Cerebroside sulfate hydrolysis by fibroblasts from a parent with metachromatic leukodystrophy

Abstract

A GENERALIZED deficiency of arylsulfatase A, necessary for normal turnover of cerebroside sulfate, prevails in all types of metachromatic leukodystrophy. The usual enzyme assay techniques have failed to differentiate biochemically the three types of disorders? We have found that fibroblasts provided with exogenous cerebroside sulfate during growth accumulated the sulfolipid intracellulady. Control cells with a normal complement of arylsulfatase A hydrolyzed the sulfatide; late infantile MLD cells showed no hydrolysis; adult MLD cells showed about half-normal rates of hydrolysis; and juvenile MLD cells showed hydrolysis rates intermediate between those of late infantile and adult cells? The sulfatide loading thus provided a test system with greatly increased sensitivity compared to cell or tissue extract enzyme assay technique s . This loading test has also been useful for establishing whether the enzyme present in extracts of cells derived from patients with atypical MLD was indeed functional in the intact, growing cells} 3 Recently, several subjects who were obligate heterozygotes, but otherwise healthy, were found to be profoundly deficient in arylsulfatase A. Dubois et al 4 noted that a father of twins affected with MLD had leukocyte arylsulfatase A in the same low range as the twins. Three unaffected siblings of the twins also had the same deficiency. Lott et aP observed that a father of two children with MLD and a mother in another family with three affected children had the enzyme deficiency in