develop during the first few years of life. But some people dont develop any symptoms until adulthood. […] With early diagnosis and lifelong treatment, most children with homocystinuria can expect to live normal, healthy lives.

• #2 WV DHHR – OMCFH – Newborn Metabolic Screening – Homocystinuria

  https://www.wvdhhr.org/nbms/diseases/Homocystinuria.asp

  Clinical problems include multiple, recurrent thromboemboli. Arterial or venous thromboses may involve the cerebral, pulmonary, renal, and myocardial circulation. Patients may also exhibit ectopia lentis, glaucoma, cataracts, developmental delays/mental retardation, seizures, psychiatric disturbances, osteoporosis with bone deformities, scoliosis, high palatal arch, muscle weakness with a shuffling gait, and a marfanoid habitus. Death has been reported within the first year of life. Approximately 50% of untreated individuals die by 25 years of age; death is frequently a result of thromboembolic events. Developmental delay is reported in 65% to 80% of untreated individuals. […] Two mechanisms probably explain most of the clinical symptoms seen: (1) abnormal (hyper) coagulation because of „sticky” platelets; and (2) direct toxicity of homocystine and its metabolites, causing endothelial cell damage.

• #2 Homocystinuria due to cystathionine beta-synthase deficiency | MedLink Neurology

  https://www.medlink.com/articles/homocystinuria-due-to-cystathionine-beta-synthase-deficiency

  All of the above-mentioned clinical manifestations except for the skeletal manifestation are commonly more pronounced or occur earlier in pyridoxine nonresponsive patients as compared to those who are pyridoxine responsive. […] The outcome in 158 patients treated for up to 18 years has been reported. […] In patients with neonatal diagnosis and treatment, there is also evidence of improved outcome with avoidance of intellectual deficit and dislocation of the lens.

• #2 Betaine anhydrous in homocystinuria: results from the RoCH registry | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-019-1036-2

  Overall, clinical symptoms of disorders associated with homocystinuria improved in 28.7% of patients, stabilised in 69.7% of patients and worsened in 1.6% of patients at the end of the study period. Among patients with clinical improvement of symptoms, an improvement of 33.0, 31.5, 26.6 and 13.6% was observed in Cbl metabolism-defective, MTHFR-deficient, CBS-deficient B6 non-responders, and CBS-deficient B6 responders, respectively. Clinical improvement of symptoms was determined by the treating physician at each visit as no change, improvement or worsening compared with previous visits.

• #3 Homocystinuria: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/homocystinuria/

  Homocystinuria is an inherited disorder in which the body is unable to process certain building blocks of proteins (amino acids) properly. The most common form of homocystinuria, called classic homocystinuria, is characterized by tall stature, nearsightedness (myopia), dislocation of the lens at the front of the eye, a higher risk of blood clotting disorders, and brittle bones that are prone to fracture (osteoporosis) or other skeletal abnormalities. Some affected individuals also have developmental delay and learning problems. […] Less common forms of homocystinuria can cause intellectual disability, slower growth and weight gain (failure to thrive), seizures, and problems with movement. They can also cause and a blood disorder called megaloblastic anemia, which occurs when a person has a low number of red blood cells (anemia), and the remaining red blood cells are larger than normal (megaloblastic). […] The signs and symptoms of homocystinuria typically develop during childhood, although some mildly affected people may not show signs and symptoms until adulthood.

• #3 Homocystinuria diagnosis and management: it is not all classical | Journal of Clinical Pathology

  https://jcp.bmj.com/content/75/11/744

  Homocystinuria (HCU) refers to a group of inherited disorders of homocysteine metabolism associated with high blood homocysteine concentration, thromboembolic tendency and neurocognitive symptoms. […] Thromboembolic tendency increases in direct proportion to the magnitude and duration of HCy elevation. Left untreated there’s a 30% chance of a vascular event by age 20 rising to 50% by the age of 30. […] Lens subluxation is a hallmark of HCU distinguishing it from remethylation disorders and is detectable in approximately 70% of untreated patients by the age of 10 and in over 90% diagnosed later. […] Skeletal and connective tissue disorders affect approximately 50% of HCU patients, and may variably include elongated long bones (Marfanoid body habitus), arachnodactyly, joint laxity, osteopenia, scoliosis and vertebral collapse.

• #3 Homocystinuria (HCU): Symptoms, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/25160-homocystinuria

  Homocystinuria symptoms may include: […] The symptoms of the most common type of homocystinuria usually involve your: […] Eyes. […] Dislocation of the lenses of your eyes (ectopia lentis). […] Severe nearsightedness (myopia). […] Skeletal system. […] Excessive growth. […] Long arms, legs, fingers and toes. […] Knees bent inward that touch when legs are straight (knock knees). […] Sunken or protruding chest. […] Curvature of your spine (scoliosis). […] People with homocystinuria are also at risk of developing early osteoporosis. […] Central nervous system. […] Developmental delays. […] Learning problems. […] Vascular system. […] Increased risk of blood clots, which can lead to stroke or pulmonary embolism. […] The symptoms of homocystinuria vary based on which type you have. They typically develop during the first few years of life. But some people dont develop any symptoms until adulthood. […] With early diagnosis and lifelong treatment, most children with homocystinuria can expect to live normal, healthy lives.

• #3 What Is Homocystinuria?

  https://www.webmd.com/children/what-is-homocystinuria

  Babies born with homocystinuria look perfectly fine. Signs and symptoms start to show up within the first few years of life. […] HCY affects all kids differently. If your child has it, they may have many or none of these symptoms: Pale hair and skin, Abnormally-shaped chest, Slow weight gain and growth, Severe nearsightedness and lens dislocation (which can lead to blindness), Tall, slender build, Long, skinny fingers, Weak bones, Blood clots (increasing the risk for stroke and heart disease), Seizures. […] Other symptoms may include: Developmental delays (slow to crawl, walk, and talk), Learning disabilities and intellectual issues, Behavior and emotional problems. […] If your child begins treatment as a baby and stays on it, theyll probably grow and develop normally. Treatment also can lower the risk of strokes, heart disease, and blood clots. Vision problems may still happen even with treatment. These can be fixed with surgery or other methods.

• #3 Homocystinuria | Newborn Screening

  https://newbornscreening.hrsa.gov/conditions/homocystinuria

  High levels of homocysteine and methionine can cause blood clots and damage to the brain and eyes. If untreated, this damage leads to the signs and symptoms of the condition. […] Signs of homocystinuria can vary widely and usually start before your baby is 1 year old. Symptoms can result from eating protein-containing foods, including milk, that the body cannot break down or by going long periods without eating. Symptoms can also be brought on by illness or infection. Milder forms of homocystinuria may not appear until later in childhood or adulthood. […] Signs of the condition may include the following: Poor growth, Trouble gaining weight, Nearsightedness (myopia), Dislocation of the lens in the eye (ectopia lentis), Blood clots, Tall height and long limbs, Bone problems, Developmental delay, Behavioral difficulties, Learning difficulties, Seizures.

