Adult Gaucher's disease: kindred studies and demonstration of a deficiency of acid beta-glucosidase in cultured fibroblasts.

Two phenotypically different forms of Gaucher's disease exist, a chronic non-cerebral form (adult Gaucher's disease) and an infantile cerebral form (infantile Gaucher's disease). In the majority of kindreds, transmission of both disorders is consistent with autosomal recessive inheritance. Glucocerebroside accumulates in both disorders, and a striking deficiency of glucocerebrosidase is present: the degree of deficiency is greater in one case of infantile Gaucher's disease than in adult Gaucher's disease [1]. The deficiency of glucocerebrosidase in adult Gaucher's disease was first demonstrated by Brady et al. [2] in spleen, using isotopically labeled glucocerebroside as substrate. Patrick [3] confirmed this finding using nonlabeled glucocerebroside and also reported that P-glucosidase activity, assayed with p-nitrophenyl-(3-D-glucopyranoside, was similarly deficient. Subsequently, the fluorogenic substrate, 4-methylumbelliferyl-(3-D-glucopyranoside, was successfully employed to demonstrate the deficiency of P-glucosidase in liver and spleen [4] and leukocytes [5] from patients with adult Gaucher's disease. Beutler and Kuhl demonstrated that the pH activity curve of (3-glucosidase in normal leukocytes had two optima, one at pH 4.0 and the other at pH 5.0. Leukocytes from patients with Gaucher's disease were preferentially deficient in the peak at pH 4.0 This was the first evidence for the existence of more than one form of