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.
- 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) is
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 are
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
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 1:2500-3600 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 is 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 to 15 years of age. It usually is
caused by infection and most often ...