• #3 Back to Home

  http://m.newbornscreening.info/Parents/aminoaciddisorders/CBS.html

  Babies with homocystinuria look healthy and normal at birth. Over time, if the condition is not treated, it can cause growth and learning delays. It can also affect the eyes, bones, heart, and blood vessels. […] Delays in growth and learning are often noticed between the ages of one and three. Common effects in untreated children include: poor growth, problems gaining weight, delays in crawling, walking, and talking, behavior and emotional problems, serious learning disabilities or intellectual disabilities. […] Children usually start to develop vision problems after one year of age. They develop severe nearsightedness and have trouble seeing objects that are far and not close to them. If this is not treated, the lens of the eye can become loose and move out of place. This is called lens dislocation. This often happens between two and eight years of age. Glaucoma, a condition caused by increased eye pressure, can happen over time if the lens dislocation is not treated. Untreated glaucoma can cause blindness.

• #3 Homocystinuria – EyeWiki

  https://eyewiki.org/Homocystinuria

  If left untreated, 82% of patients will have ectopia lentis by 10 years of age and 27% will have a clinically detectable thromboembolic event by 15 years old. Half of individuals with untreated homocystinuria will have an event before the age of 30 and one predicted event per 25 years at the time of maximal risk. Vascular events remain the major cause of morbidity and mortality in untreated patients. However, appropriate long-term treatment is effective in reducing the potentially life-threatening thromboembolic events and any other complication, ocular, skeletal, or nervous.

• #3 WV DHHR – OMCFH – Newborn Metabolic Screening – Homocystinuria

  https://www.wvdhhr.org/nbms/diseases/Homocystinuria.asp

  Clinical problems include multiple, recurrent thromboemboli. Arterial or venous thromboses may involve the cerebral, pulmonary, renal, and myocardial circulation. Patients may also exhibit ectopia lentis, glaucoma, cataracts, developmental delays/mental retardation, seizures, psychiatric disturbances, osteoporosis with bone deformities, scoliosis, high palatal arch, muscle weakness with a shuffling gait, and a marfanoid habitus. Death has been reported within the first year of life. Approximately 50% of untreated individuals die by 25 years of age; death is frequently a result of thromboembolic events. Developmental delay is reported in 65% to 80% of untreated individuals. […] Two mechanisms probably explain most of the clinical symptoms seen: (1) abnormal (hyper) coagulation because of „sticky” platelets; and (2) direct toxicity of homocystine and its metabolites, causing endothelial cell damage.

• #3 MCB Homocystinuria — New England Consortium of Metabolic Programs

  https://www.newenglandconsortium.org/mcb-homocystinuria

  Homocystinuria is a rare metabolic condition in which a chemical called CBS does not work correctly in your body. This can cause two chemicals, homocysteine and methionine, to build up in your blood over time. When these build up too much, they can cause serious health problems. […] Babies with homocystinuria usually have no or few apparent symptoms. Babies and children with homocystinuria who do not get treated for it are at greater risk for serious health problems later in life. Children with this condition may have learning delays, seizures and eye problems. Eye problems can include partial dislocation of the lens, severe nearsightedness, and quivering of the iris. […] Blood clots are a serious health risk for teens and young adults with homocystinuria. You must monitor your blood homocysteine levels to avoid blood clots, which could cause life-threatening blockages to your heart or lungs. Low bone density (osteoporosis) can be a problem for about half of people who have homocystinuria. Some teens or young adults develop scoliosis, a curving of the spine. Osteoporosis often occurs by age 20. Adults with homocystinuria may be at risk for developing serious neurological or mental health problems including depression, anxiety, psychosis, or seizures. Counseling and medication can help. If you have trouble with your mental health, it is important to get in touch with your health care provider to get treatment.

• #3 Betaine anhydrous in homocystinuria: results from the RoCH registry | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-019-1036-2

  Homocystinuria is an autosomal recessive disorder of homocysteine metabolism leading to increased plasma, urine and tissue accumulation of homocysteine and its metabolites. The clinical manifestations of classical homocystinuria include skeletal abnormalities, osteoporosis, ectopia lentis and/or severe myopia, cognitive impairment, developmental delay/intellectual disability, seizures, psychiatric disorders, atherosclerosis and thromboembolism. If untreated, homocystinuria is a serious, life-threatening disease. […] A broad range of clinical presentations associated with homocystinuria were observed during the study period. CBS-deficient vitamin B6 non-responders mainly reported ocular (74.0%), skeletal (72.0%), neurologic (66.0%) and cardiovascular (46.0%) symptoms. Skeletal and cardiovascular issues were reported by 77.8% of CBS-deficient B6 responders, followed by ocular (66.7%) and neurologic (55.6%) abnormalities. The majority of Cbl metabolism-defective patients (80.0%) reported neurologic disorders, followed by ocular and hematologic disorders in 66.7 and 64.4% of patients, respectively. All MTHFR-deficient patients had neurologic impairment, over half (52.4%) had psychiatric disturbances, and skeletal disorders were reported in 38.1% of these patients.

• #3 Methylmalonic acidemia with homocystinuria: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/methylmalonic-acidemia-with-homocystinuria/

  Methylmalonic acidemia with homocystinuria is a disorder in which the body is unable to correctly process certain protein building blocks (amino acids), fat building blocks (fatty acids), and cholesterol. The signs and symptoms of methylmalonic acidemia with homocystinuria usually develop in infancy, although they can begin at any age. When the condition begins early in life, affected individuals typically grow more slowly than expected. These infants can also have difficulty feeding and have an abnormally pale appearance (pallor). Eye abnormalities and neurological problems, including weak muscle tone (hypotonia) and seizures, are also common in people with methylmalonic acidemia with homocystinuria. Many infants and children with this condition have delayed development and intellectual disability, and some have an unusually small head size (microcephaly).

• #3 SciELO Brazil – Three Main Causes of Homocystinuria: CBS, cblC and MTHFR Deficiency. What do they Have in Common? Three Main Causes of Homocystinuria: CBS, cblC and MTHFR Deficiency. What do they Have in Common?

  https://www.scielo.br/j/jiems/a/5KjZr63wC5Md7t3ZW5SpBhn/

  Good metabolic control from the neonatal period and thereafter is capable to prevent the clinical manifestations of HCU. […] Individuals with cblC deficiency often suffer from a wide range of clinical complications, including developmental, metabolic, hematologic, neurologic, ophthalmologic and dermatologic findings. […] Symptoms include feeding difficulties, hypotonia, failure to thrive, seizures, microcephaly and developmental delay. […] The late-onset of the disease seems rarer than the early-onset form. […] Severe methylenetetrahydrofolate reductase (MTHFR) deficiency is inherited as an autosomal recessive metabolic disorder of folate metabolism caused by mutations in the MTHFR gene on chromosome 1p36.3. […] A classical presentation suggestive of MTHFR deficiency is a neonate with acute neurological distress, including generalized muscular hypotonia, feeding problems, failure to thrive, lethargy, apnea, and eventually microcephaly. […] In summary, MTHFR deficiency is a severe disease primarily affecting the CNS, likely due to the reduced availability of methyl-THF and Met, causing reduced cerebral methylation as suggested by decreased SAM levels in CSF.

• #3 WV DHHR – OMCFH – Newborn Metabolic Screening – Homocystinuria

  https://www.wvdhhr.org/nbms/diseases/Homocystinuria.asp

  Clinical variability remains despite therapy. Not all affected individuals have increased methionine concentrations. The relationship between variability and the underlying metabolic processes or compliance has not yet been completely ascertained. One described mutation, G307S, is typically a pyridoxine-nonresponsive mutation, and individuals homozygous for the I278T mutation are usually responsive to pyridoxine therapy. The presence of some activity of the enzyme seems necessary for a clinical response to pyridoxine (vitamin B6) administration. Individuals who are clinically responsive to pyridoxine generally have milder or more slowly progressive disease.

