Ithe Diagnostic Value of Isolated Urinary Mucopolysaccharides and of Lymphocyte Inclusions in Gargoylism

Gargoylism or Hurler's syndrome (Hunter, 1917; Hurler, 1919) is a rare genetically determined disease (McKusick, 1960) appearing in autosomal recessive and sex-linked forms. Two of the six known sulphated mucopolysaccharides are produced in excess, namely chondroitin sulphate B and heparitin sulphate. They accumulate in most organs of the body, especially in the liver and the spleen (Meyer, Grumbach, Linker and Hoffman, 1958; Meyer, Hoffman, Linker, Grumbach and Sampson, 1959). They appear as metachromatic deposits which, however, are very soluble in routine fixatives so that liver biopsies might show vacuoles unless they are fixed by special techniques (Haust and Landing, 1961). Both mucopolysaccharides are excreted in large amounts in the urine (Dorfman and Lorincz, 1957; Lorincz, 1958) and being resistant to hyaluronidase, are distinguishable from the mucopolysaccharides of normal urine, which are excieted only in small amounts (Di Ferrante and Rich, 1956). It has been found that a proportion of the lymphocytes of such patients contains abnormal cytoplasmic inclusions (Mittwoch, 1959, 1961) which can be seen in preparations stained with May-GrunwaldGiemsa. They also stain metachromatically with toluidine blue. These staining reactions agree with the assumption that the inclusions consist of acid mucopolysaccharides. Up to the present the lymphocyte inclusions have been found in a total of 22 patients, in whom a diagnosis of gargoylism had been suggested. In the present investigation these inclusions have been correlated with the presence of abnormal amounts of hyaluronidase-resistant mucopolysaccharides in the urine. Some of the clinical findings on the patients investigated by both methods are summarized in Table 1. Table 2 summarizes the clinical findings of the other patients in whom lymphocyte inclusions were found, without biochemical investigation. Reports on some of the cases have already been published: five cases in Table 2 and Case 2 of Tables 1 and 3 (Mittwoch, 1959); Cases 1, 3, 6 and 7 (Mittwoch, 1961).