Introduction and Clinical Features
Tay-Sachs disease is an incurable, autosomal recessive metabolic disease with increased frequency in certain genetic isolates. The disease is a neurological degenerative disorder that develops when a child is about 6 months old.
Affected children become blind and regress mentally and physically. The disease is fatal in early childhood primarily in newborns of Ashkenazi (Eastern European) Jewish descent.
Among Ashkenazi Jews in North America, for example, Tay-Sachs disease (TSD) is 100 times more frequent (1 in 3600) than in other groups of European ancestry.
This increased disease frequency is because the Tay-Sachs carrier frequency among Askenazi Jews (approximately 1 in 30 Ashkenazi Jews are carriers Opens in new window [heterozygous]) is 10-fold higher than in similar non-Ashkenazi European populations.
Incidence of TSD is also notable in Sephardic Jews and non-Jewish French Canadians living near the St. Lawrence River and in the Cajun community of Louisiana (National Tay-Sachs and Allied Diseases Association, 2006).
When the mutant alleles Opens in new window causing a recessive disease are relatively frequent in a particular population, unrelated spouses have a reasonable chance of both being heterozygous, and therefore consanguinity Opens in new window is generally not a striking feature in the families with affected children.
For example, among Ashkenazi Jews, the parents of children with Tay-Sachs disease are usually not closely related.
When the mutant allele Opens in new window is rare, however, the frequency of carriers is very low and consanguinity is often the explanation for how both members of a couple came to be heterozygous. For example, consanguinity is often present in the parents of Tay-Sachs patients in the population of French ancestry in Quebec, Canada, where mutant alleles for Tay-Sachs diseases are rare.
Patients with Tay-Sachs disease exhibit a deficiency of the β-hexosaminidase enzyme, normally responsible for decomposing the naturally occurring fatty substance GM2-ganglioside.
Toxic buildup of GM2-ganglioside affects the cells of the nervous system. Symptoms include progressive deterioration of both motor and mental function, with diminished vision. They generally manifest at 4 to 6 months of age, with death occurring at 3 to 4 years.
To determine carrier status, clinicians measure hexosaminidase activity in plasma or white blood cells; they also may use gene mutation analysis. Prenatal diagnosis by chorionic villi sampling or amniocentesis can identify couples at risk. Available counseling can help couples identify options for having unaffected children.
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