Homocystinuria and homocystinemia without hypermethioninemia, but with recurrent episodes of folate responsive schizophrenic-like behavior, was documented in a mildly retarded adolescent girl who lacked the habitus associated with cystathionine synthase deficiency. Enzymes involved in homocysteine-methionine metabolism were demonstrated to be normal. A defect in the ability to reduce N-5–10-methylenetetrahydrofolate to 5-methyltetrahydrofolate was demonstrated. Methylenetetrahydrofolate reductase was 18 per cent of control values. Methyltetrahydrofolate is used for the methylation of homocysteine to methionine, and a deficiency of this compound could explain the homocystinemia and homocystinuria. (N Engl J Med 292: 491–496, 1975), THE most frequently encountered cause of homocystinuria, an aminoaciduria described in 1962,1,2 has been deficient activity of cystathionine-β-synthase (E.C.188.8.131.52), the enzyme that catalyzes the condensation of homocysteine with serine.3 However, homocystinuria has also been described as a consequence of defects in the methylation of homocysteine to methionine4,5 and of the administration of 6-azauridine triacetate.6 The case reported below concerns a girl with a previously unrecognized cause of homocystinuria: a deficient activity of 5,10-methylenetetrahydrofolate reductase (E.C.184.108.40.206). This enzyme is necessary for the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a compound that serves as the methyl donor for the methylation of homocysteine to.
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