Adult-onset lysosomal storage disease in a Schipperke dog: clinical,morphological and biochemical studies

Summary An adult-onset lysosomal storage disorder was diagnosed in a 5-year-old Schipperke dog with progressive cerebellar and central vestibular signs. It was characterized by cerebellar atrophy with extensive loss of Purkinje and granular cells, and hydrocephalus. Enlarged and vacuolated neurons were observed in spinal cord and brain; pancreatic centrolobular and islet cells were also vacuolated. Ultrastructurally, enlarged secondary lysosomes laden with lamellated membrane structures were present in neurons and empty enlarged vacuoles were found in pancreatic centroacinar, ductal, and islet cells. On frozen sections neurons stained 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 terminal -galactosyl and -sialyl residues, and N-linked oligosaccharides. Tissue activity of lysosomal -galactosidase was 50% of normal and the activity of -hexosaminidase was elevated. Brain lipid-bound sialic acid was twice normal, with a small increase of G_M1-ganglioside, 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, biochemical and pathological findings are similar to those observed in human patients with adult-onset galactosialidosis.