GM2 Gangliosidosis

The gangliosides are glycosphingolipids consisting of ceramide, hexose molecules, sialic acid, and hexosamine, normally present in the plasma membrane of the neurons. Catabolic degradation of GM2 ganglioside to GM3 ganglioside requires two isoenzymes—hexosaminidase A (HexA) and hexosaminidase B (HexB) and an activator protein. HexA consists of an a-subunit and a P-subunit, and HexB consists of two P-subunits (Table 9.3).

The three genetic variants of GM2 gangliosidosis have similar clinical expression.

• Tay-Sachs disease or variant B is caused by mutations in the gene for the a-subunit of hexosaminidase A. The gene (HEXA) maps to chromosome 15.

• Sandhoff disease or variant O is caused by mutations in the gene for the P-subunits of hexosaminidase A and B. The gene (HEX B) maps to chromosome 5.

• Variant AB is caused by mutations in the gene of GM2 activator protein (GM2A), located on chromosome 5.

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