• #3 Homocystinuria patient and caregiver survey: experiences of diagnosis and patient satisfaction | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-021-01764-x

  Clinically ascertained pyridoxine nonresponsive CBS patients reported significantly more frequently developmental delay and anxiety while responsive CBS patients had more thromboses and pulmonary embolism. […] The delay in diagnosis was largely attributed to doctors ignorance of the disease or to organisational problems. […] The diagnosis was made within a year of the first symptoms in half of the clinically ascertained patients in this survey but it was delayed by more than 15 years in 12.5% patients. […] The patients age at first presentation correlated with the diagnostic delay. […] The survey suggests that treatment of the homocystinurias is not always in line with current recommendations. […] Treatment is easy and effective for pyridoxine-responsive CBS-deficient patients but dietary treatment is difficult for other CBS-deficient patients. […] Treatment is not very effective for patients with RMDs and patients with cobalamin defects may dislike their hydroxocobalamin injections.

• #3 Homocystinuria/Homocysteinemia: Overview, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/1115062-clinical

  Homocystinuria is associated with the following physical findings: Downward dislocation of lens (ectopia lentis), Marfanoid habitus, Pes excavatum, pes carinatum, and genu valgum, Intellectual disability, Signs and symptoms of strokes in any vascular distribution: hemiplegia, aphasia, ataxia, and pseudobulbar palsy are among the most common findings. […] Patients with classic homocystinuria may first be recognized because of downward dislocation of the lens (ectopia lentis), marfanoid habitus, intellectual disability, and/or seizures. […] Acute stroke symptoms may occur in these patients. […] Early diagnosis of homocystinuria along with prophylactic medical and dietary care is a key to better long-term prognosis; it can halt or even reverse some of the complications. […] Patients with homocystinuria are prone to thromboembolic events in the perioperative and postoperative periods, even with minor surgeries.

• #3

  https://www.gov.uk/government/publications/hcu-suspected-description-in-brief/homocystinuria-hcu-detailed-information

  Homocystinuria (pronounced ho-mo-sistin-ur-ee-a), or HCU, is a rare but treatable inherited metabolic disorder that prevents the normal breakdown of protein. […] Untreated HCU can cause long-term health problems, including learning and behavioural difficulties, problems with vision, bone abnormalities, and an increased risk of blood clots and strokes. However, with newborn screening and life-long treatment, these can be prevented. […] With life-long treatment and well controlled homocysteine levels, the outcome is usually very good and most children will avoid any long-term health problems.

• #3 Homocystinuria

  https://dermnetnz.org/topics/homocystinuria

  Newborns with homocystinuria often appear normal, but signs and symptoms begin to develop in the first year of life, though they are not all obvious at first. […] Signs and symptoms of homocystinuria may vary widely, and patients can present with any of the following: Marfanoid appearance (this refers to the tall, thin build and long-limbed appearance reminiscent of Marfan syndrome), Pectus carinatum or pectus excavatum (the depression of protrusion of the sternum), High, arched palate with crowding of the teeth, Kyphoscoliosis, Ectopic lentis (dislocation of the lens), Myopia, Glaucoma, Intellectual disability (with an average IQ of 80, although approximately 30% of patients with homocystinuria have IQs in the normal range), Arachnodactyly (long, spidery fingers), Seizures, Cerebrovascular events, Psychiatric disorders, Osteoporosis, Infant failure to thrive, Increased chance of blood clot formation and for deep vein thrombosis. […] Many patients with homocystinuria die as young adults due to arterial and venous thrombosis.

• #3 Betaine anhydrous in homocystinuria: results from the RoCH registry | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-019-1036-2

  Overall, clinical symptoms of disorders associated with homocystinuria improved in 28.7% of patients, stabilised in 69.7% of patients and worsened in 1.6% of patients at the end of the study period. Among patients with clinical improvement of symptoms, an improvement of 33.0, 31.5, 26.6 and 13.6% was observed in Cbl metabolism-defective, MTHFR-deficient, CBS-deficient B6 non-responders, and CBS-deficient B6 responders, respectively. Clinical improvement of symptoms was determined by the treating physician at each visit as no change, improvement or worsening compared with previous visits.

• #4 Homocystinuria: Causes, Symptoms & Diagnosis

  https://www.healthline.com/health/homocystinuria

  The illness usually affects infants during the first few years of life, and the more rare forms of the disorder can lead to children being underweight. If its left untreated, homocystinuria can have serious and sometimes fatal complications. […] The symptoms will depend on the type of homocystinuria. Symptoms generally develop during the first years of life. However, some people experience symptoms during adulthood. Symptoms are often vague and difficult to detect. The most common forms of this disorder may involve the following symptoms: dislocation of the lenses in the eyes, nearsightedness, abnormal blood clots, osteoporosis, or weakening of the bones, learning disabilities, developmental problems, chest deformities, such as a protrusion or a caved-in appearance of the breastbone, long, spindly arms and legs, scoliosis.

• #4 What Is Homocystinuria?

  https://www.webmd.com/children/what-is-homocystinuria

  Babies born with homocystinuria look perfectly fine. Signs and symptoms start to show up within the first few years of life. […] HCY affects all kids differently. If your child has it, they may have many or none of these symptoms: Pale hair and skin, Abnormally-shaped chest, Slow weight gain and growth, Severe nearsightedness and lens dislocation (which can lead to blindness), Tall, slender build, Long, skinny fingers, Weak bones, Blood clots (increasing the risk for stroke and heart disease), Seizures. […] Other symptoms may include: Developmental delays (slow to crawl, walk, and talk), Learning disabilities and intellectual issues, Behavior and emotional problems. […] If your child begins treatment as a baby and stays on it, theyll probably grow and develop normally. Treatment also can lower the risk of strokes, heart disease, and blood clots. Vision problems may still happen even with treatment. These can be fixed with surgery or other methods.

• #4 Homocystinuria Caused by Cystathionine Beta-Synthase Deficiency – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK1524/

  Homocystinuria caused by cystathionine -synthase (CBS) deficiency is characterized by involvement of the eye (ectopia lentis and/or severe myopia), skeletal system (excessive height, long limbs, scoliosis, and pectus excavatum), vascular system (thromboembolism), and CNS (developmental delay/intellectual disability). All four or only one of the systems can be involved; expressivity is variable for all of the clinical signs. […] Thromboembolism is the major cause of early death and morbidity. IQ in individuals with untreated homocystinuria ranges widely, from 10 to 138. In B6-responsive individuals the mean IQ is 79 versus 57 for those who are B6-non-responsive. Other features that may occur include: seizures, psychiatric problems, extrapyramidal signs (e.g., dystonia), hypopigmentation of the skin and hair, malar flush, livedo reticularis, and pancreatitis.

