Definition:

GM2 gangliosidoses are a group of autosomal recessive lysosomal storage disorders caused by deficiency of beta-hexosaminiase or the noncatalytic GM2 activator in glycosphingolipid catabolism. The enzymatic defect results in the accumulation of GM2 ganglioside in neurons that mainly affects motor and spinocerebellar function. Mutations of the HEXA gene cause deficiency of the beta-hexosaminidase A and result in Tay-Sachs disease. Mutations of the HEXB gene, encoding the beta-subunit, cause deficiency of both enzymes (beta-hexosaminidase A and B), leading to Sandhoff disease. Deficiency of the GM2 activator protein, which mediates the interaction between the water-soluble beta-hexosaminidase A and GM2 ganglioside, causes the AB variant of GM2 gangliosidosis.