Defective HEXA does not cleave the terminal GalNAc from keratan sulfate

Stable Identifier
R-HSA-9035978
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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Beta-hexosaminidase A (HEXA) cleaves the terminal N-acetyl galactosamine (GalNAc) from glucosaminoglycans (GAGs) and any other molecules containing a terminal GalNAc. Defects in the alpha subunits are the cause of GM2-gangliosidosis type 1 (GM2G1; MIM:272800), also known as Tay-Sachs disease (Nakano et al. 1988). The severest form of Tay-Sachs disease, infant-onset, is characterised by neurodegeneration, blindness and death by age 2 or 3. Hexosaminidase activity in this form of the disease is below 10% of normal levels (Okada et al. 1971). The most frequent mutation of infant-onset Tay-Sachs disease of Ashkenazi Jews is a 4-bp insertion in exon 11. This mutation introduces a premature termination signal (p.Y427Ifs*5) resulting in a deficienct mRNA (Myerowitz & Costigan 1988).

More than 100 mutations in HEXA have been identified to date with varying severity of disease. The next most common mutation produces abnormally processed RNA; a G to C transversion at the 5' end of intron 12 (Arpaia et al. 1988, Myerowitz 1988) (not annotated here). This mutation, together with Y427Ifs*5, account for ~97% of the HEXA gene mutations in the Ashkenazi Jewish population (Mahuran 1995).

Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
beta-N-acetylhexosaminidase activity of HEXA Y427Ifs*5 [lysosomal lumen]
Physical Entity
Activity
Normal reaction
Disease
Name Identifier Synonyms
gangliosidosis GM1 3322 GM1 gangliosidosis (disorder), GM>1< gangliosidosis (disorder), beta-Galactosidase deficiency, deficiency of beta-galactosidase (disorder), Beta-galactosidase deficiency, Landing syndrome
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