Materiały źródłowe

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

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

  Homocystinuria is a genetic disorder that causes a buildup of homocysteine in your blood and urine. […] With homocystinuria, your body lacks an enzyme that it needs to metabolize homocysteine properly and keep it within a normal range. […] Genetic changes (mutations) in many different genes cause most types of homocystinuria. A mutation in the CBS gene causes the most common type of homocystinuria. […] Mutations in the MTHFR, MTR, MTRR and MMADHC genes can also cause homocystinuria. […] Homocystinuria can also occur due to non-genetic reasons. A severe lack of vitamin B6, vitamin B9 (folate) or vitamin B12 may cause the condition.

• #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). […] Classic homocystinuria is caused by deficiency of cystathionine -synthase (CBS), a pyridoxine (vitamin B6)-dependent enzyme. […] Homocystinuria is inherited in an autosomal recessive manner. […] The two phenotypic variants of classic homocystinuria are B6-responsive and B6-non-responsive homocystinuria. B6-responsive homocystinuria is typically (but not always) milder than the non-responsive variant. […] „Homocystinuria” was named for excess homocystine in the urine, though now it is primarily detected by increased total homocysteine in plasma. Homocystinuria may be caused by genetically determined deficient activity of cystathionine -synthase (CBS), or a variety of genetic problems that ultimately interfere with conversion of homocysteine to methionine. […] Non-genetically determined severe dietary lack of cobalamin (vitamin B12 deficiency) may also cause „homocystinuria”.

• #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/

  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. […] Homocystinuria due to MTHFR deficiency (OMIM ID: 236250) was first described in 1972 by Mudd et al. in a 16-year-old boy with muscle weakness, seizures and abnormal encephalographic signs, a 17-year-old girl with mental degradation and schizophrenia and her sister. […] Severe MTHFR deficiency is biochemically characterized by hyperhomocysteinemia, homocystinuria, increased cystathionine, and low or low-normal Met, in contrast with CBS deficiency, which presents with elevated Met. […] 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: Causes, Symptoms & Diagnosis

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

  Homocystinuria is an inherited disorder that keeps the body from processing the essential amino acid methionine. […] Certain genetic mutations present at birth cause this disease. More than 150 mutations that cause homocystinuria have been found in the gene cystathionine beta-synthase, which is also known as the CBS gene. […] In rare cases, mutations in other genes like MTHFR, MTR, or MTRR cause the disorder. Homocystinuria is an autosomal recessive trait. This means that for a child to have the signs or symptoms of this condition, they would need to inherit the mutated gene from both parents.

• #1 Methylmalonic acidemia with homocystinuria: MedlinePlus GeneticsLock

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

  Methylmalonic acidemia with homocystinuria can be caused by variants (also known as mutations) in one of several genes, including MMACHC, MMADHC, LMBRD1, and ABCD4. Variants in these genes account for the different types of the disorder: cblC, cblD, cblF, and cblJ, respectively. Another type, called epi-cblC, is caused by variants in the PRDX1 gene, usually in combination with an MMACHC gene variant. […] Variants in the HCFC1 gene are the most common cause of a condition called methylmalonic acidemia with homocystinuria, cblX type. This gene provides instructions for making a protein that helps regulate the activity of other genes, including the MMACHC gene. Variants in the HCFC1 gene (and, less commonly, other related genes) likely disrupt the normal activity of the MMACHC gene, impairing vitamin B12 processing and leading to methylmalonic acidemia or homocystinuria. […] Variants in other genes involved in vitamin B12 processing can cause related conditions. Variants that impair only AdoCbl production lead to methylmalonic acidemia, and variants that impair only MeCbl production cause homocystinuria.

• #1 Homocystinuria

  https://www.nhs.uk/conditions/homocystinuria/

  Homocystinuria (HCU) is a rare but potentially serious inherited condition. […] The genetic cause (mutation) responsible for HCU is passed on by parents, who usually don’t have any symptoms of the condition. […] The way this mutation is passed on is known as autosomal recessive inheritance. This means a baby needs to receive two copies of the mutated gene to develop the condition one from their mother and one from their father. […] Although it’s not possible to prevent HCU, it’s important to let your midwife and doctor know if you have a family history of the condition.

• #1 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. […] The main and most prevalent cause of acquired homocystinuria involves enzyme and cofactor dysfunctions involving defects in remethylation and transsulfuration. […] Non-genetic hyperhomocysteinemia can be caused by lifestyle factors like cigarette smoking, alcohol consumption, and coffee consumption in addition to medications like methotrexate, nitrous oxide, phenytoin, and carbamazepine. […] Hyperhomocysteinemia is also positively associated with congestive heart failure, serving as a prognostic marker for long-term cardiac events, but there still lacks a clear disease mechanism.

• #1 Methionine Metabolism Disorders – Pediatrics – Merck Manual Professional Edition

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

  Homocysteine is an intermediate in methionine metabolism; it is either remethylated to regenerate methionine or combined with serine in a series of transsulfuration reactions to form cystathionine and then cysteine. […] Various defects in remethylation or transsulfuration can cause homocysteine to accumulate, resulting in disease. […] This disorder is caused by an autosomal recessive deficiency of cystathionine beta-synthase, which catalyzes cystathionine formation from homocysteine and serine. […] Homocysteine accumulates and dimerizes to form the disulfide homocystine, which is excreted in the urine. […] Because remethylation is intact, some of the additional homocysteine is converted to methionine, which accumulates in the blood. […] Excess homocysteine predisposes to thrombosis and has adverse effects on connective tissue (perhaps involving fibrillin), particularly the eyes and skeleton; adverse neurologic effects may be due to thrombosis or a direct effect.

