Tay-Sachs disease

Definition

Tay-Sachs disease is a genetic disorder caused by a missing enzyme that results in the accumulation of a fatty substance in the nervous system. This results in disability and death.

Description

Gangliosides are a fatty substance necessary for the proper development of the brain and nerve cells (nervous system). Under normal conditions, gangliosides are continuously broken down, so that an appropriate balance is maintained. In Tay-Sachs disease, the enzyme necessary for removing excess gangliosides is missing. This allows gangliosides to accumulate throughout the brain, and is responsible for the disability associated with the disease.

Tay-Sachs disease is particularly common among Jewish people of Eastern European and Russian (Ashkenazi) origin. About one out of every 3,600 babies born to Ashkenazi Jewish couples will have the disease. Tay-Sachs is also more common among certain French-Canadian and Cajun French families.

Causes and symptoms

Tay-Sachs is caused by a defective gene. Genes are located on chromosomes, and serve to direct specific development/processes within the body. The genetic defect in Tay-Sachs disease results in the lack of an enzyme, called hexosaminidase A. Without this enzyme, gangliosides cannot be degraded. They build up within the brain, interfering with nerve functioning. Because it is a recessive disorder, only people who receive two defective genes (one from the mother and one from the father) will actually have the disease. People who have only one defective gene and one normal gene are called carriers. They carry the defective gene and thus the possibility of passing the gene and/or the disease onto their offspring.

When a carrier and a non-carrier have children, none of their children will actually have Tay-Sachs. It is likely that 50% of their children will be carriers themselves. When two carriers have children, their children have a 25% chance of having normal genes, a 50% chance of being carriers of the defective genne, and a 25% chance of having two defective genes. The two defective genes cause the disease itself.

Classic Tay-Sachs disease strikes infants around the age of six months. Up until this age, the baby will appear to be developing normally. When Tay-Sachs begins to show itself, the baby will stop interacting with other people, and develop a staring gaze. Normal levels of noise will

startle the baby to an abnormal degree. By about one year of age, the baby will have very weak, floppy muscles, and may be completely blind. The head will be quite large. Patients also present with loss of peripheral (side) vision, inability to breath and swallow, and paralysis as the disorder progresses. Seizures become a problem between ages one and two, and the baby usually dies by about age four.

A few variations from this classical progression of Tay-Sachs disease are possible:

Juvenile hexosaminidase A deficiency. Symptoms appear between ages two and five; the disease progresses more slowly, with death by about 15 years.
Chronic hexosaminidase A deficiency. Symptoms may begin around age five, or may not occur until age 20-30. The disease is milder. Speech becomes slurred. The individual may have difficulty walking due to weakness, muscle cramps, and decreased coordination of movements. Some individuals develop mental illness. Many have changes in intellect, hearing, or vision.

Diagnosis

Examination of the eyes of a child with Tay-Sachs disease will reveal a very characteristic cherry-red spot at the back of the eye (in an area called the retina). Tests to determine the presence and quantity of hexosaminidase A can be performed on the blood, specially treated skin cells, or white blood cells. A carrier will have about half of the normal level of hexosaminidase A present, while a patient with the disease will have none.

Treatment

There is no treatment for Tay-Sachs disease.

Prognosis

Sadly, the prognosis for a child with classic Tay-Sachs disease is certain death. Because the chronic form of Tay-Sachs has been discovered recently, prognosis for this type of the disease is not completely known.

Prevention

Prevention involves identifying carriers of the disease and providing them with appropriate information concerning the chance of their offspring having Tay-Sachs disease. When the levels of hexosaminidase A are half the normal level a person is a carrier of the defective gene. Blood tests of carriers reveals reduction of Hexosaminidase A.

When a woman is already pregnant, tests can be performed on either the cells of the baby (amniocentesis) or the placenta (chorionic villus sampling) to determine whether the baby will have Tay-Sachs disease.

Resources

BOOKS

Behrman, Richard, ed. Nelson Textbook of Pediatrics. Philadelphia: W. B. Saunders, 1996.

PERIODICALS

Motulsky, Arno G. "Screening for Genetic Disease." New England Journal of Medicine, 336, no. 18 (May 1, 1997): 1314+.

Rosebush, Patricia I. "Late-Onset Tay-Sachs Disease Presenting as Catatonic Schizophrenia: Diagnostic and Treatment Issues." Journal of the American Medical Association 274, no. 22 (December 13, 1995): 1744.

ORGANIZATIONS

Late Onset Tay-Sachs Foundation. 1303 Paper Mill Road, Erdenheim, PA 19038. (800) 672-2022.

March of Dimes Birth Defects Foundation. National Office. 1275 Mamaroneck Avenue, White Plains, NY 10605. (888) 663-4637. resourcecenter@modimes.org. <http://www.modimes.org>.

National Tay-Sachs and Allied Diseases Association, Inc. 2001 Beacon Street, Suite 204, Brighton, MA 02146. (800) 906-8723. Fax: 617-277-0134. NTSAD-Boston@worldnet.att.net. <http://www.ntsad.org>.