Tay-Sachs Disease (TSD), rare genetic disorder of the central nervous system that leads to progressive brain deterioration and death. Babies born with TSD appear to develop normally for about six months but then develop signs of rapid deterioration of physical and mental functions that lead to blindness, seizures, mental retardation, inability to swallow, respiratory problems, and paralysis. There is no cure for TSD—even with the best of care, children with the disease die in early childhood, usually by the age of five. An estimated 20 cases of TSD are diagnosed in the United States each year.
TSD is caused by a defective gene that is unable to produce the enzyme hexosaminidase A (hex A). This enzyme is necessary to break down GM2 ganglioside, a fatty substance in the nerve cells of the brain. Children with TSD have no hex A; as a result, GM2 ganglioside builds up in their brain cells, causing the cells to degenerate and die. Although this process begins in the fetus early in the mother’s pregnancy, the TSD symptoms are not apparent until GM2 ganglioside has built up to toxic levels in the brain.
Other hex A deficiencies cause two rare diseases that are often included under the name of Tay-Sachs disease. Juvenile TSD occurs later in childhood, usually between the ages of two and five, and progression of the disease is slower than that of classical TSD. Like classical TSD, juvenile TSD is untreatable and invariably fatal.
TSD is an autosomal recessive genetic disorder—that is, a child must inherit two copies of the defective gene, one from each parent. Many people carry a single Tay-Sachs gene; in the general population, approximately 1 in 300 individuals carries the gene. These individuals produce less hex A than noncarriers, but they do not experience any health problems as a result. The disease can only develop when both parents are carriers, in which case they have a one in four chance with every pregnancy of having a child with TSD.
Certain ethnic populations include more people who carry the defective TSD gene. High-risk groups include Ashkenazic Jews of Eastern European ancestry; one in 30 Ashkenazic Jews carries the Tay-Sachs gene. Other groups at high risk include French Canadians and certain Cajun communities in rural Louisiana.
A simple blood test can determine if an individual carries the Tay-Sachs gene. High-risk individuals should be tested for the gene before marriage and pregnancy. If both partners are identified as carriers, genetic counselors can help the couple understand their reproductive risk and options.