[PS13-2A-1] GM2 Gangliosidosis: A Genetic Aspect
GM2 gangliosidosis including Tay-Sachs disease (TSD), Sandhoff disease (SD), and GM2 activator protein deficiency (GM2AP or AB variant) is a group of lysosomal storage disorders, which impairs breakdown of GM2 ganglioside, and leads to its accumulation, particular in neuronal cells. These diseases result from deficiency of -hexosaminidase (HEX), or rarely, defect of activator protein. Two isoforms of HEX include HEX-A (subunit) and HEX-B ( subunit). Mutations of either gene encoding -subunit (HEXA gene), -subunit (HEXB gene), or the activator protein (GM2A gene) cause TSD, SD, and GM2AP, respectively. . Infant with TSD, SD, and GM2AP are clinically indistinguishable, which is characterized by developmental regression, startle response with hyperacusis, seizures, and macular cherry-red spots, leading to death before 3-5 years of age. Mild hepatosplenomegaly is often noted in SD. Juvenile and adult forms present with slow neurological progression. Jewish population has high prevalence of TSD with particular common mutations. There is no prevalence data in each country in Asia. Diagnosis testing includes enzyme activities, along with molecular testing due to pseudodeficiency alleles are concerned. Some common mutations have been published in some ethnic groups such as c.571-1G>T in HEXA from Japan, c.850C>T (p.R284X) in HEXB from India. In Thailand, five infantile SD patients were diagnosed in the past 9 years, interestingly, no TSD. The most common HEXB mutation, c.1652G>A (p.C551Y) (90% of mutant alleles) was found in Thai infantile SD. Although, there is no definite treatment, many clinical trials including gene therapy have been going on. Genetic counseling is recommended.