Gangliosidosis structure

Compound 12 is a tetra-antennary oligosaccharide that was isolated from the urine of a patient with GM,-gangliosidosis.52,64 64a This structure can be conceived of as an extension of the tri- (compound 10) or tri -antennary (compound 11) oligosaccharide with an N-acetyllactos-amine unit. The 500-MHz, H-n.m.r. spectrum of 12 is presented in Fig. 12, and its n.m.r. data are given in Table IV. 

Gm2 gangliosidosis is caused by a deficiency of hexosamidase A and B. It was described for the first time by K.. Sandhoff et al. as Sandhoffs disease in 1968. This biochemical variant (type II) largely corresponds to Tay-Sachs disease, which is also autosomal recessive. Renal globoside (ceramide trihexoside) is stored in the visceral organs, particularly in the liver and spleen. Hepatomegaly is present, occasionally with splenomegaly. The lysosomes within the hepatocytes become considerably larger until they are as big as the nucleus and show lamellar structures. 

Tay-Sachs disease is caused by the mutation of the alpha subunit of hexosaminidase A gene (HEXA). Deficitated hexosaminidases A and B produce 3 distinct clinical forms of ganglioside GM2 storage disease-Tay-Sachs disease, Sandhoff disease, and juvenile GM2-gangliosidosis. Hexosaminidase-A has a structure comprised of alpha-beta subunits and Tay-Sachs disease is the alpha-minus mutation, whereas Sandhoff disease is a beta-minus mutation (Beutler and Kuhl, 1975 Beutler et al., 1975). Subunit alpha is mapped to chromosome 15 (and beta to chromosome 5). Different levels of residual activities are correlated with the age of clinical onset Tay-Sachs disease, 0.1% of normal hexosaminidase late infantile,... 

T12. Tsay, G. C., and Dawson, G., Structure of the keratosulfate-like material in liver from a patient with Gui-gangliosidosis (jS-n-galactosidase deficiency). Biochem. Biophys. Res. Commun. 52, 759-766 (1973). 

Strecker, G. Herlant-Peers, M.C. Foumet, B. Montreuil, J. Structure of Seven Oligosaccharides Excreted in the Urine of a Patient with Sandhoff s Disease (Gm2 Gangliosidosis-Varient O). Eur. J. Biochem. 1977, 81, 165-171. 

Warner, T.G. O Brien, J.S. Structure Analysis of the Major Oligosaccharides Accumulating in Canine Gmi Gangliosidosis Liver. J. Biol Ghent. 1992, 10, 224-242. 

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