CYSTATHIONINE-BETA-SYNTHASE DEFICIENCY - DETECTION OF HETEROZYGOTES BY THE RATIOS OF HOMOCYSTEINE TO CYSTEINE AND FOLATE

Elevated total plasma homocysteine (tHcy) is recognized as an independ ent risk factor for occlusive vascular disease. However, it is not kno wn how much of the observed hyperhomocysteinemia in patients with vasc ular disease is due to heterozygosity for cystathionine-beta-synthase (C beta S) deficiency, because a clinically useful screening method is unavailable. To determine this, parents of children who are homozygou s for C beta S deficiency (affected with homocystinuria) and a control population were compared for tHcy, total plasma cysteine (tCys), plas ma folate, and plasma vitamin B-12. The group of obligate heterozygote s had increased tHcy (P less than or equal to .01), decreased tCys (P less than or equal to .01), and decreased plasma folate (P less than o r equal to .01). The calculated ratios of tHcy/tCys (P = .01) and tHcy /plasma folate (P = .003) were the best metabolic discriminants for ge notype, These ratios are likely to prove useful in heterozygote screen ing for C beta S deficiency and in the development of rational treatme nt strategies for patients with increased tHcy. Copyright (C) 1998 by W.B. Saunders Company.