GM1-gangliosidosis: abnormalities in biosynthesis and early processing of beta-galactosidase in fibroblasts.

Biosynthesis and early processing of beta-galactosidase were analyzed by pulse-chase technique in human fibroblasts. In normal cells, an 84 kDa precursor was processed first to an intermediate form of higher molecular weight (88 kDa), and then to a 64 kDa mature enzyme. This intermediate form was detected also in the culture medium. Biosynthesis of the precursor was apparently normal in four cases of GM1-gangliosidosis, and a precursor of abnormally high molecular weight (86 kDa) was observed in one case. No further processing occurred to the 88 kDa form. It was concluded that the enzyme deficiency was caused by heterogeneous molecular mutations of beta-galactosidase with a defect in early processing in this disease.