Hexosaminidase Deficiency

Hexosaminidas degrades GM2 to GM3 ganglioside. The enzyme exists in three isoforms, Hex A, Hex B, and Hex S. Mutations of the gene encoding the α subunit cause Hex A and S deficiency, whereas mutations of the β subunit cause combined Hex A and B deficiency. Tay-Sachs disease, the classic, rapidly progressive infantile form of GM2 gangliosidosis, results from Hex A deficiency; Sandhoff's disease, indistinguishable from Tay-Sachs except for variable organomegaly, results from Hex A and B deficiency. Activator protein deficiency can produce similar phenotypes; less marked deficiencies of Hex A can present as slowly progressive disorders in later life.