• #4 Back to Home

  http://m.newbornscreening.info/Parents/aminoaciddisorders/CBS.html

  Babies with homocystinuria look healthy and normal at birth. Over time, if the condition is not treated, it can cause growth and learning delays. It can also affect the eyes, bones, heart, and blood vessels. […] Delays in growth and learning are often noticed between the ages of one and three. Common effects in untreated children include: poor growth, problems gaining weight, delays in crawling, walking, and talking, behavior and emotional problems, serious learning disabilities or intellectual disabilities. […] Children usually start to develop vision problems after one year of age. They develop severe nearsightedness and have trouble seeing objects that are far and not close to them. If this is not treated, the lens of the eye can become loose and move out of place. This is called lens dislocation. This often happens between two and eight years of age. Glaucoma, a condition caused by increased eye pressure, can happen over time if the lens dislocation is not treated. Untreated glaucoma can cause blindness.

• #4

  https://omim.org/entry/236200

  Classic homocystinuria is an autosomal recessive metabolic disorder of sulfur metabolism. The clinical features of untreated homocystinuria due to CBS deficiency usually manifest in the first or second decade of life and include myopia, ectopia lentis, mental retardation, skeletal anomalies resembling Marfan syndrome (MFS; 154700), and thromboembolic events. […] Some patients have been reported to have a milder form of homocystinuria, which is characterized by increased plasma homocysteine and increased risk for thrombotic events in young adulthood, but without the other skeletal, ocular, or nervous system manifestations observed in classic homocystinuria (Kelly et al., 2003). […] Thromboembolic events are the most common cause of death in patients with classic homocystinuria and can manifest as peripheral vein thrombosis, pulmonary embolism, stroke, peripheral artery occlusion, and myocardial infarction. The risk of having a vascular event is 25% before age 16 years and 50% by age 30 years.

• #4 Current and Novel Therapeutical Approaches of Classical Homocystinuria in Childhood With Special Focus on Enzyme Replacement Therapy, Liver-Directed Therapy and Gene Therapy | Bittmann | Journal of Clinical Medicine Research

  https://www.jocmr.org/index.php/JOCMR/article/view/4843/25893677

  Overall, the disease is a defect in methionine metabolism. […] Cystathionine beta deficiency presents with many different symptoms and pathological features, particularly affecting the eye, skeleton deformities, central nervous system (CNS) disturbances and vascular diseases. At birth, the children are still normal. If untreated, the disease is progressive. Symptoms in the eyes, an ocular hallmark, include ectopia lentis (50% of cases) with disruption of zonular fasers and high-grade myopia. Skeletal symptoms include genu valgum, dolichostenomelia, moreover pectus excavatum or carinatum, and osteoporosis. The most prominent cause of morbidity and mortality is thromboembolism of the great and small arteries and veins. Decreased intelligence rarely becomes manifest in the first or second year of life. Clinically significant psychiatric problems are present in 50% of patients. However, other organs, including the liver, hair, and skin, also show symptoms of the disease.

• #4 Classical homocystinuria – Genomics Education Programme

  http://www.genomicseducation.hee.nhs.uk/documents/classical-homocystinuria/

  Classical homocystinuria (HCU) is an autosomal recessive disorder caused by a deficiency in cystathionine -synthase (CBS) that results in a defect in the catabolic pathway of the amino acid methionine. […] The severity of symptoms in HCU patients can vary markedly: from completely asymptomatic, to a severe multi-system disease. […] Pyridoxine-responsive patients generally have a milder phenotype and a later onset than those who are pyridoxine-unresponsive. […] Childhood presentation more commonly involves lens dislocation and developmental delay. Onset in adulthood is typically associated with thromboembolism. […] Thromboembolism is the major cause of morbidity and early death for those affected by the condition.

• #4 Newborn screening information for Methylmalonic aciduria with homocystinuria | Baby’s First Test | Newborn Screening | Baby Health

  https://www.babysfirsttest.org/newborn-screening/conditions/methylmalonic-acidemia-with-homocystinuria

  Signs of methylmalonic acidemia with homocystinuria (Cbl C, D, F) could begin anywhere between the first few days of life and 14 years of age. Children with Cbl C usually show symptoms between the first few days and the first month of life. Children with Cbl D deficiency do not show signs until later in childhood. […] If your baby has Cbl C, D, F, you might notice signs including: Delayed growth, Small head size, Skin rash, Vomiting, Poor appetite, Diarrhea, Fever, Sleeping longer or more often, Tiredness, Weak muscle tone (called hypotonia). […] Many of these signs may occur when your baby eats foods that their body cannot break down. They can be triggered by long periods of time without eating, illnesses, and infections. […] Since methylmalonic acidemia with homocystinuria (Cbl C, D, F) is rare, it is not yet certain how effective these dietary and supplement treatments are. It has been recognized that treatments helped some children avoid the signs and symptoms of the condition, whereas they did not help other children. […] It is possible for children with the condition to have learning disabilities, intellectual disabilities, or other complications, even with treatment.

• #4 WV DHHR – OMCFH – Newborn Metabolic Screening – Homocystinuria

  https://www.wvdhhr.org/nbms/diseases/Homocystinuria.asp

  Clinical variability remains despite therapy. Not all affected individuals have increased methionine concentrations. The relationship between variability and the underlying metabolic processes or compliance has not yet been completely ascertained. One described mutation, G307S, is typically a pyridoxine-nonresponsive mutation, and individuals homozygous for the I278T mutation are usually responsive to pyridoxine therapy. The presence of some activity of the enzyme seems necessary for a clinical response to pyridoxine (vitamin B6) administration. Individuals who are clinically responsive to pyridoxine generally have milder or more slowly progressive disease.

• #4 Homocystinuria – ThinkGenetic Foundation

  https://thinkgenetic.org/diseases/homocystinuria/

  The severity of symptoms is related to which gene change, or mutation, a person has. It can also be related to their diet or other factors. […] Women with homocystinuria have a greater risk for blood clots. Blood thinners (anticoagulants) are recommended. Blood thinners can lower the risk for blood clots. […] Starting a low-protein diet as soon as possible is very important. It will help manage the symptoms of homocystinuria. […] Some people with homocystinuria have skeletal defects or eye problems. Surgery may be needed to fix these problems. Care should be taken during surgery in people with this disorder. There is an increased risk of blood clots, which can cause complications.

• #4

• #4 Homocystinuria – EyeWiki

  https://eyewiki.org/Homocystinuria

  If left untreated, 82% of patients will have ectopia lentis by 10 years of age and 27% will have a clinically detectable thromboembolic event by 15 years old. Half of individuals with untreated homocystinuria will have an event before the age of 30 and one predicted event per 25 years at the time of maximal risk. Vascular events remain the major cause of morbidity and mortality in untreated patients. However, appropriate long-term treatment is effective in reducing the potentially life-threatening thromboembolic events and any other complication, ocular, skeletal, or nervous.

• #4 Homocystinuria – Wikipedia

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

  Homocystinuria (HCU) is an inherited disorder of the metabolism of the amino acid methionine due to a deficiency of cystathionine beta synthase or methionine synthase. Symptoms of homocystinuria can also be caused by a deficiency of vitamins B6, B12, or folate. […] This defect leads to a multi-systemic disorder of the connective tissue, muscles, central nervous system (CNS), and cardiovascular system. Homocystinuria represents a group of hereditary metabolic disorders characterized by an accumulation of the amino acid homocysteine in the serum and an increased excretion of homocysteine in the urine. Infants appear to be normal and early symptoms, if any are present, are vague. […] Signs and symptoms of homocystinuria that may be seen include the following: A family history of homocystinuria, Flush across the cheeks, Tall, thin build resembling Marfanoid habitus, Long limbs (dolichostenomelia), High-arched feet (pes cavus), Knock knees (genu valgum), Pectus excavatum and Pectus carinatum, Intellectual disability, Seizures, Psychiatric disease, Eye anomalies, Vascular disease. […] The life expectancy of patients with homocystinuria is reduced only if untreated. It is known that before the age of 30, almost one quarter of patients die as a result of thrombotic complications (e.g., heart attack).