• #1 Homocystinuria

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

  Homocystinuria, or accumulation of homocysteine in the blood and urine, is due to an inborn error in methionine metabolism that is commonly inherited in an autosomal recessive fashion. The prevalence of all types of homocystinuria is estimated to be 1: 344,000. There are different types of homocystinuria with the most common type caused by a deficiency in the enzyme cystathionine beta-synthase, which occurs in about 1:50,000 births. This type of homocystinuria is usually detected on newborn screening tests. […] To better describe the pathophysiology of homocystinuria, it is separated into three major categories based on the site of the metabolic defect. Type 1 is due to a deficiency in cystathionine beta-synthase, which converts homocysteine to cystathionine. Type 2 is due to defective methylcobalamin synthesis, which helps to convert homocysteine to methionine. Type 3 is due to an abnormality in methylene tetrahydrofolate reductase, which also helps to convert homocysteine to methionine.

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

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

  In addition to genetic etiologies, homocystinuria can also be caused by acquired forms of secondary to severe cobalamin (B12) deficiency. […] Homocystinuria is an autosomal recessive inherited disorder due to deficiency of cystathionine beta-synthase (EC 4.2.1.22, McKusick 236200). […] More than 320 individual homocystinuric alleles have been studied, and 100 mutations were detected. […] Deficiency of cystathionine beta-synthase leads to tissue accumulation of methionine, homocysteine, and their S-adenosyl derivatives, with lack of cystathionine and low levels of cysteine. […] The pathophysiology of cystathionine beta-synthase deficiency has not yet been completely elucidated, but accumulation of homocysteine probably plays a major role in determining some of the most relevant clinical manifestations, including generalized vascular damage and thromboembolic complications.

• #1

  https://www.omim.org/entry/236200

  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. […] Caused by mutation in the cystathionine beta-synthase gene (CBS, 613381.0001).

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

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

  A rare metabolic disease of methionine catabolism characterized by accumulation of methionine and homocysteine with clinical involvement of the eye, skeletal system, vascular system and central nervous system (CNS). […] The disease is caused by mutations in the CBS gene (21q22.3) leading to the accumulation of homocysteine and methionine, which are toxic for the endothelium, and causes neurocognitive impairment. […] Cysteine deficiency probably plays a role in connective tissue abnormalities, including lens dislocation.

• #1

  https://www.omim.org/entry/236200

  A number sign (#) is used with this entry because homocystinuria with or without response to pyridoxine is caused by homozygous or compound heterozygous mutation in the gene encoding cystathionine beta-synthase (CBS; 613381) on chromosome 21q22. […] 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. […] There are 2 main phenotypes of the classic disorder: a milder pyridoxine (vitamin B6)-responsive form, and a more severe pyridoxine-nonresponsive form. […] 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.

• #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/

  This paper reviews the clinical and biochemical findings and management of the three most frequent genetic causes of homocystinurias: CBS deficiency or classical homocystinuria (HCU), methylmalonic aciduria with homocystinuria cblC type, and severe MTHFR deficiency. […] These three disorders all present with severe hyperhomocysteinemia, while Met levels are increased in HCU and decreased or normal in cblC and MTHFR deficiency, and methylmalonic acid (MMA) is increased only in cblC. […] In CBS deficient patients at diagnosis folate is often deficient likely due to the inhibition of MTHFR resulting in decreases of 5MTHF, the circulation form of folate. […] In MTHFR deficiency folate is severely deficient, whereas in cblC defect all folates accumulate as 5MTHF resulting in functional cellular folate deficiency.

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

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

  The term „homocystinuria” designates a biochemical abnormality, not a specific disease entity. There are many causes of homocystinuria. All affect one of the transsulfation pathways that convert the sulfur atom of methionine into the sulfur atom of cysteine. This pathway is the chief route of disposal of methionine. The most common defect, cystathionine -synthase (CBS) deficiency (OMIM database No. 236200), results in high concentrations of serum methionine. One form of CBS deficiency is responsive to vitamin B6. Other metabolic variants of homocystinuria include defects of vitamin B12 uptake or activation and tetrahydrofolate reductase deficiency (OMIM database No. 236250). […] More than 90 different disease-associated mutations of the CBS gene have been identified. The vast majority of these mutations are „private” mutations that occur in only a single or a very small number of families. The most prevalent mutations are the G307S and I278T mutations. Affected patients vary widely in the extent to which they manifest clinical abnormalities, suggesting considerable genetic heterogeneity. Some of the variability is accounted for by the relative reduction of enzymatic activity. Absent to relatively low residual activity (up to 10%) of CBS has been noted among different families. However, there are reports of individuals with the identical genotype resulting in a different phenotype within the same family.

• #1 Homocystinuria | PPT

  https://www.slideshare.net/slideshow/homocystinuria-238455286/238455286

  Homocystinuria is a disorder of methionine metabolism, leading to an abnormal accumulation of homocysteine and its metabolites (homocystine, homocysteine-cysteine complex) in blood and urine. […] Homocystinuria is inherited as an autosomal recessive trait. Prevalence of 1 in 200,000 to 350,000 live births has been estimated. […] Homocystinuria Caused by Cystathionine -Synthase Deficiency (Classic Homocystinuria) Methionine is an essential, non-polar -amino acid. Under normal conditions methionine undergoes conversion to homocysteine. […] People suffering from this disease are unable to synthesize CBS, hence leading to an inability to metabolize methionine Due to the absence of CBS enzyme, homocysteine accumulates in the blood serum leading to an increased excretion of homocystine in the urine.

• #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

  The drug, betaine, can also help to lower homocysteine concentrations. […] Currently, newborn screening programmes targeting at least one of the homocystinurias (most frequently CBS deficiency) are in place in several European countries such as the Czech Republic, Germany, Spain, the UK and Ireland; in several US states; in Qatar, Japan, Korea; and in Australia. […] 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. […] Long diagnostic delays have been found in previous series and the delay has sometimes correlated with age. […] Newborn screening is well suited to treatable diseases whose clinical diagnosis is often delayed. […] Approximately one quarter of the patients in this survey had been detected by newborn screening and reported higher satisfaction with the diagnostic procedure and with treatment and medical care than those detected clinically.

