ALPHA-L-IDURONIDASE DEFICIENCY IN A CAT - MODEL OF MUCOPOLYSACCHARIDOSIS-I

A 1-yr-old male domestic shorthair cat was referred to the University of Pennsylvania Veterinary Hospital with a history of progressive lameness. The cat had a short, broad face, frontal bossing, a depressed nasal bridge, small ears, bilateral corneal clouding, and thickened skin over the dorsal aspect of his neck. Radiographically, the cervical vertebrae were wide, assymetrical, and appeared nearly fused; there was bilateral coxofemoral subluxation and pectus excavatum. Electrophoresis of glycosamino- glycans (GAG) from the urine revealed an excess of both dermatan sulfate and heparan sulfate. The incorporation of35SO4 into the GAG of fibroblasts revealed an exaggerated accumulation of [35S] -glycosaminoglycans. By light microscopy, neurons swollen with vacuolated cytoplasm were observed. By electron microscopy, the spinal cord neurons contained membrane-bound “zebra bodies”. Membrane-bound inclusions containing granular material or an occasional myelin-like figure were present in hepatocytes. The activities of seven lysosomal hydrolases (α-L-iduronidase EC. 3.2.1.76, β-D-glucuronidase EC. 3.2.1.31, arylsulfatase A EC. 3.1.6.1, arylsulfatase B EC. 3.1.6.1, α-D-glucosaminidase EC. 3.2.1.50, β-D-glucosaminidase EC. 3.2.1.30, and β-D-galactosidase EC. 3.2.1.33) were investigated in cells from the affected cat. The activity of a-L-iduronidase was deficient in both cultured fibroblasts and peripheral leucocytes, while the activity of the other enzymes was similar to that in normal cats. It is apparent that the pattern of GAG excretion, evidence of lysosomal storage in various tissues, evidence of defective GAG degradation in cultured fibroblasts, and the specific deficiency in activity of α-L-iduronidase in the affected cat parallel closely the findings in mucopolysaccharidosis (MPS) I of man. Speculation: This feline model of MPS I (Hurler, Scheie, or Hurler/Scheie Syndrome) should allow advances in the understanding of the pathogenesis and approaches to therapy for this and related genetic storage diseases. © 1979 International Pediatric Research Foundation, Inc.