Quick Reference and Fact Sheets   Tay-Sachs Disease What Is Tay-Sachs Disease? Tay-Sachs disease is a fatal inherited disease of the central nervous system. The most common form of the disease affects babies. Affected babies appear healthy at birth and seem to develop normally for the first few months of life. After this time, development slows and symptoms begin. Sadly, there is no effective treatment for these babies. Babies with Tay-Sachs lack an enzyme (protein) called hexosaminidase A (hex A) necessary for breaking down certain fatty substances in brain and nerve cells. These substances build up and gradually destroy brain and nerve cells, until the entire central nervous system stops working. Symptoms of classical Tay-Sachs disease first appear at 4 to 6 months of age when an apparently healthy baby gradually stops smiling, crawling or turning over, loses its ability to grasp or reach out and, eventually, becomes blind, paralyzed and unaware of its surroundings. Death occurs by age 5. Who Is at Risk of Tay-Sachs Disease? Tay-Sachs disease occurs most frequently in descendants of Central and Eastern European (Ashkenazi) Jews. About one out of every 30 American Jews carries the Tay-Sachs gene. Some non-Jewish individuals of French-Canadian ancestry (from the East St. Lawrence River Valley of Quebec), and members of the Cajun population in Louisiana, are at similarly increased risk. These groups have about 100 times the rate of occurrence of other ethnic groups. The juvenile form of Tay-Sachs, however, may not be increased in these groups. How Is the Disease Transmitted? Only through heredity. A Tay-Sachs carrier has one normal gene for hex A and one Tay-Sachs gene. The carrier does not have the illness and leads a normal, healthy and full life. However, when two carriers become parents: There is a one-in-four chance that any child they have will inherit a Tay-Sachs gene from each parent and have the disease. There is a one-in-four chance that the child will inherit the normal gene from each parent and be completely free of the disease and the Tay-Sachs gene. There is a two-in-four chance that the child will inherit one of each kind of gene and be a carrier like the parents and free of disease. If only one parent is a carrier, none of their children can have the disease, but each child has a 50-50 chance of inheriting the Tay-Sachs gene and being a carrier. Are There Other Forms of Tay-Sachs Disease Besides the Classical Type That Affects Babies? The classic infantile type of Tay-Sachs is the most common. However, there are other rare deficiencies of the hex A enzyme that sometimes are included under the name of Tay-Sachs disease. These often are referred to as juvenile, chronic and adult-onset forms of hex A deficiency. Affected individuals have low levels of the hex A enzyme that is missing entirely in the classical, infantile form. This may help explain why symptoms begin later in life and, generally, are milder than in the classical, infantile Tay-Sachs disease. Children with juvenile hex A deficiency develop symptoms between the ages of 2 and 5 that resemble those of the classical, infantile form. Although the course of the disease is slower, death generally occurs by age 15. Symptoms of chronic hex A deficiency also may begin by age 5, but are far milder than those that characterize the infantile and juvenile forms. Mental abilities, vision and hearing remain intact; but there may be slurred speech, muscle weakness, muscle cramps, tremors, unsteady gait and, sometimes, mental illness. Individuals with adult-onset hex A deficiency experience many of the same symptoms as individuals with the chronic form, but the symptoms begin later in life. Is There Any Treatment for Tay-Sachs? Tragically, there is no cure, and no treatment that will prevent the disease from running its course. Affected children can only be made as comfortable as possible. Can Tay-Sachs Disease Be Diagnosed Before Birth? Yes. Prenatal tests called amniocentesis and chorionic villus sampling (CVS) can diagnose Tay-Sachs before birth. In amniocentesis, which usually is done between the 15th and 18th week of pregnancy, a needle is inserted into the mother’s abdomen to take a sample of fluid that surrounds the fetus. The fluid contains fetal cells that can be examined for the presence of hex A. In CVS, the doctor retrieves a sample of cells either through