Lysosomes are membrane-bound organelles which contain hydrolases that degrade unneeded proteins and infectious bacteria. When these substrates accumulate without degradation inside the lysosome, the cells die lysosomal storage diseases (a subset of enzymopathies ensue. Affected tissues grow noticeably large, and mental dysfunction occurs in diseased brains. Tay-Sachs disease is a group of disorders where hexosaminidase A (hexA) cannot degrade the sphingolipid GM2 ganglioside. Since GM2 ganglioside synthesis is most prevalent in the brain, it is most severely affected by Tay-Sachs.
Normal hexA consists of α and β subunits (encoded by HEXA and HEXB) that associates with an activator protein to cleave GM2 ganglioside. Disruption of the α subunit leads to Tay-Sachs disease; disruption of the β subunit o the activator protein leads to, respectively, Sandhoff disease and activator protein deficiency. Tay-Sachs homozygotes are clinically normal at first, but mentally deteriorate by 3-6 months of age and die by 2-4 years. HEXA alleles with some residual activity can lead to late onset, motor dysfunction, psychosis or sometimes no disease at all.