<unk>  is caused by insufficient activity of the enzyme hexosaminidase A. Hexosaminidase A is a vital hydrolytic enzyme, found in the lysosomes, that breaks down sphingolipids. When hexosaminidase A is no longer functioning properly, the lipids accumulate in the brain and interfere with normal biological processes. Hexosaminidase A specifically breaks down fatty acid derivatives called gangliosides; these are made and biodegraded rapidly in early life as the brain develops. Patients with and carriers of<unk><unk><unk>  can be identified by a simple blood test that measures hexosaminidase A activity. The hydrolysis of GM2-ganglioside requires three proteins. Two of them are subunits of hexosaminidase A; the third is a small glycolipid transport protein, the GM2 activator protein (GM2A), which acts as a substrate-specific cofactor for the enzyme. Deficiency in any one of these proteins leads to ganglioside storage, primarily in the lysosomes of neurons.<unk>  (along with AB-variant GM2-gangliosidosis and Sandhoff disease) occurs because a mutation inherited from both parents deactivates or inhibits this process. Most<unk><unk><unk>  mutations probably do not directly affect protein functional elements (e.g., the active site). Instead, they cause incorrect folding (disrupting function) or disable intracellular transport.
Tay–Sachs disease
Sandhoff disease
Fox–Fordyce disease
Leigh syndrome
Bietti's crystalline dystrophy
Neuronal ceroid lipofuscinosis
Akureyri disease
Dejerine–Sottas disease