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

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

  In a minority of cases serum B12 and folate results may not reflect whole body deficits and if deficiency is suspected, confirmatory tests are indicated. […] Once secondary causes are excluded, measurement of other amino acids in the HCy metabolic pathway, notably methionine and cystine, with quantitation of MMA in plasma or urine helps to distinguish between the genetic conditions of classical HCU and remethylation defects caused by MTHF reductase (MTHFR) or a disorder of cobalamin metabolism. […] HCU caused by CBS deficiency is the most common condition of hyperhomocystinaemia. […] Thromboembolic tendency increases in direct proportion to the magnitude and duration of HCy elevation. […] The CBS enzyme uses pyridoxal 5-phosphate as a cofactor. Approximately 50% of patients with HCU respond partially or wholly to high-dose pyridoxine (vitamin B6).

• #1 Homocystinuria | Amino Acid Metabolism Disorder – Causes, Symptoms, Diagnosis and Treatment

  https://www.medindia.net/health/conditions/homocystinuria-amino-acid-metabolism-disorder.htm

  When CBS is deficient, homocysteine accumulates in the tissues along with its precursor amino acid methionine. […] High levels of homocysteine mainly affect supporting connective tissue in different parts of the body. […] The build-up of homocysteine also damages the supporting tissue of the body’s skeleton, and damages the connective tissue in the walls of blood vessels. […] Diagnosis is suspected during clinical examination and based on clinical suspicion diagnosis is confirmed by blood tests, imaging tests and skin biopsy. […] Genetic testing can be done to look for presence of the abnormal gene. […] It is difficult to prevent homocystinuria as this disorder occurs due to genetic mutations. […] Complications of homocystinuria may be prevented by screening of newborns with a blood test around five days within birth to check for the condition so that early treatment can be started.

• #1 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. […] Variants (also called mutations) in the CBS, MTHFR, MTR, MTRR, and MMADHC genes cause homocystinuria. […] Variants in the CBS gene cause classic homocystinuria. […] Rarely, homocystinuria can be caused by variants in several other genes. […] Researchers have not determined how excess homocysteine and related compounds lead to the signs and symptoms of homocystinuria.

• #1 Homocystinuria – EyeWiki

  https://eyewiki.org/Homocystinuria

  High blood homocysteine level can also provoke Alzheimers disease and acts as a modifiable risk factor for cognitive dysfunction. […] The precise mechanisms for hyperhomocysteinemia related eye disease remain ill defined. […] The primary goal of systemic management is to maintain appropriate levels of homocysteine and to prevent thrombosis. […] Several new therapies are emerging for homocystinuria, including strategies to reduce the amount of methionine absorbed from food, so patients dont have to focus as hard to eat a methionine-restricted diet.

• #1 Homocystinuria

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

  In this discussion, we will focus on homocystinuria due to methionine synthase deficiency, which is a defect in the methylation pathway of homocysteine. This specific deficiency is characterized by homocystinuria, hyperhomocysteinemia, and hypomethioninemia, without methylmalonic aciduria. Methionine synthase catalyzes the methylation of homocysteine to methionine and can be caused by deficiency in methylene tetrahydrofolate reductase or by deficiency of methylcobalamin cofactors. The patient in this case possesses the cb1G defect, or cobalamin G deficiency, leading to a deficiency in methylcobalamin cofactors. […] There have been few studies that offer theories for the pathophysiologic mechanisms underlying the ocular sequelae of homocystinuria. Poloschek et al. investigated ERG findings in those with methionine synthase deficiency and proposed that increased homocysteine levels decrease the transport of folates to photoreceptors, which in turn decrease intracellular anabolic processes, impacting cone photoreceptor function. They also commented that hyperhomocysteinemia may lead to microvascular damage in the retina, leading to reduced oscillatory potentials. It may also have toxic effects on the neurons of the ganglion cell layer, leading to deformed flash visual evoked potential (VEP) responses.

• #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/abstract/?lang=en

  Genetic homocystinurias are a group of inborn errors of metabolism that result in the massive excretion of homocysteine (Hcy) in the urine due to Hcy accumulation in the body, usually causing neurological and cardiovascular complications. The three most frequent causes are classical homocystinuria [deficiency of cystathionine beta-synthase (CBS)], methylmalonic aciduria with homocystinuria, cblC type (cblC deficiency) and severe methylenetetrahydrofolate reductase (MTHFR) deficiency. […] Moreover, patients with remethylation defects typically do not present ectopia lentis and bone disturbances, tall stature and osteoporosis. […] Whereas hematological alterations, such as megaloblastic anemia, thrombocytopenia neutropenia and life-threatening microangiopathy, are specific findings of cblC deficiency.

• #1 Influence of Metabolic Control on Growth in Homocystinuria due to Cystathionine B-Synthase Deficiency | Pediatric Research

  https://www.nature.com/articles/pr2001129

  The etiology of the tall stature almost invariably seen in homocystinuric patients is not known. […] It has been difficult to relate this wide variety of symptoms to a deficiency of a single enzyme. […] Both HC and HCA, the sulfonic acid derivative of HC, have been suggested as the cause of the excessive growth. […] These findings have been challenged by other studies that have implicated HC as the agent responsible for growth. […] The cause of the tall stature in homocystinuric patients is controversial. […] An association between increased growth and HC was found in the present study. […] The differences in growth between these two groups of patients cannot be attributed to nutritional factors. […] This suggests that growth is affected only when the HC is greatly increased and, thus, supports the findings of this report. […] A direct effect of HC on cell proliferation has been demonstrated in several studies. […] The present study demonstrates a direct effect of HC on human growth; the exact mode of its action still needs to be determined.

• #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. […] The most prevalent inherited disorder of homocysteine metabolism is classical HCU caused by deficiency of the pyridoxine-dependent enzyme, cystathione beta-synthase, which converts homocysteine to cystathionine in the transsulphuration pathway. […] Primary genetic disorders affecting function of CBS (classical HCU) or enzymes involved in remethylation impair metabolism of HCy causing it to rise in plasma from a reference concentration below 15 mol/L to at least 40 mol/L and usually over 100 mol/L. […] The most common causes of a high tHCy relate to underlying vitamin B12 or folate deficiency which is often first suspected when the CBC reveals a macrocytic anaemia.

