RESUMO
Two adult sisters with severe spinocerebellar degeneration were deficient in hexosaminidase A and B. GM2 ganglioside storage in brain tissue obtained by autopsy from one patient was most pronounced in the cerebellum. Hexosaminidase activity in brain tissue was negligible, but fibroblasts from the second patient contained relatively high amounts of heat-labile activities of both isoenzymes. Pulse-chase experiments showed synthesis of precursor alpha- and beta-chains of hexosaminidase, maturation of the alpha-chain, but only a very small amount of mature beta-chain. These data indicate a destabilizing mutation in the beta-locus. Substrate-specific effects of this mutation were demonstrated by the urinary oligosaccharide pattern.
Assuntos
Encéfalo/metabolismo , Gangliosídeos/metabolismo , Doença de Sandhoff/metabolismo , Degenerações Espinocerebelares/metabolismo , beta-N-Acetil-Hexosaminidases/metabolismo , Adulto , Encéfalo/patologia , Feminino , Fibroblastos/enzimologia , Hexosaminidase A , Humanos , Isoenzimas/metabolismo , Oligossacarídeos/urina , Doença de Sandhoff/classificaçãoRESUMO
Histochemical analysis of frontal and temporal lobes from four patients with Pick presenile dementia indicated intracellular and extracellular deposits of gangliosides. Thin layer chromatography of gangliosides disclosed the presence of an unknown ganglioside, a decrease of N-acetylgalactosamine-GDla and an increase of GTla and/or GD2 in white matter of Pick brain. Chromatography of gray matter and quantitation of the sialic acid content yielded results similar to controls. It is suggested that degradation and removal of gangliosides is incomplete in Pick disease.