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The Success Story of Gene Tests
After 30 years, the Tay-Sachs screening program has lessons to share
By Julie Buckles

Featured article.

Sex, money and children are the kinds of issues young couples deal with. In his premarital counseling sessions, Rabbi Julian Cook raises another: testing for Tay-Sachs disease.

"It doesn't take up a lot of our conversation," says Cook, of the Central Synagogue of Nassau County in New York. "But because we are a special population, my role is to impress upon Jewish couples of childbearing age the importance of being tested."

In Jewish communities around the world, couples are urged to take the Tay-Sachs blood test before deciding to have children. Now 30 years old, carrier screening for Tay-Sachs is the longest-running, population-based program designed to prevent a lethal genetic disease. Screening has reduced the number of Tay-Sachs cases in the U.S. and Canada by 90 percent.

"This is the major success story in terms of carrier screening programs," says Margaret McGovern, associate professor of Human Genetics at Mount Sinai School of Medicine in New York.

A fatal neurodegenerative disease in all cases, Tay-Sachs mainly affects Jews of Ashkenazi descent. Before 1970, physicians diagnosed at least 60 new cases of Tay-Sachs in the US Jewish population each year. Today, there are fewer than five new cases annually.

In three decades, more than 1.4 million people have been tested.

Experts attribute the success of the Tay-Sachs program to a tightly woven, three-pronged approach of accurate testing, community education and individual counseling.

"Any good program would include all three components of the Tay-Sachs model," says McGovern. Only a few other genetic screening programs exist, all of which operate on a smaller scale. Researchers have successfully duplicated the Tay-Sachs model to test for b-thalassemia in Mediterranean and Asian communities and for aspartyglucosaminuria in parts of Finland.

In the next year or so, most obstetricians in the US are likely to provide information about genetic screening for cystic fibrosis for Caucasians. This would be the largest and most ambitious DNA testing program ever.

Some researchers caution that the Tay-Sachs model may not translate well to complex genetic disorders. Cystic fibrosis, for example, is not fatal in children and varies in severity from person to person. The target community is larger and less defined, and test results are less clear-cut.

"Tay-Sachs families agonize with decisions about pregnancy intervention, but they come to understand that this is a uniformly horrible, fatal disease," says Michael M. Kaback, of the Children's Hospital and Health Center at the University of California, San Diego. He adds that while screening for Tay-Sachs is difficult, "it is about 100 times less difficult than cystic fibrosis will be."

Nonetheless, Kaback says that launching a screening program today is easier than it was 30 years ago, because of public interest in the human genome projects. "This has created a little more fertile soil for genetic-related information," he says.

A study at New York University Medical Center several years ago found that established screening programs could readily incorporate additional tests. When researchers offered 1,000 Ashkenazi Jews the tests for Tay-Sachs, cystic fibrosis, and Gaucher disease, nearly 70 percent chose to be tested for all three diseases.

Tay-Sachs is caused by the absence of a digestive enzyme called hexosaminidase A (hex A), which breaks down lipids found in brain cells. Without the enzyme, fatty waste accumulates in nervous tissues and eventually destroys the nervous system.

In order to develop Tay-Sachs, a baby must inherit a defective hex A gene from each parent. More than 100 hex A mutations are associated with the disease, although most carriers in the Jewish population have one of three mutations.

Babies born with Tay-Sachs appear normal for several months but show signs of disease by about six months. Symptoms include loss of mental function, blindness, paralysis, and epileptic seizures. The child usually dies by age 3.

Tay-Sachs Disease heterozygote screening 1971-1999

Country Tested (N) Carriers (n) At-risk couples (n)
United States
South Africa
South America

"Overnight, parents go from thinking they have a healthy baby to being handed a death sentence," says Barbara Hanson, an associate professor of biology at Canisius College in Buffalo, New York. Hanson specializes in the history of disease inheritance in Jewish populations.

Tay-Sachs has been reported in children of all races and ethnic backgrounds, but the most affected populations are Ashkenazi Jews, French-Canadians, and Louisiana Cajuns. In these groups, one person in 27 is a carrier. In the general population, the ratio is one in 250. As there is no treatment, the best way to avoid Tay-Sachs is to test potential parents.

Researchers identified the underlying biochemical defect in Tay-Sachs in 1969. The following year a relatively simple and accurate serum test was developed to identify carriers of the mutated gene and a pilot screening-program was launched in Baltimore, Maryland.

The program's developers involved community leaders, medical practitioners, and religious advisers from the start, using their advice and influence to build participation. In three decades, more than 1.4 million people have been tested.

Today's screening program is similar to the pilot study 30 years ago. Gatekeepers of the Jewish community, like Rabbi Cook, provide information about the disease and testing to the target population. Physicians test and counsel individuals, informing them of the prenatal monitoring of pregnancies. The monitoring helps at-risk couples decide whether to abort an affected fetus.

Knowing the risks before conception, couples can decide to adopt or to conceive using artificial insemination techniques or a donated egg. Or they can take their chances (two carriers have a 25 percent chance of producing a baby with Tay-Sachs). For single individuals, the test can guide marriage or mating decisions. Some traditional Orthodox communities screen children and use the information when matching marriage partners.

In the last 30 years, physicians have monitored 3,200 at-risk pregnancies and diagnosed 628 affected fetuses. All but 19 of the affected pregnancies were aborted. Kaback emphasizes another statistic: These families have produced more than 2,550 children unaffected by Tay-Sachs, a result that contrasts starkly to the outcomes prior to carrier screening and prenatal diagnosis.

See related GNN article
»Test Case for Genetic Testing

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Kaback, M.M. Population-based genetic screening for reproductive counseling: the Tay-Sachs disease model. Eur J Pediatr 159, S192-S195 (December 2000).
Kronn, D. et al. Carrier screening for cystic fibrosis, Gaucher disease, and Tay-Sachs disease in the Ashkenazi Jewish population: the first 1000 cases at New York University Medical Center, New York, NY. Arch Intern Med 158, 777-781 (April 13, 1998).
Kaback, M.M. et al. Tay-Sachs disease—carrier screening, prenatal diagnosis, and the molecular era. An international perspective, 1970 to 1993. JAMA 270, 2307-2315 (November 17, 1993).

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