Tay-sachs disease

Tay-Sachs disease is a fatal genetic disorder that results in progressive destruction of the nervous system.

What Do We Know About Heredity and Tay-Sachs Disease?

Tay-Sachs disease (TSD) is a fatal genetic disorder, most commonly occurring in children, that results in progressive destruction of the nervous system. Tay-Sachs is caused by the absence of a vital enzyme called hexosaminidase-A (Hex-A). Without Hex-A, a fatty substance, or lipid, called GM2 ganglioside accumulates abnormally in cells, especially in the nerve cells of the brain. This ongoing accumulation causes progressive damage to the cells.

In children, the destructive process begins in the fetus early in pregnancy. However, a baby with Tay-Sachs disease appears normal until about six months of age when its development slows. By about two years of age, most children experience recurrent seizures and diminishing mental function. The infant gradually regresses, and is eventually unable to crawl, turn over, sit or reach out. Eventually, the child becomes blind, cognitively impaired, paralyzed and non-responsive. By the time a child with Tay-Sachs is three or four years old, the nervous system is so badly affected that death usually results by age five.

A much rarer form of Tay-Sachs, Late-Onset Tay-Sachs disease, affects adults and causes neurological and intellectual impairment. Only recently identified, the disease has not been extensively described. As for the childhood form of Tay-Sachs, there is no cure. Treatment involves managing the symptoms of the disease.

Defect in Hex-A Gene Causes Tay-Sachs:

Tay-Sachs disease results from defects in a gene on chromosome 15 that codes for production of the enzyme Hex-A. We all have two copies of this gene. If either or both Hex-A genes are active, the body produces enough of the enzyme to prevent the abnormal build-up of the GM2 ganglioside lipid. Carriers of Tay-Sachs - people who have one copy of the inactive gene along with one copy of the active gene - are healthy. They do not have Tay-Sachs disease but they may pass on the faulty gene to their children.

Carriers have a 50 percent chance of passing on the defective gene to their children. A child who inherits one inactive gene is a Tay-Sachs carrier like the parent. If both parents are carriers and their child inherits the defective Hex-A gene from each of them, the child will have Tay-Sachs disease. When both parents are carriers of the defective Tay-Sachs gene, each child has a 25 percent chance of having Tay-Sachs disease and a 50 percent chance of being a carrier.

Eastern European (Ashkenazi) Jews at Greater Risk for Tay-Sachs Disease:

While anyone can be a carrier of Tay-Sachs, the incidence of the disease is significantly higher among people of eastern European (Ashkenazi) Jewish descent. Approximately one in every 27 Jews in the United States is a carrier of the Tay-Sachs disease gene. Non-Jewish French Canadians living near the St. Lawrence River and in the Cajun community of Louisiana also have a higher incidence of Tay-Sachs. For the general population, about one in 250 people are carriers.

There is no cure or effective treatment for Tay-Sachs disease. However, researchers are pursuing several approaches to finding a cure. Scientists are exploring enzyme replacement therapy to provide the Hex-A that is lacking in babies with Tay-Sachs. Bone marrow transplantation has been attempted also, but to date has not been successful in reversing or slowing damage to the central nervous system in babies with Tay-Sachs. Another avenue of research is gene therapy in which scientists transfer a normal gene into cells to replace an abnormal gene. This approach holds great promise for future Tay-Sachs patients.

Is there a test for Tay-Sachs disease?

A simple blood test can identify Tay-Sachs carriers. Blood samples can be analyzed by either enzyme assay or DNA studies. The enzyme assay is a biochemical test that measures the level of Hex-A in a person's blood. Carriers have less Hex-A in their body fluid and cells than non-carriers.

DNA-based carrier testing looks for specific mutations or changes in the gene that codes for Hex-A. Since 1985, when the Hex-A gene was isolated, more than 50 different mutations in this gene have been identified. Nevertheless, some mutations are not yet known. The current tests detect about 95 percent of carriers of Ashkenazi Jewish background and about 60 percent of carriers in the general population.

If both parents are carriers, they may want to consult with a genetic counselor for help in deciding whether to conceive or whether to have a fetus tested for Tay-Sachs. Extensive carrier testing of Ashkenazi Jews has significantly reduced the number of Tay-Sachs children in this population group. Today most cases of Tay-Sachs disease occur in populations thought not to be at high risk.

Prenatal testing for Tay-Sachs can be performed around the 11th week of pregnancy using chorionic villi sampling (CVS). This involves removing a tiny piece of the placenta. Alternatively, the fetus can be tested with amniocentesis around the 16th week of pregnancy. In this procedure, a needle is used to remove and test a sample of the fluid surrounding the baby.

Assisted reproductive therapy is an option for carrier couples who don't want to risk giving birth to a child with Tay-Sachs. This new technique used in conjunction with in-vitro fertilization enables parents who are Tay-Sachs carriers to give birth to healthy babies. Embryos created in-vitro are tested for Tay-Sachs genetic mutations before being implanted into the mother, allowing only healthy embryos to be selected.

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