Genetic heterogeneity in multiple lysosomalhydrolase deficiency

An 8-year-old patient with clinical features of mucolipidosis III (pseudo-Hurler polydystrophy) andbiochemical features of mucolipidosis II (I-cell disease) is presented. Clinical findings included short stature, slightly delayed psychomotor development, progressive joint stiffness beginning at the age of three years, moderately severe Hurler-like radiologic changes (dysostosis multiplex), and cardiac murmurs indicating aortic valve disease. Urinary mucopolysaccharides were normal. Biochemical findings in cultured fibroblasts included abnormal accumulation of ³⁵S-acid mucopolysaccharides, deficiencies for multiple acid hydrolases, and excessive levels of these enzymes in the cell culture medium. Phase microscopy of cultured fibroblasts revealed typical I-cell-like inclusions. The patient's serum showed 7 to 70 fold elevations of several acid hydrolases. Serum hydrolase measurements are recommended as the simples diagnostic test for multiple lysosomal hydrolase deficiency in any patient whose short stature, joint stiffness, and dysostosis multiplex suggest a Hurler-like condition but whose urinary mucopolysaccharides are not elevated.