Homocystinuria with methylmalonic aciduria: Two cases in a sibship

Abstract The clinical and biochemical findings in two brothers each of whom has homocystinuria and methylmalonic aciduria are described. Studies of fibroblasts grown from skin biopsies of these patients demonstrated that their homocystinuria is due to decreased activity of N 5 -methyltetra-hydrofolate methyltransferase, rather than due to decreased activity of cystathionine synthase. These siblings are the second and third reported cases of homocystinuria due to a defect in homocysteine methylation. Both the means and importance of differentiating homocystinuria due to cystathionine synthase deficiency from that due to defects in methylation of homocysteine are discussed. The cause of the methylmalonic aciduria has not been finally established, although the data are compatible with a partial decrease in activity of methylmalonyl-CoA isomerase. Together, the abnormalities in these brothers may tentatively be ascribed to a defect in the uptake or early metabolism of B 12 , the condition most likely being inherited as an autosomal recessive trait.