Contributor: Gordon K. Klintworth
GM2 activator deficiency (hexosaminidase activator deficiency, GM2-gangliosidosis variant AB) is a gangliosidosis caused by a severe deficiency of GM2 activator. GM2-gangliosides accumulate as in the disorders caused by mutations in HEXA (Tay-Sachs disease) and HEXB (Sandhoff disease). The clinical manifestations in the few studied cases appear to be  identical to those in Tay-Sachs disease and Sandhoff disease, but the cherry-red spot at the macula has not been recorded. A progressive neurologic disease begins in infancy and is characterized by muscular weakness, hypotonia, myoclonus, a startle reaction and psychomotor retardation. This variant of GM2-gangliosidosis  is extremely rare and very few cases are known. The designation GM2-gangliosidosis variant AB is based on the fact that both hexosaminidase A and hexosaminidase B are present in increased amounts.