Molecular genetics of GM₁β‐galactosidase

The molecular genetics of GM1β‐galactosidase is reviewed. This enzyme exists in two forms, A and B. Form A is monomeric with a molecular weight of 72,000 and appears to be coded by a single autosomal locus. Form B is polymeric and cross‐reacts with anti‐A antibodies; it is coded wholly or in part by the same locus that codes for A. The simultaneous loss of A and B in GM1 gangliosidosis is explained. None of the other β‐galactosidases, including neutral β‐galactosidase, ceramide lactoside β‐galactosidase or cerebroside β‐galactosidase cross‐react with anti‐A antibodies, demonstrating that they are coded by loci separate from A. GM1, β‐galactosidase A is heterocatalytic, cleaving β‐Dgalactose from ganglioside GM1, lactose, N‐acetyllactosamine, and galactose‐containing glycoproteins such as asialofetuin, red cell stromal glycoproteins and keratan sulfate. The pleotropic effects of a single mutation affecting the locus for β‐galactosidase A can be explained by a one gene: one polypeptide: many substrates model. Phenotypic variability among β‐galactosidase A mutants may result from better residual activity of the mutant enzyme for one substrate than for another. Patients with normal int