title: Composition of gangliosides and neutral glycosphingolipids of brain in classical Tay-Sachs and Sandhoff disease: more lyso-GM2 in Sandhoff disease?
abstract: The ganglioside composition of the brain from an individual with classical Tay-Sachs disease and from an individual with Sandhoff disease was examined using our new quantitative methods for ganglioside content determination and compared with that of age-matched control brains. The concentration of GM2 was found to be 12.2 and 13.0 mumol/g of fresh tissue in Tay-Sachs disease and in Sandhoff disease cerebral gray matter, respectively. GM2 was 86 and 87% respectively, of total gangliosides. The concentration of GM1 and, in particular, GM3 ganglioside was also found to be increased, whereas the concentration of the major di- and trisialogangliosides (GD1a, GD1b, and GT1b) had diminished markedly. There was no significant increase in level of any other ganglioside than lyso-GM2. Its concentration was 12 and 16 nmol/g in cerebral gray matter of two Tay-Sachs disease brains and 43 nmol/g in Sandhoff disease brain. The Sandhoff disease brain also differed from the classical Tay-Sachs disease brain by having a much higher concentration of gangliotriaosylceramide and globotetraosylceramide. The structures of relevant gangliosides and neutral glycolipids were established by fast atom bombardment-mass spectrometry and permethylation studies.
mesh_terms: D001923:Brain Chemistry; D002675:Child, Preschool; D002855:Chromatography, Thin Layer; D005260:Female; D005333:Fetus / Q000032:analysis; D005678:G(M2) Ganglioside / Q000031:analogs & derivatives / Q000032:analysis; D005732:Gangliosides / Q000032:analysis*; D006028:Glycosphingolipids / Q000032:analysis*; D006801:Humans; D007790:Lactosylceramides / Q000032:analysis; D008297:Male; D013058:Mass Spectrometry; D012497:Sandhoff Disease / Q000378:metabolism*; D013661:Tay-Sachs Disease / Q000378:metabolism*
chemical_list: D005732:Gangliosides; D006028:Glycosphingolipids; D007790:Lactosylceramides; C048941:lysoganglioside G(M2); D005678:G(M2) Ganglioside; C025575:lactotriaosylceramide