G(M1) gangliosidosis (type 1) in a cat

Abstract

A kitten with clinical and morphological symptoms of a neurovisceral lysosomal-storage disease has been shown to have a marked deficiency of acidic β-D-galactosidase in the brain, kidney and spleen. Chromatography on concanavalin A-Sepharose and inhibition studies with 2,5-dihydroxymethyl-3,4-dihydroxypyrrolidine, a selective inhibitor of the neutral broad-specificity β-D-galactosidase, have shown that the residual β-D-galactosidase at pH 4.0 in the tissues of the affected cat is due to the neutral β-D-galactosidase and that there is a complete deficieny of the acidic (lysosomal) β-D-galactosidase. There is marked accumulation in all tissues and excretion in the urine of neutral oligosaccharides. Analysis of these oligosaccharides by fast-atom-bombardment mass spectrometry and g.l.c. suggests that they arise from the incomplete catabolism of N-glycans of glycoproteins. The ganglioside content of all the tissues is elevated, and it has been shown by t.l.c. that the concentration of a ganglioside fraction with a mobility similar to that of G(M1) ganglioside is particularly increased. There is also some evidence of accumulation of glycosaminoglycans in the brain. The clinical symptoms, the complete deficiency of acidic β-D-galactosidase and the storage products in visceral organs all suggest that this is a case of feline G(M1)-type gangliosidosis comparable with the severe infantile (Type 1) form of the disease in humans.