Heterozygote detection of Type I Gaucher disease using blood platelets

Abstract

This report describes a reliable and reproducible method for the identification of carriers of Type I Gaucher disease using blood platelets as the source of β-glucosidase and 4-methylumbelliferyl-β- d-glucoside as substrate. Platelet lysates have at least two identifiable β-glucosidase activities with the synthetic substrate. One is maximally active at pH 5.0 in the absence of sodium taurocholate and the other at pH 5.6 in the presence of taurocholate. In platelets of Gaucher homozygotes and heterozygotes, the β-glucosidase activity at pH 5.6 with the bile salt is reduced whereas the activity at pH 5.0 is the same in non-carriers, carriers and affected patients. In addition to differences in specific activity, the ratio of β-hexosaminidase to βglucosidase activities is a useful parameter in the evaluation of the carrier state. Since carriers have normal activity of hexosaminidase and a reduced activity of β-glucosidase, their mean activity ratio is about 70% higher than in non-carriers. Therefore we propose that the specific activity of β-glucosidase at pH 5.6 in the presence of sodium taurocholate with the. ratio of β-hexosaminidase to β-glucosidase serve as useful and reliable indices in the evaluation of the carrier state for Gaucher disease.