Chronic GM1 gangliosidosis presenting as dystonia: II. Biochemical studies.

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.