An improved fluorometric leukocyte [beta]-glucosidase assay for Gaucher's disease

Abstract

Three fluorometric leukocyte [beta]-glucosidase assays were compared for their ability to diagnose Gaucher's disease and identify carriers of the disorder: the acid [beta]-glucosidase assay of Beutler and Kuhl [2], a pH 5.5-sodium taurocholate-dependent assay and a new procedure which employs conduritol B epoxide, an active-site specific inhibitor of glucocerebrosidase. All three assays unambiguously identified patients with Gaucher's disease. With regard to identifying carriers the bile saltdependent assay of Peters et al. and the conduritol B epoxide-dependent procedure gave the greatest discrimination between the mean [beta]-glucosidase values for the control and heterozygote samples when evaluated using Student's t test. The most reliable assay for the identification of the carrier state was the conduritol B epoxide-dependent procedure which can be expected to provide the fewest false negative results when classifying heterozygotes (5%). However, the fact that none of these methods will completely separate control and heterozygote samples indicates that their use in screening programs will result in a significant number of incorrect assignments.