Tay-Sachs Disease

In 1969, a nationwide screening program to identify carriers was initiated in the United States. Patients and carriers can be indentified by a simple blood test that measures Hex-A activity. The results of screening and educational programs were extraordinarily successful. In 1970, the number of children born in the United States with Tay-Sachs disease dropped from 100 to 50; in 1980, the number dropped even further, to 13. Many carriers identified in this screening program opted not to have children. However, carriers could also reduce their risk of having children with the disease if they made sure their potential partners were also tested for carrier status.

A newer, better screening test is now available. Carrier testing involves detection of this protein or enzyme deficiency, the accuracy of which is sometimes affected by pregnancy and other factors. More recently, researchers have developed a genetic test that detects the defective gene in a blood sample. Blood samples can be analyzed for either DNA mutations or enzyme activity. The enzyme assay is a test that measures Hex-A activity with carriers having reduced activity levels than non-carriers, while affected babies have absent enzyme activity levels. This test can be used from any individual from any ethnic background.

In 1989, researchers identified three genetic changes, or mutations, responsible for Tay-Sachs disease. Two of these mutations cause the infantile form of the disease. By testing for the existence of these mutations in a person's blood, carriers are more accurately identified. The test is more specific than the enzyme test and is easier to perform. Over 80 mutations have been identified for the gene that encodes Hex-A. The more prevalent mutations are used for detection, especially mutations that are associated with the later-onset form. However, since all the mutations are not screened, there is a number of carriers that will not test positive. Currently, testing detects about 95% of carriers in the Ashkenazi Jewish populations and about 60% of non-Jewish individuals. This test can assist parents in making reproductive decisions. DNA testing is currently the accepted approach to test individuals of confirmed Ashkenazi Jewish descent, whereas newborn screening programs can use dried blood spots on filter paper to measure Hex-A activity. For prenatal diagnosis, Hex-A levels can be measured in amniotic fluid by a procedure called amniocentesis. As in all genetic testing services, the proper genetic counseling and followup procedures should always accompany any genetic test.