Genetic defects of the degradation of glycosaminoglycans: the mucopolysaccharidoses

Abstract

Elsewhere in this volume the clinical characteristics and genetics of the mucopolysaccharidoses are discussed. Extensive reviews of historical aspects, clinical features and pathology have been published (Dorfman and Matalon, 1972; Spranger, 1972; McKusick, 1972). Modern understanding of the metabolic basis of these diseases started with the demonstration by Brante (1952) that livers of patients with Hurlers disease contain increased quantities of substances composed of hexosamine, uronic acid and sulphate. More definitive evidence of involvement of glycosaminoglycans became available when Dorfman and Lorincz (1957) discovered that dermatan sulphate and heparan sulphate were excreted in large amounts in the urine of a patient with the Hurler syndrome. Although it was clear on genetic grounds that Hunter’s and Hurler’s syndromes represented different mutations, the distinction of individual mucopolysaccharidoses on chemical grounds was established after Harris (1961) and Sanfilippo, Podosin, Langer and Good (1963) observed that the excessive urinary excretion of only heparan sulphate was characteristic of a distinctive clinical entity. The classification of the mucopolysaccharidoses by McKusick et al (1965) served to clarify the concept that the mucopolysaccharidoses consisted of a group of clinically distinct diseases.