• #4 Homocystinuria patient and caregiver survey: experiences of diagnosis and patient satisfaction | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-021-01764-x

  Clinically ascertained pyridoxine nonresponsive CBS patients reported significantly more frequently developmental delay and anxiety while responsive CBS patients had more thromboses and pulmonary embolism. […] The delay in diagnosis was largely attributed to doctors ignorance of the disease or to organisational problems. […] The diagnosis was made within a year of the first symptoms in half of the clinically ascertained patients in this survey but it was delayed by more than 15 years in 12.5% patients. […] The patients age at first presentation correlated with the diagnostic delay. […] The survey suggests that treatment of the homocystinurias is not always in line with current recommendations. […] Treatment is easy and effective for pyridoxine-responsive CBS-deficient patients but dietary treatment is difficult for other CBS-deficient patients. […] Treatment is not very effective for patients with RMDs and patients with cobalamin defects may dislike their hydroxocobalamin injections.

• #4 Newborn screening information for homocystinuria | Baby’s First Test | Newborn Screening | Baby Health

  https://www.babysfirsttest.org/newborn-screening/conditions/homocystinuria

  Babies with homocystinuria (HCY) are usually healthy at birth. Early screening and treatment can often prevent the signs and symptoms of HCY. If children are not treated, signs of HCY usually begin between ages one and three. The signs and symptoms are highly variable among individuals with HCY. Your baby may have many of these signs or none at all. […] Signs of HCY may include: Poor growth, Trouble gaining weight, Developmental delays, Behavioral difficulties, Weak muscle tone (also known as hypotonia), Pale skin and hair, Seizures (Epilepsy). […] With early and on-going treatment, children with homocystinuria (HCY) can have healthy growth and development. Treatment can reduce the chances for developing blood clots, vision trouble, heart disease, and strokes. […] Some children who receive treatment still experience vision trouble, but this can be corrected. […] Children who do not receive treatment for HCY may develop behavioral difficulties, learning disabilities, or intellectual disabilities.

• #5 Homocystinuria – ThinkGenetic Foundation

  https://thinkgenetic.org/diseases/homocystinuria/

  Some people with homocystinuria have intellectual problems and some of them do not. […] Symptoms include problems with the eyes, skeletal system, blood, and brain. Symptoms can vary and not all affected people have all of the findings. The severity of the symptoms can also vary. Some people with a mild form may not show symptoms until childhood or adulthood. People with severe forms can show symptoms as babies. […] High levels of homocysteine in the body can lead to many different health problems. […] The symptoms of homocystinuria can vary a lot from person to person. Some people only have very mild signs of the disorder. Some people may have many health problems. In severe cases, the health problems may be life threatening. […] The best results for both types are seen in people who are diagnosed early and treated from birth.

• #5 Homocystinuria

  https://dermnetnz.org/topics/homocystinuria

  Newborns with homocystinuria often appear normal, but signs and symptoms begin to develop in the first year of life, though they are not all obvious at first. […] Signs and symptoms of homocystinuria may vary widely, and patients can present with any of the following: Marfanoid appearance (this refers to the tall, thin build and long-limbed appearance reminiscent of Marfan syndrome), Pectus carinatum or pectus excavatum (the depression of protrusion of the sternum), High, arched palate with crowding of the teeth, Kyphoscoliosis, Ectopic lentis (dislocation of the lens), Myopia, Glaucoma, Intellectual disability (with an average IQ of 80, although approximately 30% of patients with homocystinuria have IQs in the normal range), Arachnodactyly (long, spidery fingers), Seizures, Cerebrovascular events, Psychiatric disorders, Osteoporosis, Infant failure to thrive, Increased chance of blood clot formation and for deep vein thrombosis. […] Many patients with homocystinuria die as young adults due to arterial and venous thrombosis.

• #5 Homocystinuria Information | Mount Sinai – New York

  https://www.mountsinai.org/health-library/diseases-conditions/homocystinuria

  Homocystinuria is a genetic disorder that affects the metabolism of the amino acid methionine. […] Newborn infants appear healthy. Early symptoms, if present, are not obvious. Symptoms may occur as mildly delayed development or failure to thrive. Increasing visual problems may lead to diagnosis of this condition. […] Other symptoms include: Chest deformities (pectus carinatum, pectus excavatum), Flush across the cheeks, High arches of the feet, Intellectual disability, Knock knees, Long limbs, Mental disorders, Nearsightedness, Spidery fingers (arachnodactyly), Tall, thin build. […] Although no cure exists for homocystinuria, vitamin B therapy can help about half of people affected by the condition. If the diagnosis is made in childhood, starting a low-methionine diet quickly may prevent some intellectual disability and other complications of the disease. For this reason, some states screen for homocystinuria in all newborns. […] People whose blood homocysteine levels continue to rise are at increased risk for blood clots. Clots can cause serious medical problems and shorten lifespan. […] Intellectual disability is a serious outcome of the disease. But, it can be reduced if diagnosed early.

• #5 Homocystinuria – EyeWiki

  https://eyewiki.org/Homocystinuria

  Homocystinuria is an autosomal recessive inborn error of amino acid metabolism that results in inability to break down homocysteine to cystathionine due to deficiency in the enzyme cystathionine beta-synthase. Homocysteine is toxic to cells, so its accumulation can lead to abnormalities in the eye, skeletal system, vascular system, and central nervous system. Common clinical manifestations include ectopia lentis, developmental delay, marfanoid habitus, and thromboembolism. […] Individuals with homocystinuria can present with any number of different systemic manifestations. In about 50% of patients, the skeletal system is affected, resulting in a Marfanoid habitus which includes excessive height, long limbs, scoliosis, and pectus excavatum. The central nervous system is often involved, presenting with developmental delay, intellectual disability, movement disorders, and seizures.

• #5 Homocystinuria Caused by Cystathionine Beta-Synthase Deficiency – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK1524/

  Homocystinuria caused by cystathionine -synthase (CBS) deficiency is characterized by involvement of the eye (ectopia lentis and/or severe myopia), skeletal system (excessive height, long limbs, scoliosis, and pectus excavatum), vascular system (thromboembolism), and CNS (developmental delay/intellectual disability). All four or only one of the systems can be involved; expressivity is variable for all of the clinical signs. […] Thromboembolism is the major cause of early death and morbidity. IQ in individuals with untreated homocystinuria ranges widely, from 10 to 138. In B6-responsive individuals the mean IQ is 79 versus 57 for those who are B6-non-responsive. Other features that may occur include: seizures, psychiatric problems, extrapyramidal signs (e.g., dystonia), hypopigmentation of the skin and hair, malar flush, livedo reticularis, and pancreatitis.

