ADULT-ONSET LYSOSOMAL STORAGE DISEASE IN A SCHIPPERKE DOG - CLINICAL,MORPHOLOGICAL AND BIOCHEMICAL-STUDIES

An adult-onset lysosomal storage disorder was diagnosed in a 5-year-ol d Schipperke dog with progressive cerebellar and central vestibular si gns. It was characterized by cerebellar atrophy with extensive loss of Purkinje and granular cells, and hydrocephalus. Enlarged and vacuolat ed neurons were observed in spinal cord and brain; pancreatic centrolo bular and islet cells were also vacuolated. Ultrastructurally, enlarge d secondary lysosomes laden with lamellated membrane structures were p resent in neurons and empty enlarged vacuoles were found in pancreatic centroacinar, ductal, and islet cells. On frozen sections neurons sta ined with Ricinus communis agglutinin-I and wheat germ agglutinin. On paraffin sections neurons stained with luxol fast blue, periodic acid- Schiff, Concanavalia ensiformis agglutinin, and were autofluorescent. These findings indicate an accumulation of glycolipids containing term inal beta-galactosyl and alpha-sialyl residues, and N-linked oligosacc harides. Tissue activity of lysosomal beta-galactosidase was 50 % of n ormal and the activity of beta-hexosaminidase was elevated. Brain lipi d-bound sialic acid was twice normal, with a small increase of G(M1)-g anglioside, but there was a significant elevation of G(M2) (G(D2)) and G(M3) (G(D3)). In addition, significant elevations of sialylated and non-sialylated oligosaccharides were noted. These clinical, biochemica l and pathological findings are similar to those observed in human pat ients with adult-onset galactosialidosis.