The Degradation of Acid Mucopolysaccharides and the Mucopolysaccharidoses
Since the original clinical descriptions by Hunter (18) and Hurler (19), a vast literature has appeared which is concerned with a group of genetic diseases characterized by the accumulation in tissues and excretion in urine of acid mucopolysaccharides. These studies have been reviewed by McKusick (28) and Dorfman and Matalon (11,12). The term mucopolysaccharidoses was originally suggested by Brante (1) who discovered that the storage material present in livers of Hurler patients contained the characteristic components of acid mucopolysaccharides. Subsequently, Dorfman and Lorincz (10) showed that heparan sulfate and dermatan sulfate were excreted in large quantities in the urine of patients with Hurler’s syndrome. The basis of accumulation of acid mucopolysaccharides in these diseases has been subject to much speculation. The discovery by Van Hoof and Hers (31) of distended lysosomes in livers of patients with Hurler’s disease and the demonstration by Neufeld and coworkers (4,15,16,17,22,29,32) of the existence of “corrective factors” has strongly indicated the probability that these diseases result from deficiency of lysosomal acid hydrolases. However, in contrast to the lipid storage diseases, limited knowledge is available concerning the specific enzymic defects of the mucopolysaccharidoses. To some extent this is due to inadequate information regarding the normal catabolic pathways of these compounds and lack of knowledge concerning the detailed structure of the accumulated polysaccharides.
KeywordsHyaluronic Acid Heparan Sulfate Dermatan Sulfate Acid Mucopolysaccharide Hunter Syndrome
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- 6.Cifonelli, J. A., Matalon, R. and Dorfman, A. L-iduronidase in human tissues, urine and cultured fibroblasts. Fed. Proc. 30: 1207 (1971).Google Scholar
- 7.Dische, Z. A new specific color reaction of hexuronic acids. J. Biol, Chem. 167: 189 (1947).Google Scholar
- 8.Dorfman, A. The kinetics of the enzymatic hydrolysis of hyaluronic acid. J. Biol. Chem.172: 377 (1948).Google Scholar
- 12.Dorfman, A. and Matalon, R. The mucopolysaccharidoses. In: The Metabolic Basis of Inherited Diseases, J. B. Stanbury, J. B. Wyngaarden and D. S. Frederickson (Eds.), 3rd Edition, New York, McGraw Hill, in press.Google Scholar
- 14.Fransson, L. –Å., Sjöberg, I., and Dorfman, A. In Preparation.Google Scholar
- 18.Hunter, C. A rare disease in two brothers. Proc. Roy. Soc, Med. 10: 104 (1917).Google Scholar
- 23.Lindahl, U. and Axelsson, O. Identification of iduronic acid as the major sulfated uronic acid of heparin. J. Biol. Chem. 246: 74 (1970).Google Scholar
- 27.Matalon, R. and Dorfman, A. Unpublished data.Google Scholar
- 28.McKusick, V. A. Heritable Disorders of Connective Tissue, 3rd Ed., St. Louis, Mosby, 1966.Google Scholar
- 31.Van Hoof, F. and Hers. H. G. The ultrastructures of hepatic cells in Hurler’s disease (gargoylism), Comp. Rend. Acad. Sci. 259: 1281 (1964).Google Scholar