Immunochemical studies on cultured fibroblasts from patients with homocystinuria due to cystathionine beta-synthase deficiency.

Fibroblast extracts from 20 individuals with homocystinuria due to cystathionine beta-synthase deficiency were analyzed for the presence of immunoreactive synthase antigen as cross-reacting material (CRM). CRM was quantitated by competitive and direct immunotitration using rabbit antiserum against homogeneous human liver synthase. The lower limit of sensitivity for detection of CRM was 1.5% of the amount of synthase antigen in control extracts. Each of 14 mutant extracts with detectable synthase activity had detectable CRM ranging from 5% to 100% of the amount found in control extracts. No statistically significant correlation was observed between the percent residual activity and the percent CRM. Of six mutant extracts without measurable catalytic activity, three had no detectable CRM, while three had 13%, 17%, and 26% CRM, respectively. These results extend our information about the biochemical heterogeneity previously found in synthase deficiency, and emphasize that such deficiency is caused by a wide array of mutations affecting the structural locus for cystathionine beta-synthase.