Chronic G_M1 gangliosidosis presenting as dystonia: II. Biochemical studies

Abstract

A patient with chronic GM1 gangliosidosis was studied enzymatically and biochemically. Leukocyte acid beta-galactosidase activity was severely deficient. In brain and liver, the 4-methylumbelliferyl beta-galactosidase with acidic pH optimum and lactosylceramidase II were deficient while other hydrolases were present in normal amounts, including sialidase determined with N-acetylneuramin-lactose and fetuin as substrates. Neutral beta-galactosidase in liver was increased up to fourfold over the control. Corresponding to the pathological findings, GM1 ganglioside sialic acid was increased in the basal ganglia to 57% of the total (normal, 12 to 16%), accounting for the rise in total ganglioside to 180% of normal in this origin. Only slight to moderate elevations in the proportion of GM1 ganglioside were noted in the cerebral cortex and white matter, without major increase in total ganglioside. Elevated asialo GM1 ganglioside was also confined to the basal ganglia. There was no increase in hepatic glycoproteins or in keratan sulfate-like materials. This is the only known patient with chronic GM1 gangliosidosis in whom abnormal accumulation of GM1 ganglioside has been demonstrated in affected tissue and sialidase deficiency has been excluded as the primary genetic defect.

Neuropathology of Late Onset Gangliosidoses

“…In the cerebellum, Purkinje cell dendrites showed focal dilatation with stor age materials. Analytical and enzymological studies of the brain of the patient revealed a generalized deficiency of acid p-galactosidase but in agreement with locally accentuated pathology in the basal ganglia, accumula tion of GMi ganglioside and GA] in the basal ganglia was a far greater degree than in other regions of the CNS [16]. A younger brother of this patient, who had the same disease, was also studied postmortem.…”

β-Galactosidase Deficiency

“…In one well-characterized patient, abnormal accumulation of G M1 ganglioside paralleled the distribution of pathologic lesions in that the basal ganglia clearly contained a much larger quantity of G M1 ganglioside than did the cerebral cortex. 12,13 The main storage materials in the systemic organs are heterogeneous galactose-rich fragments of varying molecular weights derived from glycoproteins, keratan sulfate, and other carbohydrate-containing materials. The most insoluble of these was first described as keratin sulfate-like based on its behavior in preparative procedures, its electrophoretic properties, and its sugar composition.…”

Genetic Defects in Glycoprotein Metabolism

“…Intellectual impairment is mild, but a slow, progressive deterioration is apparent (69, 106,235,242,279).…”