Tay-Sachs DiseaseTay-Sachs Disease

What is it? What is it? A degenerative neurological disorder where virtual A degenerative neurological disorder where virtual

absence of activity of a lysosomal enzyme, absence of activity of a lysosomal enzyme, hexosaminidase Ahexosaminidase A

BiochemistryBiochemistry Characterized by deficiency of alpha subunit of Characterized by deficiency of alpha subunit of

hexosaminidase Ahexosaminidase A A deficiency of this enzyme results in accumulation of A deficiency of this enzyme results in accumulation of

Gm2 gangliosides in neurons causing a severe neurologic Gm2 gangliosides in neurons causing a severe neurologic degenerative disease resulting in blindness, loss of degenerative disease resulting in blindness, loss of neurologic function, and death between ages 2 and 4 neurologic function, and death between ages 2 and 4 years.years.

Who is affected?Who is affected? 3% of Ashkenazi Jews are carriers of Tay-Sachs disease3% of Ashkenazi Jews are carriers of Tay-Sachs disease Less than 0.3% of the general population are carriers of Less than 0.3% of the general population are carriers of

Tay-SachsTay-Sachs The frequency of matings between two carriers and thus The frequency of matings between two carriers and thus

the risk of having a Tay-Sachs child is 1 in 1,000 in the the risk of having a Tay-Sachs child is 1 in 1,000 in the Ashkenazi Jewish population. Ashkenazi Jewish population.

Whereas, in a non-Ashkenazi Jewish population the Whereas, in a non-Ashkenazi Jewish population the probability is 1 in 360,000.probability is 1 in 360,000.

Why are Ashkenazi Jews Why are Ashkenazi Jews Carriers of Tay-Sachs Carriers of Tay-Sachs

Disease?Disease?

Balanced Polymorphism:Balanced Polymorphism:

One copy of the Tay-Sachs gene protects One copy of the Tay-Sachs gene protects individuals against tuberculosis.individuals against tuberculosis.

TB was prevalent within the Eastern European TB was prevalent within the Eastern European Jewish population, due to living conditions.Jewish population, due to living conditions.

The mortality was so high that the gene pool was The mortality was so high that the gene pool was very small, increasing the risk of carrying the very small, increasing the risk of carrying the Tay-Sachs disease for Ashkenazi Jews.Tay-Sachs disease for Ashkenazi Jews.

***The Tay-Sachs gene increases the risk for ***The Tay-Sachs gene increases the risk for breast cancer and Gaucher’s disease.breast cancer and Gaucher’s disease.

GeneticsGenetics

The inheritance pattern of Tay-Sachs is The inheritance pattern of Tay-Sachs is autosomal recessive.autosomal recessive.

Three mutations account for 98% of Tay-Sachs Three mutations account for 98% of Tay-Sachs disease in Ashkenazi Jews.disease in Ashkenazi Jews.

Therefore, definitive DNA diagnosis is availableTherefore, definitive DNA diagnosis is available

Screening for Tay-SachsScreening for Tay-Sachs The screening for Tay-Sachs disease is a The screening for Tay-Sachs disease is a

controversial issue.controversial issue.

Screening has reduced the incidence of Tay-Sachs Screening has reduced the incidence of Tay-Sachs in the Ashkenazi Jewish population by 95%.in the Ashkenazi Jewish population by 95%.

In the Ashkenazi Jewish population, you can only In the Ashkenazi Jewish population, you can only screen for Tay-Sachs prior to marriage.screen for Tay-Sachs prior to marriage.

Abortions are rare in the Askkenazi Jewish Abortions are rare in the Askkenazi Jewish population.population.

Screening for Tay-Sachs Screening for Tay-Sachs DiseaseDisease

There are several screening techniques available.There are several screening techniques available.

One screening involves an inexpensive test to One screening involves an inexpensive test to measure the heat-labile hexosaminidase activity measure the heat-labile hexosaminidase activity in the blood.in the blood.

Carrier status can be confirmed by definitive Carrier status can be confirmed by definitive measure of hexosaminidase activity in white measure of hexosaminidase activity in white blood cells.blood cells.

Ethical ConsiderationsEthical Considerations The information obtained from genetic screening The information obtained from genetic screening

for Tay-Sachs is only beneficial when the for Tay-Sachs is only beneficial when the information is presented to potential parents in a information is presented to potential parents in a meaningful way.meaningful way.

Misinformation can cause loss of self-esteem by Misinformation can cause loss of self-esteem by carrier and social stigmatization and carrier and social stigmatization and discrimination.discrimination.

Early screenings only effective when it is used in Early screenings only effective when it is used in a reasonable fashion and information is used a reasonable fashion and information is used appropriately by those who are screened.appropriately by those who are screened.