AB variant of infantile Gm2 gangliosidosis. Deficiency of a factor necessary for stimulation of hexosaminidase A-catalyzed degradation of ganglioside Gm2 and glycolipid Ga2

Abstract

Human kidney extracts heated to 60° and devoid of hexosaminidase activity (2-acetamido-2-deoxy-β-D-glucoside acetamidodeoxyglucohydrolase EC 3.2.1.30) stimulate more than 20-fold the hexosaminidase A-catalyzed degradation of ganglioside G(M2) and glycolipid G(A2), the neuronal storage compounds of G(M2) gangliosidosis. The stimulating factor of this extract, which is labile at temperatures above 60°, is also present in kidney extracts from patients with infantile G(M2) gangliosidosis having a deficiency of hexosaminidase A (Tay-Sachs disease, variant B) and a deficiency of hexosaminidases A and B (variant O). Evidence is presented that this factor is defective in the AB-variant of infantile G(M2) gangliosidosis which is characterized by an accumulation of glycolipids G(M2) and G(A2) despite the fact that the degrading enzymes, hexosaminidases A and B, retain normal activity levels. Thus, variant AB is an example of a fatal lipid storage disease that is caused not by a defect of degrading enzyme but rather by a defective factor necessary for the interaction of lipid substrates and the water-soluble hydrolase.