569 BETA-GLUCOSIDASE ACTIVITY IN CULTURED SKIN FIBROBLASTS FROM CONTROLS AND PATIENTS WITH GAUCHER'S DISEASE

Abstract

Gaucher's disease is a group of autosomal recessive disorders involving the storage of glucosylceramide because of a deficiency of glucosylceramide β-glucosidase activity. The clinical pictures range from the non-neuronopathic form with variable symptoms ranging from mild to severe (Type 1), acute neuronopathic form with severe visceral and CNS involvement (Type 2) and sub-acute neuronopathic form with less severe visceral and CNS involvement (Type 3). A study of β-glucosidase activity has been aimed at defining a method for predicting the clinical type before symptoms are obvious. This is especially true of samples received from 2-4 year old patients who are still free of neurological symptoms. Beta-glucosidase activity has been measured in cultured skin fibroblasts using 4-methylumbelliferyl-β-D-glucopyranoside and ¹⁴C-glucose-labeled glucosylceramide. Kinetic studies using ¹⁴C-glucosylceramide and pure sodium taurocholate of varying concentrations have provided evidence for two β-glucosidases. Using either 5-7 nmoles or 60-65 nmoles of glucosylceramide, controls and patients with all clinical types of Gaucher's disease were studied. Type 2 patients had less residual activity when the higher substrate concentration was used than when the lower concentration was used. The Type 1 patients did not show this difference. This effect was not observed with the fluorogenic substrate.

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