• #5 Homocystinuria – UF Health

  https://ufhealth.org/conditions-and-treatments/homocystinuria

  Newborn infants appear healthy. Early symptoms, if present, are not obvious. […] Symptoms may occur as mildly delayed development or failure to thrive. Increasing visual problems may lead to diagnosis of this condition. […] Other symptoms include: Chest deformities (pectus carinatum, pectus excavatum), Flush across the cheeks, High arches of the feet, Intellectual disability, Knock knees, Long limbs, Mental disorders, Nearsightedness, Spidery fingers (arachnodactyly), Tall, thin build. […] Although no cure exists for homocystinuria, vitamin B therapy can help about half of people affected by the condition. […] If the diagnosis is made in childhood, starting a low-methionine diet quickly may prevent some intellectual disability and other complications of the disease. […] Intellectual disability is a serious outcome of the disease. But, it can be reduced if diagnosed early.

• #5 Homocystinuria

  https://webeye.ophth.uiowa.edu/eyeforum/cases/269-Homocystinuria.htm

  Ectopia lentis is prevalent in patients with homocystinuria. This is thought to be due to broken and matted zonular fibers that tend to break centrally and curl up against the lens. […] Many patients with homocystinuria also develop nystagmus early on in life. […] Other ocular signs include progressive myopia, strabismus, iridodonesis, cataract, iris atrophy, retinal detachment, central retinal artery occlusion, optic atrophy, anterior staphylomas, sluggish pupillary response, and eyelid clonus. […] There are many systemic signs and symptoms that are manifest with homocystinuria, such as developmental delay, failure to thrive, dental abnormalities, arachnodactyly, thromboembolic events, seizures, megaloblastic anemia, hypotonia, and feeding problems. […] Homocystinuria is treated with vitamin supplementation and dietary restrictions. For patients with the cb1G defect, like the patient in this case, parenteral cobalamin supplementation is indicated as well as betaine supplementation, which acts as a methyl donor in the conversion of homocysteine to methionine.

• #5 Homocystinuria/Homocysteinemia: Overview, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/1115062-clinical

  Homocystinuria is associated with the following physical findings: Downward dislocation of lens (ectopia lentis), Marfanoid habitus, Pes excavatum, pes carinatum, and genu valgum, Intellectual disability, Signs and symptoms of strokes in any vascular distribution: hemiplegia, aphasia, ataxia, and pseudobulbar palsy are among the most common findings. […] Patients with classic homocystinuria may first be recognized because of downward dislocation of the lens (ectopia lentis), marfanoid habitus, intellectual disability, and/or seizures. […] Acute stroke symptoms may occur in these patients. […] Early diagnosis of homocystinuria along with prophylactic medical and dietary care is a key to better long-term prognosis; it can halt or even reverse some of the complications. […] Patients with homocystinuria are prone to thromboembolic events in the perioperative and postoperative periods, even with minor surgeries.

• #5 Homocystinuria diagnosis and management: it is not all classical | Journal of Clinical Pathology

  https://jcp.bmj.com/content/75/11/744

  Learning disabilities are not universal or may be subtle and, when present, include global intellectual impairment, specific learning disabilities such as autism and behavioural disturbance. […] The primary goal is to maintain plasma tHCy concentration at less than 100 mol/L in adults and less than 50 mol/L in children at which thromboembolic risk is reversed, lens subluxation is halted and bone growth in children proceeds normally. […] Very early initiation of treatment allows for normal intellectual development, but once learning difficulties are evident they are not reversed by treatment. […] In classical HCU, remethylation is the only route available for HCy metabolism, and consequently, methionine is high and cystine, distal to the defective CBS enzyme, is low. Conversely, in remethylation disorders, CBS is the only route available for HCy metabolism, therefore, methionine is low.

• #5 Betaine anhydrous in homocystinuria: results from the RoCH registry | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-019-1036-2

  Homocystinuria is an autosomal recessive disorder of homocysteine metabolism leading to increased plasma, urine and tissue accumulation of homocysteine and its metabolites. The clinical manifestations of classical homocystinuria include skeletal abnormalities, osteoporosis, ectopia lentis and/or severe myopia, cognitive impairment, developmental delay/intellectual disability, seizures, psychiatric disorders, atherosclerosis and thromboembolism. If untreated, homocystinuria is a serious, life-threatening disease. […] A broad range of clinical presentations associated with homocystinuria were observed during the study period. CBS-deficient vitamin B6 non-responders mainly reported ocular (74.0%), skeletal (72.0%), neurologic (66.0%) and cardiovascular (46.0%) symptoms. Skeletal and cardiovascular issues were reported by 77.8% of CBS-deficient B6 responders, followed by ocular (66.7%) and neurologic (55.6%) abnormalities. The majority of Cbl metabolism-defective patients (80.0%) reported neurologic disorders, followed by ocular and hematologic disorders in 66.7 and 64.4% of patients, respectively. All MTHFR-deficient patients had neurologic impairment, over half (52.4%) had psychiatric disturbances, and skeletal disorders were reported in 38.1% of these patients.

• #5 Methylmalonic acidemia with homocystinuria: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/methylmalonic-acidemia-with-homocystinuria/

  Methylmalonic acidemia with homocystinuria is a disorder in which the body is unable to correctly process certain protein building blocks (amino acids), fat building blocks (fatty acids), and cholesterol. The signs and symptoms of methylmalonic acidemia with homocystinuria usually develop in infancy, although they can begin at any age. When the condition begins early in life, affected individuals typically grow more slowly than expected. These infants can also have difficulty feeding and have an abnormally pale appearance (pallor). Eye abnormalities and neurological problems, including weak muscle tone (hypotonia) and seizures, are also common in people with methylmalonic acidemia with homocystinuria. Many infants and children with this condition have delayed development and intellectual disability, and some have an unusually small head size (microcephaly).

• #5 WV DHHR – OMCFH – Newborn Metabolic Screening – Homocystinuria

  https://www.wvdhhr.org/nbms/diseases/Homocystinuria.asp

  The potential for early clinical diagnosis is limited. Ocular abnormalities, because of their distinctive lens displacement, may lead to the diagnosis. The diagnosis should be considered in any child or young adult with thromboembolism affecting both the large and small arteries as well as the veins, particularly in association with developmental disabilities, mental retardation, or skeletal findings. Most patients, however, have nonspecific features so that definitive testing involving the measurement of serum or urine amino acids is not accomplished before the expression of more severe clinical symptoms. Treatment seems to reduce the risk of thromboembolic episodes. Because this is the major cause of mortality and morbidity in these patients, the survival rate may improve with early, effective treatment. The incidence of mental retardation may be prevented or reduced. For patients with classic (homozygous) homocystinuria, early treatment with good biochemical control (lifetime plasma-free homocystine 11 mol/L) seems to prevent mental retardation, ectopia lentis seems to be delayed, and the incidence of seizures is reduced.

• #5 What is Homocystinuria (HCU)? – Nutricia Metabolics

  https://www.nutriciametabolics.com/hcu/

  An important aspect of management is frequent monitoring to make sure diet, formula prescription and medication dose are appropriate. Monitoring typically includes blood tests; amino acid levels are checked often, and folate and vitamin B12 levels may be checked as well. In addition, follow-up includes monitoring of complications associated with HCU; this may include eye exams, other blood tests, and imaging studies.

