Meta-Biol

• Pathways

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. Beta-hexosaminidase B (HEXB) cleaves the terminal N-acetyl galactosamine (GalNAc) from glucosaminoglycans (GAGs) and any other molecules containing a terminal GalNAc. Defects in the beta subunits are the cause of GM2-gangliosidosis type 2 (GM2G2) (MIM:268800), also known as Sandhoff disease (Banerjee et al. 1991). HEXB mutations can result in either infantile-, juvenile-, adult- or chronic-onset forms of Sandhoff disease, with the infantile form being the most severe. A common HEXB mutation causing the infantile-onset form of Sandhoff disease is a 16kb deletion of the HEXB promoter, exons 1 to 5, and part of intron 5 and accounts for ~27% of Sandhoff alleles examined (not annotated here) (Bikker et al. 1989, Neote et al. 1990). Other, less common mutations causing the infantile form are S62L, R284*, M26Cfs*5 and I322Kfs*5 (Zhang et al. 1995, Zampieri et al. 2009, Drousiotou et al. 2000).