Homocystinuria

Abstract

HOMOCYSTINURIA resulting from an inherited defect in methionine metabolism, although a very rare disorder, has been much publicized since its discovery in 1962. 1,2 There is now good evidence that the basic defect is a deficiency of the enzyme cystathionine synthetase, 3,4 preventing the formation of cystathionine from homocystine. The immediate result of this enzyme block is to increase accumulation of homocystine, a nonthreshold amino acid which is rapidly excreted into the urine in the oxidized form as homocystine. The back reaction to methionine, favored by the homocystine accumulation, results in high blood concentrations of the methionine and urinary excretion when tubular reabsorption limit is exceeded. Like other inborn errors of amino acid metabolism, homocystinuria often causes brain damage, the severity varying from minimal intellectual defect to gross cerebral dysfunction. Schimke et al 5 however, judged 16 of 38 patients to be of normal intelligence. Liver biopsies in two of