Genetic complementation studies of multiple sulfatase deficiency.

Abstract

Cultured fibroblasts from 2 individuals with multiple sulfatase deficiency (MSD) had decreased activities of arylsulfatases (aryl-sulfate sulfohydrolase, EC 3.1.6.1) A, B and C, and iduronate-sulfate sulfatase, sulfamidase and N-acetylglucosamine-6-sulfate sulfatase. The activity of N-acetylgalactosamine-6-sulfate sulfatase was decreased in one line but not in the other. Mixtures of MSD cell extracts with extracts from normal cells did not result in inhibition of normal sulfatase activities. Mixtures of MSD cell extracts with extracts of fibroblasts from patients with Hunter or Sanfilippo A syndrome did not activate iduronate-sulfate sulfatase or sulfamidase activity. Heterokaryons formed by fusion of MSD cells with Sanfilippo A fibroblasts demonstrated a partial correction of the enzyme deficiency. In a similar manner, MSD-Hunter heterokaryons showed a significant increase in iduronate-sulfate sulfatase activity. Genetic complementation in heterokaryons of MSD fibroblasts and cells of either Sanfilippo A or Hunter syndrome implies a genetic defect in MSD different from that causing specific sulfatase deficiencies.