Homocystinuria
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| Homocystinuria | |
|---|---|
| Classification and external resources | |
 Homocysteine |
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| ICD-10 | E72.1 |
| ICD-9 | 270.4 |
| OMIM | 236200 |
| DiseasesDB | 5991 |
| MedlinePlus | 001199 |
| eMedicine | derm/708 |
| MeSH | D006712 |
Homocystinuria, also known as cystathionine beta synthase deficiency or CBS deficiency,[1] is an inherited disorder of the metabolism of the amino acid methionine, often involving cystathionine beta synthase. It is an inherited autosomal recessive trait, which means a child needs to inherit a copy of the defective gene from each parent to be affected.
Contents |
[edit] Presentation
This defect leads to a multisystemic disorder of the connective tissue, muscles, CNS, and cardiovascular system. Homocystinuria represents a group of hereditary metabolic disorders characterized by an accumulation of 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.
[edit] Possible Signs and symptoms
- A family history of homocystinuria[2]
- Flush across the cheeks
- Musculoskeletal
- Tall, thin build (resembling Marfanoid habitus)[1]
- Long limbs (dolichostenomelia)
- High-arched feet (pes cavus)
- Knock-knees (genu valgum)
- Pectus excavatum and Pectus carinatum
- Mental retardation
- Seizures
- Psychiatric disease
- Eye anomalies:
- ectopia lentis (downward dislocation)[3] or subluxation of lens
- Myopia (Nearsightedness)
- Glaucoma
- Optic atrophy
- Vascular disease
- extensive atheroma formation at young age which affects many arteries but not the coronary arteries
- Intra vascular thrombosis
[edit] Mortality/morbidity
The life expectancy of patients with homocystinuria is reduced only if untreated. It is known that before the age of 30, almost one fourth of patients die as a result of thrombotic complications (e.g. heart attack).
[edit] Treatment
No specific cure has been discovered for homocystinuria; however, many people are treated using high doses of vitamin B6 (also known as pyridoxine).[4] Slightly less than 50% respond to this treatment and need to intake supplemental vitamin B6 for the rest of their lives. Those who do not respond require a low methionine diet, and most will need treatment with trimethylglycine. A normal dose of folic acid supplement and occasionally adding cysteine to the diet can be helpful.
Betaine (N,N,N-trimethylglycine) is used to reduce concentrations of homocysteine by promoting the conversion of homocysteine back to methionine. The re-formed methionine is then gradually removed by incorporation into body protein. The methionine that is not converted into protein is converted to S-adenosyl-methionine which goes on to form homocysteine again. Betaine is, therefore, only effective if the quantity of methionine to be removed is small. Hence treatment includes both betaine and a diet low in methionine. In classical homocystinuria (CBS) the plasma methionine usually increases above the normal range of 30 micromoles/L and the concentrations should be monitored as potentially toxic levels (more than 400 micromole/l) may be reached.
[edit] Recommended diet
Low-protein food is recommended for this disorder, which requires food products low in particular types of amino-acid (e.g. methionine).
[edit] See also
[edit] External links
- Homocystinuria Support
- GeneReview/NIH/UW entry on Homocystinuria Caused by Cystathionine Beta-Synthase Deficiency
- Paper and discussion on Homocystinuria due to Cystathionine Beta Synthase deficiency
[edit] References
- ^ a b Online 'Mendelian Inheritance in Man' (OMIM) 236200
- ^ Maillot F, Kraus JP, Lee PJ (2008). "Environmental influences on familial discordance of phenotype in people with homocystinuria: a case report". J Med Case Reports 2 (1): 113. doi:10.1186/1752-1947-2-113. PMC 2377250. PMID 18423051. http://www.jmedicalcasereports.com/content/2//113.
- ^ Peter Nicholas Robinson; Maurice Godfrey (2004). Marfan syndrome: a primer for clinicians and scientists. Springer. pp. 5–. ISBN 9780306482380. http://books.google.com/?id=eX4B9WASDpAC&pg=PA5. Retrieved 12 April 2010.
- ^ Bakker, R. C.; Brandjes, D. P. (Jun 1997). "Hyperhomocysteinaemia and associated disease". Pharmacy world & science : PWS 19 (3): 126–132. doi:10.1023/A:1008634632501. PMID 9259028.
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