Heritable lysosomal storage disorder with ganglioside accumulation leading to severe neurologic impairment with premature death. Tay-Sachs disease (TSD) and its variants are caused by absence or defects of the alpha subunit of hexosaminidase A.
Synonyms and Classification
GM2 Gangliosidosis B Variant: Tay-Sachs Disease (TSD; Hexosaminidase A Deficiency [Hex A Deficiency]; Pseudo AB Variant): Three types of TSD are described (infantile, juvenile, and adult, which is characterized by a pseudodeficiency mutation in one or both HEXA alleles).
GM2 Gangliosidosis B1 Variant
GM2 Gangliosidosis AB Variant (Hexosaminidase Activator Deficiency): Caused by absence or defects of the hexosaminidase activator. It represents a deficiency of sphingolipid activator protein GM2 required for in vivo degradation of GM2 ganglioside by beta-hexosaminidase A.
GM2 Gangliosidosis O Variant: Sandhoff disease and its variants: Caused by absence or defects of the beta subunit of hexosaminidase A and the subunits of hexosaminidase B. It is also known as SD (Sandhoff Disease), Hex A and Hex B deficiency, or GM2 gangliosidosis, O variant, and it includes the juvenile subacute type.
Incidence in the general US population is 1:320,000 live births and only 1 in 283 persons is a heterozygous unaffected carrier of a HEXA mutation. However, in the Ashkenazi Jewish population, the incidence of affected individuals is 1:2,500 to 3,600 newborns. The carrier of the HEXA mutations in this subgroup of population is 1 in 30 individuals. In certain isolated populations, such as Louisiana Cajuns and Pennsylvania Dutch, the incidence of this disease appears even higher than in individuals of Ashkenazi Jewish descent. The incidence of Sandhoff disease in the United States is estimated to be 1:309,000 non-Jewish newborns. One in 278 persons of non-Jewish descent is a heterozygous unaffected carrier of a HEXB mutation. Approximately 1:1,000,000 Jewish newborns is affected. Individuals affected with the hexosaminidase activator deficiency are very rare. Internationally, the incidence for TSD is estimated at 1:360,000 live births in the general population, and 1:300 individuals are a carrier of the HEXA mutation. Increased frequencies have been reported in Moroccan Jews and some isolated populations in Switzerland and Japan. The incidence in French Canadians living along the border of the eastern St. Lawrence River in the Province of Quebec is similar to the incidence reported for those of Ashkenazi Jewish descent. The international incidence for Sandhoff disease is approximately 1:310,000 non-Jewish newborns. Increased incidences have been suggested in Creoles of northern Argentina, Metis Indians of northern Saskatchewan in Canada, Lebanese, and Hispanics of Mexican or Central American heritage. The mortality associated with this medical condition depends on the type. The classic infantile form usually is fatal by 2 to 4 years of age. In the late infantile subacute, B1 variant form, disease progression is particularly aggressive, leading to death within 2 to 4 years of disease onset. In the juvenile subacute form, death occurs by 10 ...