• #1 CBS (homocystinemia/cystathionine beta-synthase deficiency) – newbornscreening.info

  https://www.newbornscreening.info/cbs-homocystinemia-cystathionine-beta-synthase-deficiency/

  When both parents are carriers, there is a 25% chance in each pregnancy for the child to have homocystinuria. […] About one in every 200,000 to 300,000 babies in the United States is born with homocystinuria. […] This condition occurs in all ethnic groups around the world. It is found more often in white people from the New England region of the United States. It is also more common in people with Irish ancestry.

• #1 Homocystinuria: Causes, symptoms, and tests

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

  Homocystinuria is a genetic disorder in which the body cannot break down a particular amino acid. […] The disorder passes from parents to children in an autosomal recessive manner, which means that two copies of an irregular gene must be present for it to develop. […] As homocystinuria is genetically autosomal recessive, a child must inherit a copy of the mutated gene for homocystinuria from each parent to develop the condition. […] Parents who carry just one mutated gene may not have any symptoms of homocystinuria. […] According to researchers, the child of parents who both are carriers of the gene has a 25% chance of having homocystinuria. […] The most common form of homocystinuria is called cystathionine beta-synthase (CBS). […] There is no cure for homocystinuria. However, it is possible to manage the condition with dietary restrictions, supplements, and medication. […] The only reason for genetic testing is to give people an idea of their risk of passing on a gene mutation that can lead to homocystinuria.

• #1 Homocystinuria – Child Neurology Foundation

  https://www.childneurologyfoundation.org/disorder/homocystinuria/

  There are other nongenetic causes of high homocysteine in the blood and urine. These causes are more common than genetic causes. They can have different signs and symptoms. Nongenetic causes can include: […] Vitamin deficiencies, particularly Vitamin B6 or Vitamin B12 deficiencies […] Low thyroid hormone levels […] Diabetes […] High cholesterol […] High blood pressure […] Medications, such as carbamazepine, phenytoin, atorvastatin, methotrexate […] Smoking […] Advanced age.

• #1 Homocystinuria: pathogenetic mechanisms – PubMed

  https://pubmed.ncbi.nlm.nih.gov/324277/

  Homocystinuria with elevated plasma homocysteine and methionine levels is the result of deficient activity of cystathionine synthetase, the enzyme catalyzing conversion of homocysteine to cystathionine. […] It is inherited as an autosomal recessive trait with a worldwide distribution. […] Low methionine homocystinuria, with deficient remethylation of homocysteine, results from deranged vitamin B(12) metabolism and from deficient 5,10-methylene-tetrahydrofolate reductase. […] Administration of azaribine produces homocystinuria by mechanism not yet elucidated.

• #1 Homocystinuria | Amino Acid Metabolism Disorder – Causes, Symptoms, Diagnosis and Treatment

  https://www.medindia.net/health/conditions/homocystinuria-amino-acid-metabolism-disorder.htm

  Homocystinuria is a rare inherited genetic disorder. […] When the term homocystinuria is used, it normally refers to classical homocystinuria caused by deficiency of the enzyme cystathionine beta synthase (CBS). […] The defect has been mapped to a gene on chromosome 21. […] In addition to CBS deficiency, there are six other distinct types of homocystinuria due to other enzyme deficiencies including 5,10-methylenetetrahydrofolate reductase deficiency and deficiency of cobalamin in coenzyme synthesis. […] These other deficiencies are severe and reported even more rarely; information is therefore limited and the following discussion will be about classical homocystinuria caused by cystathionine beta synthase (CBS) deficiency. […] The enzyme cystathionine beta synthase (CBS) is necessary for conversion of homocysteine to cysteine.

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

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

  In non-pyridoxine-responsive HCU and some partially responsive patients, target tHCy can only be attained by additionally following a protein restricted diet to limit intake of the essential amino acid, methionine, the precursor to HCy production in the transsulphuration pathway. […] Remethylation defects are caused by MTHFR deficiency (known as 'MTHFR’) and disorders of cobalamin metabolism. […] Cobalamin disorders directly or indirectly impair methionine synthase activity resulting in high tHCy accompanied by a low or low/normal methionine. […] Inherited disorders of cobalamin absorption and transport include mutations in gastric intrinsic factor, the cubam receptor subunits cubilin and amnionless (Imerslund-Grsbeck syndrome) and TC-2.

• #1 Classical Homocystinuria Publications – HCU Network America

  https://hcunetworkamerica.org/publications/

  Three Main Causes of Homocystinuria: CBS, cblC and MTHFR Deficiency. What do they have in common? […] Cystathionine Beta-Synthase deficiency in E-HOD registry part 1: pyridoxine responsiveness as determinant of biochemical and clinical phenotype at diagnosis […] Estimated prevalence of moderate to severely elevated total homocysteine levels in the United States: A missed opportunity for diagnosis of homocystinuria? […] Oxidative Stress in Homocystinuria Due to Cystathionine B-Synthase Deficiency: Findings in Patients and in Animal Models […] Potential Pharmacological Chaperones for Cystathionine Beta-Synthase-Deficient Homocystinuria.

• #1

  https://scite.ai/reports/three-main-causes-of-homocystinuria-ManRGZm

  Individuals with homocystinuria, the most frequent disorder of sulfur metabolism, have many developmental and cognitive difficulties, with a significant number of cases having a learning disability, atherosclerosis, or thromboembolic disease. […] In this form there is a combined deficiency of synthesis of both methylcobalamin (methionine synthase coenzyme) and adenosyl cobalamin (methylmalonyl-CoA mutase coenzyme), with the consequent possibility of homocystinuria and methylmalonic aciduria. A massive homocystinuria with methylmalonic aciduria is characteristic of the combined deficits of the common intracellular metabolism of the B12. Isolated deficiencies of the specific metabolic pathways of adenosylcobalamin and methylcobalamin lead, respectively, to methylmalonic aciduria and homocystinuria.

