Biology 103
2002 First Paper
On Serendip

When a couple has a baby, they pray that they will have an easy childbirth and a healthy newborn. However, an easy delivery and a healthy-seeming baby does not guarantee a problem-free childhood. Children born with Tay-Sachs Disease (TSD), a fatal genetic disorder, do not show symptoms until they are six months old, but almost never survive past the age of five.

Tay-Sachs Disease was named for Warren Tay and Bernard Sachs, two doctors working independently. In 1881, Dr. Tay, an ophthalmologist, described a patient with a cherry red spot on the back of his eye; the presence of this red spot has become a clear signal for the diagnosis of TSD. Several years later, Dr. Sachs, a New York neurologist, described the cellular changes caused by TSD, observed the hereditary nature of the disease, and noted its predominance among Jews of Eastern European descent (1).

A rarer form of the disease known as Late-Onset Tay-Sachs exists, but this paper will focus on classic infantile TSD and explore its scientific and social implications.


Definition and symptoms.

TSD is defined as a genetic disorder that causes the progressive destruction of the central nervous system (2). TSD occurs in babies with the Tay-Sachs gene on chromosome 15 (1). All affected babies exhibit a red spot in the back of their eyes. TSD is caused by the absence of hexosaminidase A (Hex-A), an enzyme whose presence is necessary for the breaking down of acidic fatty materials known as gangliosides. In an unaffected child, gangliosides are made and quickly biodegraded as the brain develops. When a child is afflicted with TSD, ganglioside GM2 accumulates in the brain, distending cerebral nerve cells and forcing physical and mental deterioration (3).

Once the symptoms begin, they grow progressively worse. First, normal development slows, stops, and eventually reverses. Often the baby loses newly-acquired skills such as the ability to crawl, roll over, and interact with its environment. Second, the baby loses peripheral vision and exhibits an "abnormal startle response." Third, general mental function becomes clearly debilitated, and the baby experiences recurrent seizures. Often, children lose coordination, ability to swallow, and respiratory ease. Ultimately, the child becomes blind, deaf, paralyzed, mentally retarded, and completely unable to interact with or respond to his/her environment (1).


Risk factor.

Tay-Sachs Disease is considered extremely rare among the general population. Occurrences of TSD are not limited to, but definitely concentrated in, certain ethnic sub-populations. TSD is often considered a "Jewish disease," but French-Canadians who live near the St. Lawrence River and the Cajun population of Louisiana are also at high-risk. Still, most research on the groups affected most by TSD focuses on American Ashkenazi Jews. The frequency of TSD within the Jewish population is attributed to the "founder effect" in which "genetic disorders and mutations within a closely knit minority group are perpetuated over generations" (4).

The statistics on the frequency of TSD among Jews is startling. TSD potentially affects one in every 2,500 Ashkenazi Jewish newborns (5). Ashkenazi Jews are one hundred times more likely to have an affected child. Only about one in three hundred in the general population (non-Jews and Sephardic Jews) are carriers of the TSD gene, compared to approximately one in thirty Ashkenazi Jews (6). Most people who are carriers are completely unaware since they are perfectly healthy. The gene for Tay-Sachs can be passed down through many generations before anyone in the family line gives birth to a TSD-afflicted baby. If both parents are carriers, the baby has a fifty percent chance of being a carrier, and only a twenty-five percent chance of being born with TSD. There is a twenty-five percent chance that the child of two carriers will be completely unaffected. If only one parent is a carrier, their child has a fifty percent chance of being a carrier and a fifty percent chance of being completely unaffected. A baby can only be born with TSD if both parents are carriers (7). Due to its recessive hereditary characteristics, TSD is classified as autosomal recessive (8).


Prevention and detection.

While there is no cure or proven treatment for TSD, it is a "preventable tragedy" (9). First, it is now recommended that couples within high-risk populations get tested to see whether or not they are carriers. This involves only a simple blood test whose results can be interpreted using either enzyme assay (checks the amount of Hex-A in the bloodstream) or DNA analysis (checks for one of fifty known mutations in the Hex-A gene) (9). Once carrier status is determined, a couple may decide to pursue parenthood at their own discretion, baring in mind that even when both parents are carriers, their child still will have a seventy-five percent chance of being perfectly healthy.

Once the mother is pregnant, she has two options for prenatal diagnosis. The first, amniocentesis, involves removing a small amount of amniotic fluid during the sixteenth week of pregnancy (10). If there is an absence of Hex-A in the fluid, the fetus is affected by TSD, and the couple can choose to have a therapeutic abortion. Another, newer option is chorionic villus sampling (CVS), which is performed during the tenth week of pregnancy (11). This procedure involves removing a small amount of placenta, and test results are returned more quickly than with amniocentesis. Also, should the couple choose to have an abortion, CVS allows them more privacy and safer pregnancy termination (9). Genetic counseling is widely recommended to all couples who are members of high-risk populations, especially those who are determined carriers.


Social and sociological implications.

It is important to analyze the effects of Tay-Sachs Disease from a broader cultural perspective. Because TSD occurs mainly in clearly-defined populations, and also because of the profound moral issues raised by genetic screening, screening-based abortions, and alleged eugenics, a purely scientific study of the disease would be lacking.

A group called Dor Yeshorim (Hebrew for "the generation of the righteous") provides an illuminating example of how the effects of TSD raise moral, social, and even theological issues. Dor Yeshorim was founded in 1983 by groups of Orthodox Jews (led by Rabbi Joseph Eckstein, father of four children born with TSD) in New York and Israel. Rabbi Eckstein intended to do everything within his power to eliminate Tay-Sachs disease from the Jewish population. Through programs implemented by Dor Yeshorim, Orthodox Jewish high schoolers are tested to determine whether or not they are carriers. Rather than receiving the results directly (in an effort to curb stigmatization), they receive a six-digit identification number. Then, when two youths are considering marriage or even dating, they are encouraged to call a hotline. They enter their six-digit numbers, and the service deems them "compatible" or "incompatible" (if both are carriers). Eight thousand people were tested in 1993, and eighty-seven couples who were previously considering marriage decided against it based on their genetic incompatibility (12). A few years later, Dor Yeshorim expanded its testing services to Yeshiva University, sparking controversy. Originally, Dor Yeshorim was aimed at a the Chasidic population, who still arrange marriages; however, arranged marriages are extremely rare at Yeshiva University, and thus the appropriateness of the testing was questioned there (13). Whether or not Dor Yeshorim is morally sound, their tactics have been effective; in 1995, they released a statement which declared: "Today, with continual testing, new cases of Tay-Sachs have been virtually eliminated from our community" (14).


Conclusion.

While Dor Yeshorim's position is a radical one, drastic steps must be taken to put an end to the devastation suffered by families who must cope with the hopeless misery of Tay-Sachs. There is still no cure, and no effective method of treatment. Research is being conducted that utilizes gene therapy to try to repair the mutated Tay-Sachs gene, but attempts have been largely unsuccessful (15). For now, carrier screening and prenatal testing are encouraged for all couples who may be at risk. TSD can also occur in babies who are not born to couples in high-risk populations, so testing and education must be expanded to put an end to Tay-Sachs disease for good.