asialo-gm1-ganglioside and Gangliosidoses

The uptake and degradation of GM1 ganglioside (GM1) and asialoGM1 ganglioside (GA1) were studied in cultured fibroblasts from normal individuals and patients with beta-galactosidase deficiency, using the lipid-loading test. The glycolipids were incorporated from the media into the fibroblasts and the terminal galactose was hydrolyzed in normal cells. The hydrolysis rates of GA1 were 80-86% of normal on the 3rd day after loading, while GM1 was hydrolyzed slowly; 35-54% on the 14th day. In infantile GM1 gangliosidosis and I-cell disease, little GM1 and GA1 was hydrolyzed on any day of culture, while fibroblasts from patients with adult GM1 gangliosidosis, Morquio disease type B and galactosialidosis hydrolyzed the lipids at nearly normal rates. The intracellular accumulation of the glycolipids, on the basis of protein content, was abnormally high in the case of infantile GM1 gangliosidosis and I-cell disease, but normal in the other disorders examined. These observations indicate that the in situ metabolism of GM1 and GA1 is probably normal in fibroblasts from patients with adult GM1 gangliosidosis, Morquio disease type B and galactosialidosis, although in vitro beta-galactosidase activities in these disorders are very low. The results are compatible with findings that GM1 and GA1 do not accumulate in the somatic organs of patients with adult GM1 gangliosidosis and galactosialidosis. In I-cell disease, however, the results of the loading test did not agree with the finding that there is little accumulation of glycolipids in postmortem tissues.

Topics: Adult; Animals; beta-Galactosidase; Brain; Cattle; Cells, Cultured; Fibroblasts; G(M1) Ganglioside; Galactosidases; Gangliosidoses; Glycosphingolipids; Humans; Infant; Kinetics; Reference Values; Tritium

Brains of two patients with GM1 gangliosidosis type 1 and type 2, together with the age-matched control brains, were analyzed for glycosphingolipids. Six species of neutral glycolipids, eight species of gangliosides, and sulfatide were isolated from the diseased brains and identified. In addition to GM1 ganglioside and its asialo derivative, the diseased brains accumulated considerable amounts of gangliotriaosylceramide and glycolipids belonging to the globo series, the accumulation of which cannot be explained by deficient beta-galactosidase activity in this disease. GM4 ganglioside was detected in the type 2 brain, but not in type 1. As to fatty acid composition of monohexosylceramides and sulfatide in the two diseased brains, stearic acid was more predominant in the type 1 brain than in the type 2 brain. In light of our previous observations on a Tay-Sachs brain and present results, it appears that metabolism of the globo series glycolipids, which is active in normal brain at early infancy but inactive thereafter, remains in brains with GM1 gangliosidosis (types 1 and 2) and Tay-Sachs disease, reflecting a disturbance in development of the brain.

Topics: beta-Galactosidase; Brain; Carbohydrates; Child; Child, Preschool; Fatty Acids; G(M1) Ganglioside; Gangliosides; Gangliosidoses; Glycolipids; Glycosphingolipids; Humans; Male; Sulfoglycosphingolipids

Topics: Enzyme Activation; G(M1) Ganglioside; Galactosidases; Galactosylceramidase; Gangliosidoses; Glycoproteins; Glycosphingolipids; Humans; Hydrolysis; In Vitro Techniques; Liver; Molecular Weight; Proteins; Saposins; Sphingolipid Activator Proteins