• #1 Homocystinuria – UF Health

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

  Homocystinuria is inherited in families as an autosomal recessive trait. This means that the child must inherit a non-working copy of the gene from each parent to be seriously affected. […] Genetic counseling is recommended for people with a family history of homocystinuria who want to have children. Prenatal diagnosis of homocystinuria is available. This involves culturing amniotic cells or chorionic villi to test for cystathionine synthase (the enzyme that is missing in homocystinuria). […] If there are known gene defects in the parents or family, samples from chorionic villus sampling or amniocentesis can be used to test for these defects.

• #1 Homocystinuria, Beta-Synthase Deficiency | Hereditary Ocular Diseases

  https://disorders.eyes.arizona.edu/disorders/homocystinuria-beta-synthase-deficiency

  Classic homocystinuria is an autosomal recessive disorder that results from mutations in the CBS (21q22.3) gene encoding cystathionine beta-synthase. […] Numerous mutations have been identified but among the most common ones are I278T which causes a pyridoxine-responsive disorder, and the G3307S mutation which leads to a variant that is not responsive to pyridoxine treatment. […] Homocystinuria may result from a mutation in in the CBS gene.

• #1 Homocystinuria Information | Mount Sinai – New York

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

  Homocystinuria is inherited in families as an autosomal recessive trait. This means that the child must inherit a non-working copy of the gene from each parent to be seriously affected. […] Although no cure exists for homocystinuria, vitamin B therapy can help about half of people affected by the condition. […] Genetic counseling is recommended for people with a family history of homocystinuria who want to have children. Prenatal diagnosis of homocystinuria is available. This involves culturing amniotic cells or chorionic villi to test for cystathionine synthase (the enzyme that is missing in homocystinuria).

• #1 Methionine Metabolism Disorders – Pediatrics – Merck Manual Professional Edition

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

  Various defects in the remethylation process can result in homocystinuria. […] Defects include deficiencies of methionine synthase (MS) and MS reductase (MSR), delivery of methylcobalamin and adenosylcobalamin, and deficiency of methylenetetrahydrofolate reductase (MTHFR, which is required to generate the 5-methyltetrahydrofolate needed for the MS reaction). […] Because there is no methionine elevation in these forms of homocystinuria, they are not detected by neonatal screening.

• #1 Homocystinuria due to cystathionine beta synthase deficiency – Indian Journal of Dermatology, Venereology and Leprology

  https://ijdvl.com/homocystinuria-due-to-cystathionine-beta-synthase-deficiency/

  Two types of homocysteinuria have been reported based on its treatment: one is B6-responsive while the other is not. […] Treatment of B6-responsive patients includes a combination of folic acid, vitamin B12, and pyridoxine, which significantly reduces homocysteine levels. […] Treatment of B6-nonresponsive patients includes lowering of urinary levels of homocysteine and its disulphide derivative, as well as adherence to a methionine-restricted diet. […] The principles of treatment are to correct the biochemical abnormalities, especially to control the elevated plasma homocystine concentration as much as possible and to prevent or at least reduce, the complications of homocysteinuria and to prevent further complications such as thrombosis. […] Treatment with betaine provides an alternate remethylation pathway to convert excess homocysteine into methionine and may help to prevent complications, particularly thrombosis. […] As homocystinuria is a genetic disorder, frequent monitoring of blood homocysteine levels should be done and the duration of treatment should be life long.

• #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

  The majority of patients thought that the diagnosis had been delivered in a satisfactory way but the survey shows there is still room for physicians to improve their communication skills and to provide more information about the disease. […] Additional problems for patients and carers include the cumbersome procedures for obtaining medications, amino acid supplements and other dietary products and in some countries the high cost of these. […] The survey suggests that treatment of the homocystinurias is not always in line with current recommendations. […] A low-methionine diet is recommended for pyridoxine-nonresponsive CBS deficient patients, achieved by severe protein restriction and methionine-free amino acid supplements.

• #2 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. […] Variants (also called mutations) in the CBS, MTHFR, MTR, MTRR, and MMADHC genes cause homocystinuria. […] Variants in the CBS gene cause classic homocystinuria. […] Rarely, homocystinuria can be caused by variants in several other genes. […] Researchers have not determined how excess homocysteine and related compounds lead to the signs and symptoms of homocystinuria.

• #2 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. […] It is usually caused by the deficiency of the enzyme cystathionine beta synthase, mutations of other related enzymes such as methionine synthase, or the deficiency of folic acid, vitamin B12 and/or pyridoxine (vitamin B6).

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

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

  Homocystinuria is a disorder of methionine metabolism, leading to an abnormal accumulation of homocysteine and its metabolites (homocystine, homocysteine-cysteine complex, and others) in blood and urine. Homocystinuria is an autosomal recessively inherited defect in the transsulfuration pathway (homocystinuria I) or methylation pathway (homocystinuria II and III). […] Homocysteinemia may be due to a genetic predisposition to abnormal activity in the same pathways as homocystinuria. Nutritional and environmental factors, as well as specific medications, may worsen this abnormality and provoke symptoms. […] The accumulation of homocysteine and its metabolites is caused by disruption of any of the three interrelated pathways of methionine metabolismdeficiency in the cystathionine B-synthase (CBS) enzyme, defective methylcobalamin synthesis, or abnormality in methylene tetrahydrofolate reductase (MTHFR).

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

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

  Homocystinuria is a genetic disorder that causes a buildup of homocysteine in your blood and urine. […] With homocystinuria, your body lacks an enzyme that it needs to metabolize homocysteine properly and keep it within a normal range. […] Genetic changes (mutations) in many different genes cause most types of homocystinuria. A mutation in the CBS gene causes the most common type of homocystinuria. […] Mutations in the MTHFR, MTR, MTRR and MMADHC genes can also cause homocystinuria. […] Homocystinuria can also occur due to non-genetic reasons. A severe lack of vitamin B6, vitamin B9 (folate) or vitamin B12 may cause the condition.

