homocystinuria
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Etiology
- hereditary homozygous enzyme deficiency
- cystathionine beta-synthase (most common)
- methylene tetrahydrofolate reductase
- cobalamin reductase* (cbl C, D)
- MMACHC deficiency (cblC)
- methyltransferase-associated cobalamin reductase (cbl E, G)
- transport of cobalamin out out lysozymes (cblF)
* Also associated with methylmalonic acidemia
Epidemiology
- > 45 patients, mostly children have been described
Pathology
- intimal fibrosis
- destruction of arterial elastic fibers
- aortic & pulmonary arterial dilatation
- destruction of zonular fibers of lens
- fatty liver
- gliosis
- focal necrosis of midbrain
- thrombosis
- osteoporosis
Genetics
- autosomal recessive inheritance
- associated with defects in CBS
Clinical manifestations
- mental retardation
- seizures
- spasticity
- cataracts
- lenticular subluxation
- sparse hair
- arachnodactyly (older patients)
- pectus excavatum
- long, thin, trunk, arms, & legs
- thromboembolic episodes
- osteoporosis
Laboratory
- cerebrospinal fluid
- increased levels of homocysteine
- increased levels of methionine
- serum
- increased levels of homocysteine
- increased levels of methionine
- urine
- increased levels of homocysteine
- increased levels of methionine
- serum methylmalonic acid elevation with cobalamin reductase deficiency
- complete blood count -> pancytopenia
- CBS gene mutation
- cystathionine beta-synthase in fibroblasts
Management
- Early diagnosis in infancy is key
- methionine-restricted, cystine supplemented diet
- treated infants have clinically benign course
- vitamin B6 25-500* mg/day
* This dose is harmless[2]
More general terms
More specific terms
Additional terms
- 5,10-methylenetetrahydrofolate reductase (MTHFR)
- cobalamin reductase
- cystathionine beta-synthase (serine sulfhydrase, beta-thionase, CBS)
- homocystine
- hyperhomocysteinemia
- methylmalonic acidemia/aciduria