Gaucher disease is an autosomal recessive
sphingolipidosis associated with deficient
glucocerebroside beta-glucosidase activity. It is a panethnic metabolic disorder, but the carrier frequency is particularly high among Ashkenazi Jews (estimated between 1:12-1:25). In order to establish a reliable and convenient biochemical assay method for differentiating asymptomatic Gaucher carriers from normal individuals,
glucocerebroside beta-glucosidase activity was determined in peripheral blood lymphocytes and cultured skin fibroblasts of 11 Gaucher obligate heterozygotes using the authentic nonlabeled
sphingolipid substrate
N-palmitoyl dihydroglucocerebroside and the artificial
fluorogenic substrate 4-methylumbelliferyl-beta-D-glucopyranoside (4MUGP). The level of lymphocyte
beta-glucosidase activity on the
glucocerebroside substrate was observed to range from 42-65% of that of the control mean, and there was no overlap of
enzyme activity between the Gaucher heterozygotes and controls. However, when the artificial
fluorogenic substrate 4MUGP was used, the level of
beta-glucosidase activity in 2 of the Gaucher obligate heterozygotes was noted to overlap with that of the control individuals. Contrary to findings in the lymphocytes, cultured skin fibroblasts appear to be a reliable
enzyme source for Gaucher carrier detection even when the artificial fluorogenic 4MUGP substrate was used, as the level of
beta-glucosidase activity in all of the Gaucher obligate heterozygotes tested was intermediate and distinctly separated from that of the control persons. Using the lymphocyte
glucocerebroside beta-glucosidase assay and fibroblast 4MUGP
beta-glucosidase assay methods, we identified the carrier status in 3 other relatives and ruled it out in 4 others. These data suggest that nonlabeled
glucocerebroside is a reliable and highly specific substrate for either lymphocyte or fibroblast
beta-glucosidase activity assay in identifying asymptomatic Gaucher carriers. Use of the 4MUGP substrate for differentiating Gaucher heterozygotes from control persons, on the other hand, should be restricted to the fibroblast
enzyme assay method, as considerable overlap of
enzyme activity was noted in lymphocytes.