• #2 Homocystinuria Information | Mount Sinai – New York

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

  Homocystinuria is inherited in families as an autosomal recessive trait. This means that the child must inherit a non-working copy of the gene from each parent to be seriously affected. […] Although no cure exists for homocystinuria, vitamin B therapy can help about half of people affected by the condition. […] Genetic counseling is recommended for people with a family history of homocystinuria who want to have children. Prenatal diagnosis of homocystinuria is available. This involves culturing amniotic cells or chorionic villi to test for cystathionine synthase (the enzyme that is missing in homocystinuria).

• #2 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/

  Genetic homocystinurias are a group of inborn errors of metabolism that result in the massive excretion of homocysteine (Hcy) in the urine due to Hcy accumulation in the body, usually causing neurological and cardiovascular complications. The three most frequent causes are classical homocystinuria [deficiency of cystathionine beta-synthase (CBS)], methylmalonic aciduria with homocystinuria, cblC type (cblC deficiency) and severe methylenetetrahydrofolate reductase (MTHFR) deficiency. […] Hyperhomocysteinemia (tHcy 15 M) can be caused by environmental (such as nutritional deficiency of vitamins B12 or folate) or genetic factors, including inborn errors of metabolism. […] The severe form of hyperhomocysteinemia (tHcy50 M) is rare, and typically associated with severe vitamin B12 or folate deficiency or inherited defects in Hcy metabolism.

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

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

  In addition to genetic etiologies, homocystinuria can also be caused by acquired forms of secondary to severe cobalamin (B12) deficiency. […] Homocystinuria is an autosomal recessive inherited disorder due to deficiency of cystathionine beta-synthase (EC 4.2.1.22, McKusick 236200). […] More than 320 individual homocystinuric alleles have been studied, and 100 mutations were detected. […] Deficiency of cystathionine beta-synthase leads to tissue accumulation of methionine, homocysteine, and their S-adenosyl derivatives, with lack of cystathionine and low levels of cysteine. […] The pathophysiology of cystathionine beta-synthase deficiency has not yet been completely elucidated, but accumulation of homocysteine probably plays a major role in determining some of the most relevant clinical manifestations, including generalized vascular damage and thromboembolic complications.

• #2 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. […] The most prevalent inherited disorder of homocysteine metabolism is classical HCU caused by deficiency of the pyridoxine-dependent enzyme, cystathione beta-synthase, which converts homocysteine to cystathionine in the transsulphuration pathway. […] Primary genetic disorders affecting function of CBS (classical HCU) or enzymes involved in remethylation impair metabolism of HCy causing it to rise in plasma from a reference concentration below 15 mol/L to at least 40 mol/L and usually over 100 mol/L. […] The most common causes of a high tHCy relate to underlying vitamin B12 or folate deficiency which is often first suspected when the CBC reveals a macrocytic anaemia.

• #2 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/

  This paper reviews the clinical and biochemical findings and management of the three most frequent genetic causes of homocystinurias: CBS deficiency or classical homocystinuria (HCU), methylmalonic aciduria with homocystinuria cblC type, and severe MTHFR deficiency. […] These three disorders all present with severe hyperhomocysteinemia, while Met levels are increased in HCU and decreased or normal in cblC and MTHFR deficiency, and methylmalonic acid (MMA) is increased only in cblC. […] In CBS deficient patients at diagnosis folate is often deficient likely due to the inhibition of MTHFR resulting in decreases of 5MTHF, the circulation form of folate. […] In MTHFR deficiency folate is severely deficient, whereas in cblC defect all folates accumulate as 5MTHF resulting in functional cellular folate deficiency.

• #2 Homocystinuria – Child Neurology Foundation

  https://www.childneurologyfoundation.org/disorder/homocystinuria/

  There are other nongenetic causes of high homocysteine in the blood and urine. These causes are more common than genetic causes. They can have different signs and symptoms. Nongenetic causes can include: […] Vitamin deficiencies, particularly Vitamin B6 or Vitamin B12 deficiencies […] Low thyroid hormone levels […] Diabetes […] High cholesterol […] High blood pressure […] Medications, such as carbamazepine, phenytoin, atorvastatin, methotrexate […] Smoking […] Advanced age.

• #2 Methionine Metabolism Disorders – Pediatrics – Merck Manual Professional Edition

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

  Homocysteine is an intermediate in methionine metabolism; it is either remethylated to regenerate methionine or combined with serine in a series of transsulfuration reactions to form cystathionine and then cysteine. […] Various defects in remethylation or transsulfuration can cause homocysteine to accumulate, resulting in disease. […] This disorder is caused by an autosomal recessive deficiency of cystathionine beta-synthase, which catalyzes cystathionine formation from homocysteine and serine. […] Homocysteine accumulates and dimerizes to form the disulfide homocystine, which is excreted in the urine. […] Because remethylation is intact, some of the additional homocysteine is converted to methionine, which accumulates in the blood. […] Excess homocysteine predisposes to thrombosis and has adverse effects on connective tissue (perhaps involving fibrillin), particularly the eyes and skeleton; adverse neurologic effects may be due to thrombosis or a direct effect.

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

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

  Thromboembolism has been suggested to be the end-point of homocysteine-induced abnormalities of platelets, endothelial cells, and coagulation factors. […] The risk for development of Alzheimer diseases is likely greater based on the observation that increased plasma homocysteine represents an independent risk factor.

