High prevalence of the 1278T mutation of the human cystathionine beta-synthase detected by a novel screening application

Classical homocystinuria due to cystathionine beta-synthase deficiency is o ne of the disorders revealing a high risk of thromboembolic events and vasc ular disease. This autosomal-recessively inherited metabolic disorder is co nsidered to be rare with an estimated prevalence of 1:130.000 in the German population. In this study. we developed a novel multiplex PCR generating a llele specific fragment lengths to analyst: individual genotypes of the two most frequent cystathionine beta:synthase alterations, the I278T mutation, which is worldwide found on up to the half of homocystinuric alleles, and the adjacent polymorphism 844ins68. Screening of 200 unrelated German contr ol subjects revealed a frequency of heterozygosity of 1.5% for I278T corres ponding to a calculated frequency of homozygosity of 1.17.800. Our data ind icate that homocystinuria due to cystathionine beta -synthase deficiency is a frequently unrecognized disorder resulting in a high risk of thromboembo lic events.