• #6 Homocystinuria – Wikipedia

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

  Homocystinuria (HCU) is an inherited disorder of the metabolism of the amino acid methionine due to a deficiency of cystathionine beta synthase or methionine synthase. Symptoms of homocystinuria can also be caused by a deficiency of vitamins B6, B12, or folate. […] This defect leads to a multi-systemic disorder of the connective tissue, muscles, central nervous system (CNS), and cardiovascular system. Homocystinuria represents a group of hereditary metabolic disorders characterized by an accumulation of the amino acid homocysteine in the serum and an increased excretion of homocysteine in the urine. Infants appear to be normal and early symptoms, if any are present, are vague. […] Signs and symptoms of homocystinuria that may be seen include the following: A family history of homocystinuria, Flush across the cheeks, Tall, thin build resembling Marfanoid habitus, Long limbs (dolichostenomelia), High-arched feet (pes cavus), Knock knees (genu valgum), Pectus excavatum and Pectus carinatum, Intellectual disability, Seizures, Psychiatric disease, Eye anomalies, Vascular disease. […] The life expectancy of patients with homocystinuria is reduced only if untreated. It is known that before the age of 30, almost one quarter of patients die as a result of thrombotic complications (e.g., heart attack).

• #6 Homocystinuria (HCU): Symptoms, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/25160-homocystinuria

  Homocystinuria symptoms may include: […] The symptoms of the most common type of homocystinuria usually involve your: […] Eyes. […] Dislocation of the lenses of your eyes (ectopia lentis). […] Severe nearsightedness (myopia). […] Skeletal system. […] Excessive growth. […] Long arms, legs, fingers and toes. […] Knees bent inward that touch when legs are straight (knock knees). […] Sunken or protruding chest. […] Curvature of your spine (scoliosis). […] People with homocystinuria are also at risk of developing early osteoporosis. […] Central nervous system. […] Developmental delays. […] Learning problems. […] Vascular system. […] Increased risk of blood clots, which can lead to stroke or pulmonary embolism. […] The symptoms of homocystinuria vary based on which type you have. They typically develop during the first few years of life. But some people dont develop any symptoms until adulthood. […] With early diagnosis and lifelong treatment, most children with homocystinuria can expect to live normal, healthy lives.

• #6

  http://www.ncbi.nlm.nih.gov/medgen/199606

  Classic homocystinuria is an autosomal recessive metabolic disorder of sulfur metabolism. The clinical features of untreated homocystinuria due to CBS deficiency usually manifest in the first or second decade of life and include myopia, ectopia lentis, mental retardation, skeletal anomalies resembling Marfan syndrome (MFS; 154700), and thromboembolic events. […] Thromboembolism is the major cause of early death and morbidity. IQ in individuals with untreated homocystinuria ranges widely, from 10 to 138. In B6-responsive individuals the mean IQ is 79 versus 57 for those who are B6-non-responsive. Other features that may occur include: seizures, psychiatric problems, extrapyramidal signs (e.g., dystonia), hypopigmentation of the skin and hair, malar flush, livedo reticularis, and pancreatitis.

• #6 Homocystinuria

  https://dermnetnz.org/topics/homocystinuria

  Newborns with homocystinuria often appear normal, but signs and symptoms begin to develop in the first year of life, though they are not all obvious at first. […] Signs and symptoms of homocystinuria may vary widely, and patients can present with any of the following: Marfanoid appearance (this refers to the tall, thin build and long-limbed appearance reminiscent of Marfan syndrome), Pectus carinatum or pectus excavatum (the depression of protrusion of the sternum), High, arched palate with crowding of the teeth, Kyphoscoliosis, Ectopic lentis (dislocation of the lens), Myopia, Glaucoma, Intellectual disability (with an average IQ of 80, although approximately 30% of patients with homocystinuria have IQs in the normal range), Arachnodactyly (long, spidery fingers), Seizures, Cerebrovascular events, Psychiatric disorders, Osteoporosis, Infant failure to thrive, Increased chance of blood clot formation and for deep vein thrombosis. […] Many patients with homocystinuria die as young adults due to arterial and venous thrombosis.

• #6 Homocystinuria (HCY) | New York State Department of Health, Wadsworth Center

  https://www.wadsworth.org/public-health-programs/newborn-screening/newborn-screening-program/homocystinuria-hcy

  There are two types of homocystinuria: vitamin B6 responsive and non-vitamin B6 responsive. The symptoms of vitamin B6 responsive homocystinuria are usually milder. The symptoms of untreated homocystinuria vary from one person to the next, but may include developmental delay, near sightedness (myopia), skeletal abnormalities (long limbs) and increased risk of blood clots (thromboembolism). […] Intellectual disability is usually more severe in untreated non-vitamin B6 responsive homocystinuria. […] On treatment, prognosis is significantly improved.

• #6 Newborn screening information for Methylmalonic aciduria with homocystinuria | Baby’s First Test | Newborn Screening | Baby Health

  https://www.babysfirsttest.org/newborn-screening/conditions/methylmalonic-acidemia-with-homocystinuria

  Signs of methylmalonic acidemia with homocystinuria (Cbl C, D, F) could begin anywhere between the first few days of life and 14 years of age. Children with Cbl C usually show symptoms between the first few days and the first month of life. Children with Cbl D deficiency do not show signs until later in childhood. […] If your baby has Cbl C, D, F, you might notice signs including: Delayed growth, Small head size, Skin rash, Vomiting, Poor appetite, Diarrhea, Fever, Sleeping longer or more often, Tiredness, Weak muscle tone (called hypotonia). […] Many of these signs may occur when your baby eats foods that their body cannot break down. They can be triggered by long periods of time without eating, illnesses, and infections. […] Since methylmalonic acidemia with homocystinuria (Cbl C, D, F) is rare, it is not yet certain how effective these dietary and supplement treatments are. It has been recognized that treatments helped some children avoid the signs and symptoms of the condition, whereas they did not help other children. […] It is possible for children with the condition to have learning disabilities, intellectual disabilities, or other complications, even with treatment.

• #7 Homocystinuria – UF Health

  https://ufhealth.org/conditions-and-treatments/homocystinuria

  Newborn infants appear healthy. Early symptoms, if present, are not obvious. […] Symptoms may occur as mildly delayed development or failure to thrive. Increasing visual problems may lead to diagnosis of this condition. […] Other symptoms include: Chest deformities (pectus carinatum, pectus excavatum), Flush across the cheeks, High arches of the feet, Intellectual disability, Knock knees, Long limbs, Mental disorders, Nearsightedness, Spidery fingers (arachnodactyly), Tall, thin build. […] Although no cure exists for homocystinuria, vitamin B therapy can help about half of people affected by the condition. […] If the diagnosis is made in childhood, starting a low-methionine diet quickly may prevent some intellectual disability and other complications of the disease. […] Intellectual disability is a serious outcome of the disease. But, it can be reduced if diagnosed early.

• #7 Homocystinuria diagnosis and management: it is not all classical | Journal of Clinical Pathology

  https://jcp.bmj.com/content/75/11/744

  Homocystinuria (HCU) refers to a group of inherited disorders of homocysteine metabolism associated with high blood homocysteine concentration, thromboembolic tendency and neurocognitive symptoms. […] Thromboembolic tendency increases in direct proportion to the magnitude and duration of HCy elevation. Left untreated there’s a 30% chance of a vascular event by age 20 rising to 50% by the age of 30. […] Lens subluxation is a hallmark of HCU distinguishing it from remethylation disorders and is detectable in approximately 70% of untreated patients by the age of 10 and in over 90% diagnosed later. […] Skeletal and connective tissue disorders affect approximately 50% of HCU patients, and may variably include elongated long bones (Marfanoid body habitus), arachnodactyly, joint laxity, osteopenia, scoliosis and vertebral collapse.