• #2 Homocystinuria | SpringerLink

  http://link.springer.com/10.1007/978-3-540-69000-9_505

  The term homocystinuria designates a biochemical abnormality, not a specific disease entity. There are many causes of homocystinuria. […] The most common defect, cystathionine -synthase (CBS) deficiency, results in high concentrations of serum methionine (Kaye and The Committee on Genetics 2006a, b). One form of CBS deficiency is responsive to vitamin B6. Other metabolic variants of homocystinuria include defects of Vitamin B12 uptake or activation and tetrahydrofolate reductase deficiency. […] Two mechanisms probably explain most of the clinical symptoms seen: Firstly abnormal (hyper) coagulation because of sticky platelets; and secondly direct toxicity of homocysteine and its metabolites, causing endothelial cell damage.

• #2 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). […] Classic homocystinuria is caused by deficiency of cystathionine -synthase (CBS), a pyridoxine (vitamin B6)-dependent enzyme. […] Homocystinuria is inherited in an autosomal recessive manner. […] The two phenotypic variants of classic homocystinuria are B6-responsive and B6-non-responsive homocystinuria. B6-responsive homocystinuria is typically (but not always) milder than the non-responsive variant. […] „Homocystinuria” was named for excess homocystine in the urine, though now it is primarily detected by increased total homocysteine in plasma. Homocystinuria may be caused by genetically determined deficient activity of cystathionine -synthase (CBS), or a variety of genetic problems that ultimately interfere with conversion of homocysteine to methionine. […] Non-genetically determined severe dietary lack of cobalamin (vitamin B12 deficiency) may also cause „homocystinuria”.

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

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

  In a minority of cases serum B12 and folate results may not reflect whole body deficits and if deficiency is suspected, confirmatory tests are indicated. […] Once secondary causes are excluded, measurement of other amino acids in the HCy metabolic pathway, notably methionine and cystine, with quantitation of MMA in plasma or urine helps to distinguish between the genetic conditions of classical HCU and remethylation defects caused by MTHF reductase (MTHFR) or a disorder of cobalamin metabolism. […] HCU caused by CBS deficiency is the most common condition of hyperhomocystinaemia. […] Thromboembolic tendency increases in direct proportion to the magnitude and duration of HCy elevation. […] The CBS enzyme uses pyridoxal 5-phosphate as a cofactor. Approximately 50% of patients with HCU respond partially or wholly to high-dose pyridoxine (vitamin B6).

• #2 Homocystinuria, Beta-Synthase Deficiency | Hereditary Ocular Diseases

  https://disorders.eyes.arizona.edu/disorders/homocystinuria-beta-synthase-deficiency

  Classic homocystinuria is an autosomal recessive disorder that results from mutations in the CBS (21q22.3) gene encoding cystathionine beta-synthase. […] Numerous mutations have been identified but among the most common ones are I278T which causes a pyridoxine-responsive disorder, and the G3307S mutation which leads to a variant that is not responsive to pyridoxine treatment. […] Homocystinuria may result from a mutation in in the CBS gene.

• #2 CBS (homocystinemia/cystathionine beta-synthase deficiency) – newbornscreening.info

  https://www.newbornscreening.info/cbs-homocystinemia-cystathionine-beta-synthase-deficiency/

  When both parents are carriers, there is a 25% chance in each pregnancy for the child to have homocystinuria. […] About one in every 200,000 to 300,000 babies in the United States is born with homocystinuria. […] This condition occurs in all ethnic groups around the world. It is found more often in white people from the New England region of the United States. It is also more common in people with Irish ancestry.

• #2 Homocystinuria | Amino Acid Metabolism Disorder – Causes, Symptoms, Diagnosis and Treatment

  https://www.medindia.net/health/conditions/homocystinuria-amino-acid-metabolism-disorder.htm

  When CBS is deficient, homocysteine accumulates in the tissues along with its precursor amino acid methionine. […] High levels of homocysteine mainly affect supporting connective tissue in different parts of the body. […] The build-up of homocysteine also damages the supporting tissue of the body’s skeleton, and damages the connective tissue in the walls of blood vessels. […] Diagnosis is suspected during clinical examination and based on clinical suspicion diagnosis is confirmed by blood tests, imaging tests and skin biopsy. […] Genetic testing can be done to look for presence of the abnormal gene. […] It is difficult to prevent homocystinuria as this disorder occurs due to genetic mutations. […] Complications of homocystinuria may be prevented by screening of newborns with a blood test around five days within birth to check for the condition so that early treatment can be started.

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

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

  Dislocation of the optic lens, osteoporosis, thinning and lengthening of the long bones, intellectual disability, and thromboembolism are the most common features in homocystinuria due to cystathionine beta-synthase deficiency. […] There are multiple causes for homocystinuria. […] Homocystinuria is a rare inborn error of metabolism caused by mutations in the cystathionine beta-synthase gene. […] There are 2 major types of homocystinuria due to cystathionine beta-synthase deficiency based on their response to B6 (pyridoxine). […] Homocystinuria due to cystathionine beta-synthase deficiency is screened for in some newborn screening programs. […] Homocystinuria presents with elevated urinary homocysteine and plasma homocysteine. There are multiple causes that include genetic forms of inborn errors of metabolism related to interference with conversion of homocysteine to methionine and abnormalities of cobalamin transport or metabolism.

• #2 Homocystinuria – UF Health

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

  Homocystinuria is inherited in families as an autosomal recessive trait. This means that the child must inherit a non-working copy of the gene from each parent to be seriously affected. […] Genetic counseling is recommended for people with a family history of homocystinuria who want to have children. Prenatal diagnosis of homocystinuria is available. This involves culturing amniotic cells or chorionic villi to test for cystathionine synthase (the enzyme that is missing in homocystinuria). […] If there are known gene defects in the parents or family, samples from chorionic villus sampling or amniocentesis can be used to test for these defects.

• #2

  https://myhealth.alberta.ca/Health/pages/conditions.aspx?hwid=tu2113

  Homocystinuria is a rare inherited disease that causes a deficiency of one of several enzymes needed for the breakdown of food (metabolism). […] This enzyme deficiency may cause a buildup of homocysteine in the blood. […] Excess homocysteine may be released in the urine. […] People with homocystinuria may develop diseases of the heart and blood vessels at a young age. […] If homocystinuria is not diagnosed in infancy, other problems may develop, including: […] Formation of blood clots in deep veins (deep venous thrombosis, or DVT). […] Stroke.

