Tay-Sachs Disease n What is it? n A degenerative neurological disorder where virtual absence of activity of a lysosomal enzyme, hexosaminidase A n Biochemistry n Characterized by deficiency of alpha subunit of hexosaminidase A n A deficiency of this enzyme results in accumulation of Gm2 gangliosides in neurons causing a severe neurologic degenerative disease resulting in blindness, loss of neurologic function, and death between ages 2 and 4 years.

Who is affected? n 3% of Ashkenazi Jews are carriers of Tay-Sachs disease n Less than 0.3% of the general population are carriers of Tay- Sachs n The frequency of matings between two carriers and thus the risk of having a Tay-Sachs child is 1 in 1,000 in the Ashkenazi Jewish population. n Whereas, in a non-Ashkenazi Jewish population the probability is 1 in 360,000.

Why are Ashkenazi Jews Carriers of Tay-Sachs Disease? n Balanced Polymorphism: n One copy of the Tay-Sachs gene protects individuals against tuberculosis. n TB was prevalent within the Eastern European Jewish population, due to living conditions. n The mortality was so high that the gene pool was very small, increasing the risk of carrying the Tay-Sachs disease for Ashkenazi Jews. n ***The Tay-Sachs gene increases the risk for breast cancer and Gaucher’s disease.

Genetics n The inheritance pattern of Tay-Sachs is autosomal recessive. n Three mutations account for 98% of Tay-Sachs disease in Ashkenazi Jews. n Therefore, definitive DNA diagnosis is available

Screening for Tay-Sachs n The screening for Tay-Sachs disease is a controversial issue. n Screening has reduced the incidence of Tay-Sachs in the Ashkenazi Jewish population by 95%. n In the Ashkenazi Jewish population, you can only screen for Tay-Sachs prior to marriage. n Abortions are rare in the Askkenazi Jewish population.

Screening for Tay-Sachs Disease n There are several screening techniques available. n One screening involves an inexpensive test to measure the heat-labile hexosaminidase activity in the blood. n Carrier status can be confirmed by definitive measure of hexosaminidase activity in white blood cells.

Ethical Considerations n The information obtained from genetic screening for Tay-Sachs is only beneficial when the information is presented to potential parents in a meaningful way. n Misinformation can cause loss of self-esteem by carrier and social stigmatization and discrimination. n Early screenings only effective when it is used in a reasonable fashion and information is used appropriately by those who are screened.