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homocystinuria
Etiology:
- hereditary homozygous enzyme deficiency
a) cystathionine beta-synthase (most common)
b) methylene tetrahydrofolate reductase
c) cobalamin reductase* (cbl C, D)
- MMACHC deficiency (cblC)
d) methyltransferase-associated cobalamin reductase (cbl E, G)
e) transport of cobalamin out out lysozymes (cblF)
* Also associated with methylmalonic acidemia
Epidemiology:
- > 45 patients, mostly children have been described
Pathology:
1) intimal fibrosis
2) destruction of arterial elastic fibers
3) aortic & pulmonary arterial dilatation
4) destruction of zonular fibers of lens
5) fatty liver
6) gliosis
7) focal necrosis of midbrain
8) thrombosis
9) osteoporosis
Genetics:
- autosomal recessive inheritance
- associated with defects in CBS
Clinical manifestations:
1) mental retardation
2) seizures
3) spasticity
4) cataracts
5) lenticular subluxation
6) sparse hair
7) arachnodactyly (older patients)
8) pectus excavatum
9) long, thin, trunk, arms, & legs
10) thromboembolic episodes
11) osteoporosis
Laboratory:
1) cerebrospinal fluid
a) increased levels of homocysteine
b) increased levels of methionine
2) serum
a) increased levels of homocysteine
b) increased levels of methionine
3) urine
a) increased levels of homocysteine
b) increased levels of methionine
4) serum methylmalonic acid elevation with cobalamin reductase deficiency
5) complete blood count -> pancytopenia
6) CBS gene mutation
7) cystathionine beta-synthase in fibroblasts
Management:
1) Early diagnosis in infancy is key
2) methionine-restricted, cystine supplemented diet
-> treated infants have clinically benign course
3) vitamin B6 25-500* mg/day
* This dose is harmless [2]
Related
5,10-methylenetetrahydrofolate reductase (MTHFR)
cobalamin reductase
cystathionine beta-synthase (serine sulfhydrase, beta-thionase, CBS)
homocystine
hyperhomocysteinemia
methylmalonic acidemia/aciduria
Specific
methylmalonic aciduria & homocystinuria
General
inborn error of metabolism
Database Correlations
OMIM correlations
References
- DeGowin & DeGowin's Diagnostic Examination, 6th edition,
RL DeGowin (ed), McGraw Hill, NY 1994, pg 895
- Harrison's Principles of Internal Medicine, 13th ed.
Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 1038,
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