GM2 Ganglioisosis (Tay-Sachs and Sandhoff disease) is a rare autosomal recessive disorder that affects an estimated 1-9:100,000 people and are caused by mutations in the HEXA gene, which disrupts the activity of the enzyme beta-hexosaminidase A, preventing the enzyme from breaking down GM2 gangliosides. The enzyme deficiency prevents the normal, stepwise degradation of ganglioside, which accumulates unchecked within the cellular lysosome, particularly in neurons. As a result, individuals with GM2 gangliosidosis experience progressive neurological diseases including motor deficits, progressive weakness and hypotonia, decreased responsiveness, vision deterioration, and seizures.
