Defective HEXA causes GM2G1 (Hyaluronan metabolism)

Beta-hexosaminidase (HEX) cleaves the terminal N-acetyl galactosamine (GalNAc) from glycosaminoglycans (GAGs) and any other molecules containing a terminal GalNAc. There are two forms of HEX; HEXA and B. The A form is a trimer of the subunits alpha, beta A and beta B. The B form is a tetramer of 2 beta A and 2 beta B subunits. Defects in the two subunits cause lysosomal storage diseases marked by the accumulation of GM2 gangliosides in neuronal cells. Defects in the alpha subunits are the cause of GM2-gangliosidosis type 1 (GM2G1) (MIM:272800), also known as Tay-Sachs disease. Classical Tay-Sachs disease is characterised by infant-onset neurodegeneration followed by paralysis, dementia and blindness, Death occurs by the age of 2 or 3. The two other forms of Tay-Sachs disease, juvenile- and adult-onset, are less commom and severe than the infant-onset form.

Summary from Reactome (R-HSA-3656234), read 2026-09-23.