• #7 Current and Novel Therapeutical Approaches of Classical Homocystinuria in Childhood With Special Focus on Enzyme Replacement Therapy, Liver-Directed Therapy and Gene Therapy | Bittmann | Journal of Clinical Medicine Research

  https://www.jocmr.org/index.php/JOCMR/article/view/4843/25893677

  Overall, the disease is a defect in methionine metabolism. […] Cystathionine beta deficiency presents with many different symptoms and pathological features, particularly affecting the eye, skeleton deformities, central nervous system (CNS) disturbances and vascular diseases. At birth, the children are still normal. If untreated, the disease is progressive. Symptoms in the eyes, an ocular hallmark, include ectopia lentis (50% of cases) with disruption of zonular fasers and high-grade myopia. Skeletal symptoms include genu valgum, dolichostenomelia, moreover pectus excavatum or carinatum, and osteoporosis. The most prominent cause of morbidity and mortality is thromboembolism of the great and small arteries and veins. Decreased intelligence rarely becomes manifest in the first or second year of life. Clinically significant psychiatric problems are present in 50% of patients. However, other organs, including the liver, hair, and skin, also show symptoms of the disease.

• #7 Methylmalonic acidemia with homocystinuria: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/methylmalonic-acidemia-with-homocystinuria/

  Some people with methylmalonic acidemia with homocystinuria develop a blood disorder called megaloblastic anemia. The signs and symptoms of early-onset methylmalonic acidemia with homocystinuria worsen over time, and the condition can be life-threatening if it is not treated. […] When methylmalonic acidemia with homocystinuria begins in adolescence or adulthood, it may change an affected person’s behavior and personality; the person may become less social and may experience hallucinations, delirium, and psychosis. In addition, these individuals can begin to lose previously acquired mental and physical abilities, resulting in a decline in school or work performance, difficulty controlling movements, memory problems, speech difficulties, a decline in intellectual function (dementia), or an extreme lack of energy (lethargy). Some people with methylmalonic acidemia with homocystinuria whose signs and symptoms begin later in life develop a condition called subacute combined degeneration of the spinal cord, which leads to numbness and weakness in the lower limbs, difficulty walking, and frequent falls.

• #8 Homocystinuria (HCU): Symptoms, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/25160-homocystinuria

  Homocystinuria symptoms may include: […] The symptoms of the most common type of homocystinuria usually involve your: […] Eyes. […] Dislocation of the lenses of your eyes (ectopia lentis). […] Severe nearsightedness (myopia). […] Skeletal system. […] Excessive growth. […] Long arms, legs, fingers and toes. […] Knees bent inward that touch when legs are straight (knock knees). […] Sunken or protruding chest. […] Curvature of your spine (scoliosis). […] People with homocystinuria are also at risk of developing early osteoporosis. […] Central nervous system. […] Developmental delays. […] Learning problems. […] Vascular system. […] Increased risk of blood clots, which can lead to stroke or pulmonary embolism. […] The symptoms of homocystinuria vary based on which type you have. They typically develop during the first few years of life. But some people dont develop any symptoms until adulthood. […] With early diagnosis and lifelong treatment, most children with homocystinuria can expect to live normal, healthy lives.

• #8 WV DHHR – OMCFH – Newborn Metabolic Screening – Homocystinuria

  https://www.wvdhhr.org/nbms/diseases/Homocystinuria.asp

  The potential for early clinical diagnosis is limited. Ocular abnormalities, because of their distinctive lens displacement, may lead to the diagnosis. The diagnosis should be considered in any child or young adult with thromboembolism affecting both the large and small arteries as well as the veins, particularly in association with developmental disabilities, mental retardation, or skeletal findings. Most patients, however, have nonspecific features so that definitive testing involving the measurement of serum or urine amino acids is not accomplished before the expression of more severe clinical symptoms. Treatment seems to reduce the risk of thromboembolic episodes. Because this is the major cause of mortality and morbidity in these patients, the survival rate may improve with early, effective treatment. The incidence of mental retardation may be prevented or reduced. For patients with classic (homozygous) homocystinuria, early treatment with good biochemical control (lifetime plasma-free homocystine 11 mol/L) seems to prevent mental retardation, ectopia lentis seems to be delayed, and the incidence of seizures is reduced.

• #8 What Is Homocystinuria?

  https://www.webmd.com/children/what-is-homocystinuria

  Babies born with homocystinuria look perfectly fine. Signs and symptoms start to show up within the first few years of life. […] HCY affects all kids differently. If your child has it, they may have many or none of these symptoms: Pale hair and skin, Abnormally-shaped chest, Slow weight gain and growth, Severe nearsightedness and lens dislocation (which can lead to blindness), Tall, slender build, Long, skinny fingers, Weak bones, Blood clots (increasing the risk for stroke and heart disease), Seizures. […] Other symptoms may include: Developmental delays (slow to crawl, walk, and talk), Learning disabilities and intellectual issues, Behavior and emotional problems. […] If your child begins treatment as a baby and stays on it, theyll probably grow and develop normally. Treatment also can lower the risk of strokes, heart disease, and blood clots. Vision problems may still happen even with treatment. These can be fixed with surgery or other methods.

• #8 Methylmalonic acidemia with homocystinuria: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/methylmalonic-acidemia-with-homocystinuria/

  Some people with methylmalonic acidemia with homocystinuria develop a blood disorder called megaloblastic anemia. The signs and symptoms of early-onset methylmalonic acidemia with homocystinuria worsen over time, and the condition can be life-threatening if it is not treated. […] When methylmalonic acidemia with homocystinuria begins in adolescence or adulthood, it may change an affected person’s behavior and personality; the person may become less social and may experience hallucinations, delirium, and psychosis. In addition, these individuals can begin to lose previously acquired mental and physical abilities, resulting in a decline in school or work performance, difficulty controlling movements, memory problems, speech difficulties, a decline in intellectual function (dementia), or an extreme lack of energy (lethargy). Some people with methylmalonic acidemia with homocystinuria whose signs and symptoms begin later in life develop a condition called subacute combined degeneration of the spinal cord, which leads to numbness and weakness in the lower limbs, difficulty walking, and frequent falls.

• #9 Homocystinuria diagnosis and management: it is not all classical | Journal of Clinical Pathology

  https://jcp.bmj.com/content/75/11/744

  Homocystinuria (HCU) refers to a group of inherited disorders of homocysteine metabolism associated with high blood homocysteine concentration, thromboembolic tendency and neurocognitive symptoms. […] Thromboembolic tendency increases in direct proportion to the magnitude and duration of HCy elevation. Left untreated there’s a 30% chance of a vascular event by age 20 rising to 50% by the age of 30. […] Lens subluxation is a hallmark of HCU distinguishing it from remethylation disorders and is detectable in approximately 70% of untreated patients by the age of 10 and in over 90% diagnosed later. […] Skeletal and connective tissue disorders affect approximately 50% of HCU patients, and may variably include elongated long bones (Marfanoid body habitus), arachnodactyly, joint laxity, osteopenia, scoliosis and vertebral collapse.

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