• #2

  https://www.omim.org/entry/236200

  A number sign (#) is used with this entry because homocystinuria with or without response to pyridoxine is caused by homozygous or compound heterozygous mutation in the gene encoding cystathionine beta-synthase (CBS; 613381) on chromosome 21q22. […] 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. […] There are 2 main phenotypes of the classic disorder: a milder pyridoxine (vitamin B6)-responsive form, and a more severe pyridoxine-nonresponsive form. […] 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.

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

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

  A rare metabolic disease of methionine catabolism characterized by accumulation of methionine and homocysteine with clinical involvement of the eye, skeletal system, vascular system and central nervous system (CNS). […] The disease is caused by mutations in the CBS gene (21q22.3) leading to the accumulation of homocysteine and methionine, which are toxic for the endothelium, and causes neurocognitive impairment. […] Cysteine deficiency probably plays a role in connective tissue abnormalities, including lens dislocation.

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

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

  Homocystinuria (HCY) is a condition in which the body is unable to break down certain proteins. […] In homocystinuria (HCY), the enzymes that break down the amino acids methionine and homocysteine are not working correctly. […] In most cases of HCY, the enzyme cystathionine beta-synthase (CBS) is not working. After methionine is broken down into homocysteine, CBS helps to break down homocysteine. […] If your babys body has non-working copies of CBS, then homocysteine cannot be broken down. This causes high levels of methionine and homocysteine to build up in the body. […] HCY is an autosomal recessive genetic condition. This means that a child must inherit two copies of the non-working gene for HCY, one from each parent, in order to have the condition. The parents of a child with an autosomal recessive condition each carry one copy of the non-working gene, but they typically do not show signs and symptoms of the condition.

• #2 Homocystinuria | PPT

  https://www.slideshare.net/slideshow/homocystinuria-238455286/238455286

  Other causes Homocystinuria Caused by Defects in Methylcobalamin Formation Homocystinuria Caused by Deficiency of Methylene tetrahydrofolate Reductase. […] Homocystinuria Caused by Defects in Methylcobalamin Formation Methylcobalamin is the cofactor for the enzyme methionine synthase, which catalyzes remethylation of homocysteine to methionine. […] Homocystinuria is a disorder of methionine metabolism caused by an inability to metabolize homocysteine. […] There are three main types: classic homocystinuria caused by cystathionine -synthase deficiency; defects in methylcobalamin formation; and methylenetetrahydrofolate reductase deficiency.

• #2 Methionine Metabolism Disorders – Pediatrics – Merck Manual Professional Edition

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

  Various defects in the remethylation process can result in homocystinuria. […] Defects include deficiencies of methionine synthase (MS) and MS reductase (MSR), delivery of methylcobalamin and adenosylcobalamin, and deficiency of methylenetetrahydrofolate reductase (MTHFR, which is required to generate the 5-methyltetrahydrofolate needed for the MS reaction). […] Because there is no methionine elevation in these forms of homocystinuria, they are not detected by neonatal screening.

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

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

  Treatment depends on the underlying cause of homocystinuria. As a first step, pyridoxine (vitamin B6) responsiveness should be ascertained, because approximately 50% of patients respond to large doses of this vitamin. Nonresponsive patients with CBS deficiency should be treated with a methionine-restricted, cystine-supplemented diet. Folic acid and betaine therapy may also be helpful with all patients. In the disorders of cobalamin metabolism and transport in which methylmalonic acid and homocystine appear in the urine, hydroxycobalamin treatment (vitamin B12, not cyanocobalamin) may be beneficial.

• #2 Homocystinuria: Causes, symptoms, and tests

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

  Homocystinuria is a genetic disorder in which the body cannot break down a particular amino acid. […] The disorder passes from parents to children in an autosomal recessive manner, which means that two copies of an irregular gene must be present for it to develop. […] As homocystinuria is genetically autosomal recessive, a child must inherit a copy of the mutated gene for homocystinuria from each parent to develop the condition. […] Parents who carry just one mutated gene may not have any symptoms of homocystinuria. […] According to researchers, the child of parents who both are carriers of the gene has a 25% chance of having homocystinuria. […] The most common form of homocystinuria is called cystathionine beta-synthase (CBS). […] There is no cure for homocystinuria. However, it is possible to manage the condition with dietary restrictions, supplements, and medication. […] The only reason for genetic testing is to give people an idea of their risk of passing on a gene mutation that can lead to homocystinuria.

• #2 HIE Multimedia – Homocystinuria

  https://adamcertificationdemo.adam.com/content.aspx?productid=117&pid=1&gid=001199

  Homocystinuria is inherited in families as an autosomal recessive trait. This means that the child must inherit a non-working copy of the gene from each parent to be seriously affected. […] Genetic counseling is recommended for people with a family history of homocystinuria who want to have children. Prenatal diagnosis of homocystinuria is available. This involves culturing amniotic cells or chorionic villi to test for cystathionine synthase (the enzyme that is missing in homocystinuria).

• #3

  https://www.omim.org/entry/236200

  A number sign (#) is used with this entry because homocystinuria with or without response to pyridoxine is caused by homozygous or compound heterozygous mutation in the gene encoding cystathionine beta-synthase (CBS; 613381) on chromosome 21q22. […] 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. […] There are 2 main phenotypes of the classic disorder: a milder pyridoxine (vitamin B6)-responsive form, and a more severe pyridoxine-nonresponsive form. […] 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.

• #3 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. […] Homocystinuria is caused by a lack of the enzyme needed to metabolize homocysteine. […] Homocystinuria occurs when parents pass on to their children the defective genes that cause this disorder. […] In homocystinuria, both parents of the affected child carry 1 copy of the abnormal gene. Because usually 2 copies of the abnormal (recessive) gene are necessary for the disorder to occur, usually neither parent has the disorder.

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