Diagnosis of subtypes of GM1 gangliosidosis in vitro and in vivo--using urinary oligosaccharides as substrates.

In order to delineate clinical subtypes of GM1 gangliosidosis enzymologically, we prepared galactosyl oligosaccharides from the urine of patients, as substrates, and established the method of the galactosyl oligosaccharide beta-galactosidase assay. Galactosyl oligosaccharides beta-galactosidase activities (nmol/mg protein/20 h) in vitro, using substrates without repeating structures were; type 1, 1.0 +/- 0.5 (n = 6), type 2A, 2.1, type 2B, 3.4 +/- 0.7 (n = 5), type 3, 4.9 +/- 0.2 (n = 2). The activities in vitro using substrates with repeating structures were: type 1, 0.3 +/- 0.2 (n = 5), type 2A, 1.2, type 2B, 2.2 +/- 0.5 (n = 4), type 3, 4.2 +/- 0.3 (n = 2). The activities using substrates with and without repeating structures were affected in the fibroblasts of patients, and the residual activities in each subtype were reduced progressively with the increasing severity of the clinical features. The ratio between activities using substrates without repeating structures and activities using substrates with repeating structures indicated that beta-galactosidase activities toward Gal beta 1- of repeating structures were reduced progressively with the increasing severity of the clinical features. The activities in vivo (pmol/mg protein per 24 h) were: type 1, 11.8 +/- 1.8 (n = 2), type 2A, 24.8, type 2B, 40.0 +/- 9.7 (n = 2), type 3, 63.2. The activities in vivo were affected in the fibroblasts of patients and the residual activities were reduced in proportion to the severity of the clinical features. These differences of residual activities among each subtype make it possible to delineate clinical subtypes enzymologically.