Variant of GM2-gangliosidosis with hexosaminidase A having a severely changed substrate specificity.
The levels of hexosaminidase A activity in cultivated fibroblasts of two patients with GM2-gangliosidosis were close to the normal range with 4-methylumbelliferyl-beta-D-2-acetamido-2-deoxyglucopyranoside and 4-methylumbelliferyl-beta-D-2-acetamido-2-deoxygalactopyranoside as substrates, and the enzymes were normal in most parameters analyzed. However, the enzymes of both patients were almost completely inactive against two specific substrates for hexosaminidase A, rho-nitrophenyl-6-sulfo-2-acetamido-2-deoxy-beta-D-glucopyranoside, and ganglioside GM2 in the presence of GM2-activator. Fibroblast extracts of both patients showed normal hexosaminidase B and GM2-activator activity, the latter was strongly decreased in two cases with variant AB. It is suggested that human hexosaminidase A may contain two different active sites which might be inactivated separately by different mutations.
D001665:Binding Sites; D002675:Child, Preschool; D005733:Gangliosidoses / Q000201:enzymology* / Q000235:genetics; D054818:Hexosaminidase A; D054819:Hexosaminidase B; D006596:Hexosaminidases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009154:Mutation; D013379:Substrate Specificity; D001619:beta-N-Acetylhexosaminidases
D006596:Hexosaminidases; D054818:Hexosaminidase A; D054819:Hexosaminidase B; D001619:beta-N-Acetylhexosaminidases