Ganglioside storage, hexosaminidase lability, and urinary oligosaccharides in adult Sandhoff's disease.

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.