Gargoylism, mucopolysaccharides

There are numerous inherited disorders of lysosomal metabolism in humans. These disorders result from the lack of a specific acid hydrolase and have several clinical manifestations. A variety of substances may accumulate that interfere with normal cell functions, as is the case with the lipidoses (Chapter 9) or mucopolysaccharides (glycosaminoglycans) in the Hurler s disease (gargoylism). 

The urine of patients with gargoylism, of both the autosomal recessive and sex-linked types, contains abnormally high amounts of acid mucopolysaccharides. Determination (T2) of the acid mucopolysaccharides in urine in relationship to preformed creatinine is useful in distinguishing certain cases of gargoylism from other conditions with which they are sometimes clinically confused (e.g., cretinism and chondro-osteo-dystrophies of the Morquio-Brailsford type). Another simple diagnostic test for gargoylism is based on the presence in the lymphocytes of abnormal inclusions of acid mucopolysaccharides which are revealed by staining (M24). 

Although the therapy of gargoylism is not well advanced, the discovery (Lll) of an apparently related heritable disorder of acid mucopolysaccharide metabolism in cattle may facilitate study of the pathogenesis and the therapy of this condition. 

M21. Meyer, K., Hoffman, P., Linker, A., Crumbach, M. M., and Sampson, F., Sulfated mucopolysaccharides of urine and organs in gargoylism (Hurler s syndrome) II. Additional studies. Proc. Soc. Exptl. Biol. Med. 102, 587-590 (1959). 

M24. Mittwoch, U., Inclusions of mucopolysaccharide in the lymphocytes of patients with gargoylism. Nature 191, 1315-1316 (1961). 

W7. Wessler, E., Determination of acidic glycosaminoglycans (mucopolysaccharides) in urine by an ion exchange method. Application to coUagenoses , gargoylism, the nail-patella syndrome and Farber s disease. Clin. Chim. Acta 16,235-243 (1967). 

Since ganglioside storage is observed in gargoylism (Pfaundler-Hurler syndrome), this disease will be considered under the heading of gangliosidoses, although the complex disturbance of lipid and mucopolysaccharide metabolism in gargoylism is still poorly understood. 

On the basis of quantitative and qualitative abnormalities of the amino acids of urinary chondroitinsulfate B in gargoylism, Dorfman (1963, 1966) suspects a deficiency of its protein binding with the result that chondroitinsulfate is not retained properly in connective tissues, leading to increased concentrations in serum, organs, and urine. Studies on mucopolysaccharides are limited by methodological difficulties, and artefacts may result from their complexity and their particular physicochemical state. 

Meyer, K., M. M. Grumbach, A. Linker, and P. Hoffman Excretion of sulfated mucopolysaccharides in gargoylism (Hurlers syndrome). Proc. Soc. exp. Biol. (N.Y.) 97, 275 (1958). Minkowitz, S. A new form of visceral histiocytic glycolipidosis with mental retardation. Amer. J. Med. 37, 623 (1964). 

Mittwoch, U. Inclusion of mucopolysaccharides in the patients with gargoylism. Nature (Lond.) 191,1315 (1961). 

---