This autosomal recessive lysosomal-storage disease is characterized by absence of the hexosaminidase A enzyme. his leads to accumulation of GM2 gangliosides in the central nervous system, progressive neurodegeneration, and death in early childhood. Afected individuals have almost complete absence of the enzyme, whereas carriers are asymptomatic but have less than 55-percent hexosaminidase A activity. The carrier frequency of T ay-Sachs disease in Jewish individuals of Eastern European (Ashkenazi) descent approximates 1 in 30, but it is much lower, only about 1 in 300, in the general population. Other groups at greater risk for Tay-Sachs disease include those of French-Canadian and Cajun descent. An international Tay-Sachs carrier-screening campaign was initiated in the 1970s and met with unprecedented success in the Ashkenazi Jewish population. he incidence of T ay-Sachs disease subsequently declined more than 90 percent (Kaback, 1993). Most cases of Tay-Sachs disease now occur in nonJewish individuals.
he American College of Obstetricians and Gynecologists (20 17b) has the following screening recommendations for T aySachs disease: 1.
Screening should be ofered before pregnancy if both members of a couple are of Ashkenazi Jewish, French-Canadian, or Cajun descent, or if there is a family history ofTay-Sachs disease.
2.
When only one member of the couple is of one of the above ethnicities, the high-risk partner may be screened first, and if found to be a carrier, the other partner also should be ofered screening. If there is a family history ofTay-Sachs disease, an expanded carrier screening panel may not be the best approach unless the familial mutation is included in the panel.
3.
Molecular testing (DNA-based mutation analysis) is highly efective in Ashkenazi Jewish individuals and other high-risk groups, but the detection rate in low-risk groups is more limited.
4.
Biochemical analysis of the hexosaminidase A serum level has a sensitivity of 98 percent and is the test that should be performed in individuals from low-risk ethnicities. Leukocyte testingmust be used if the woman is already pregnant or taking oral contraceptives.
5.
Ifboth partners are found to be carriers ofTay-Sachs disease, genetic counseling and prenatal diagnosis should be ofered. Hexosaminidase activity may be measured from chorionic villus sampling or amniocentesis specimens.
The carrier rate among individuals of Eastern European (Ashkenazi) Jewish descent approximates 1 in 30 for T ay-Sachs disease, 1 in 40 for Canavan disease, and 1 in 32 for familial dysautonomia. Fortunately, the detection rate of screening tests for each is at least 98 percent in this population. Because of their relatively high prevalence and consistently severe and predictable phenotype, the American College of Obstetricians and Gynecologists (2017b) recommends that carrier screening for these three conditions be ofered to Ashkenazi Jewish individuals, either before conception or during early pregnancy. his is in addition to carrier screening for cystic fibrosis and spinal muscular atrophy, which are ofered to all women who are considering pregnancy or who are currently pregnant. Further, there are several other autosomal recessive conditions for which the College recommends that screening be considered (American College of Obstetricians and Gynecologists, 2017b).