Disorders of Glycosaminoglycan Metabolism (Mucopolysaccharidoses)

Abstract

Proteoglycans are hybrid molecules consisting of a carbohydrate moiety, the glycosaminoglycans, and a protein component. The mucopolysaccharidoses (MPSs) are inborn genetically determined disturbances of glycosaminoglycan metabolism. Of the eight known types of acid mucopolysaccharides, which differ from each other in their mucosaccharide component, their sulfate content, and the type of linkage of the mucosaccharide units, four are involved in the storage process in the MPSs. The MPSs are ingested into the cell through receptor-mediated endocytosis and digested by lysosomal enzymes. The disturbances of mucopolysaccharide metabolism are caused by a failure of the degradation of the repeated disaccharide units to monomers. The defects involve only one of the chain of enzymes of the catabolic pathway. Different forms of MPSs arise according to the nature of the enzyme defect, in each of which a specific mucopolysaccharide is excreted in the urine. All MPSs are inherited as autosomal-recessive traits, with the exception of type II (Hunter's syndrome), which is X linked. All MPSs may affect the nervous system. Types I-S, IV, and VI are not associated with mental retardation, but may be present with other neurological symptoms. Enzymes missing in diseased fibroblasts are secreted by normal cells, taken up by the abnormal fibroblasts, and incorporated into their lysosomes, where they display their hydrolytic activity. These observations are of diagnostic importance, since they can be used to classify the unknown MPS.