Is multiple sulphatase deficiency due to defective regulation of sulphohydrolase expression?

Abstract

Multiple sulphatase deficiency disease is an unusual autosomal recessive disorder characterised biochemically by a deficiency of several sulphohydrolase activities^1,2. The laboratory diagnosis of this combined neurological connective tissue disorder is made on the basis of decreased activities of the lysosomal enzymes, arylsulphatase A and arylsulphatase B and the microsomal enzyme, arylsulphatase C. The primary defect in this multi-enzyme deficiency has not been identified. Using immunological techniques to characterise further the residual activities of aryl-sulphatases A and B in the multiple sulphatase deficiency disease, we have examined the levels of cross-reacting material (CRM) to arylsulphatases A and B in cultured skin fibroblasts from controls and patients with multiple sulphatase deficiency, metachromatic leukodystrophy (deficiency of only arylsulphatase A activity) and Maroteaux–Lamy syndrome (deficiency of only arylsulphatase B activity). We report here results indicating that arylsulphatases A and B in multiple sulphatase deficiency are reduced in their levels of CRM while retaining a normal activity/CRM ratio. Because the two enzymes are apparently structurally unrelated, these data are consistent with the possibility that their combined deficiencies in this disorder may result from a defect in the coordinated expression of sulphohydrolases.