a thin tube inserted through the vagina and cervix to the placenta or by inserting a needle through the mother’s abdomen. The placenta contains cells that are genetically identical to those of the fetus, and these cells are examined for the presence of hex A. CVS usually is done between the 10th and 12th week of pregnancy. If prenatal testing shows that hex A is present, the baby will not have Tay-Sachs. If it is missing, he or she will be affected. In unusual cases, DNA-based genetic testing can determine whether the fetus has infantile Tay-Sachs or another hex A deficiency and, possibly, how severely affected the baby will be. Other approaches using in vitro fertilization (with genetic testing of the embryos, so that only healthy ones are implanted in the mother) are under investigation, but the safety and accuracy of these methods are as yet uncertain. How Can People Find out if They Are Carriers? You can take a test that measures the amount of the hex A enzyme in your blood. Tay-Sachs carriers have about half as much of the enzyme as noncarriers, but this is plenty for the carrier’s own needs.    A blood sample also can be used to perform DNA-based genetic testing. These are tests that look for known mutations (changes) in the hex A gene that cause the four forms of Tay-Sachs. This kind of testing may be recommended if the results of the usual carrier screening test discussed above are uncertain. DNA tests also can be used to diagnose late onset forms of hex A deficiency. Where Is Carrier Screening Available? Carrier screening for Tay-Sachs is available from a genetic services center or clinic. Your doctor can tell you where testing is available or you can contact the National Tay-Sachs and Allied Diseases Association for information. The genetic services center performs the carrier screening test that can determine whether one or both partners carry the Tay-Sachs gene. Trained genetic counselors will explain the test results, so that you know whether or not your children will be at risk of the disease. What Research on Tay-Sachs Disease Is Being Conducted by March of Dimes Grantees? March of Dimes sponsored researchers have helped pinpoint the various mutations in the hex A gene that are responsible for the rare forms of hex A deficiency. Information about specific mutations leads to improved diagnosis and carrier screening for all forms of Tay-Sachs. The March of Dimes also supports many grants for research on gene therapy, in which scientists transfer a normal gene into cells to replace an abnormal or missing gene. The goal is to cure or alleviate the symptoms of certain genetic diseases. This revolutionary new form of treatment is being tested in patients with several genetic diseases and, eventually, this approach also may hold promise for children with Tay-Sachs. How Can I Learn More About Tay-Sachs? Families affected by Tay-Sachs disease can contact The National Tay-Sachs and Allied Diseases Association, Inc. The Association is involved in research and educational programs related to the prevention and treatment of Tay-Sachs, provides families with referrals to medical resources, and also coordinates a parent support network. You can contact the Association at: The National Tay-Sachs and Allied Diseases Association, Inc. 2001 Beacon St., Suite 204 Brookline, MA 02135 Telephone: 617-277-4463 (800) 906-8723 E-mail: mpf@bellatlantic.net You also may contact: Late Onset Tay-Sachs Foundation 1303 Paper Mill Road Erdenheim, PA 19038 (800) 672-2022 (214) 836-9426 E-mail: mpf@bellatlantic.net References Gravel, R.A., etal. The GM2 Gangliosidoses, in Scriver, C.R. et al (eds.): The Metabolic and Molecular Bases of Inherited Disease Seventh Edition, New York, McGraw Hill, 1995, pages 2839-2879. National Tay-Sachs and Allied Diseases Association, Inc. Tay-Sachs Disease (Classical Infantile Form), 1999. Rutledge, S.L., Percy, A.K. Gangliosidoses and related storage diseases, in Rimoin, D.L. et al (eds.): Emery and Rimoin’s Principles and Practice of Medical Genetics Third Edition, New York, Churchill Livingstone, 1996, pages 2105-2130.     © 2008 March of Dimes Birth Defects Foundation. All rights reserved. The March of Dimes is a not-for-profit organization recognized as tax-exempt under Internal Revenue Code section 501(c)(3). Our mission is to improve the health of babies by preventing birth defects and infant mortality.