brief description

Tay-Sachs disease is a fatal genetic disorder in children that causes the progressive destruction of the central nervous system. Due to a deficiency of a vital enzyme called hexosaminidase A (Hex-A), harmful quantities of a fatty substance called ganglioside GM2 accumulate in the nerve cells of the brain. As the nerve cells become distended with fatty materials, the cells become damaged and gradually lose their ability to function properly. The affected child fails to develop appropriate mental and motor functions.

Tay-Sachs is categorized as a lysosomal storage disease. Lysosomes are the major digestive units in cells. Enzymes within lysosomes break down or "digest" nutrients, including certain complex carbohydrates and fats.

Affected children show developmental abnormalities and delays during the first three to eight months of life. In the course of the disease, infants may have an exaggerated startle response to sudden noises, decreased eye contact, and exhibit listlessness. A "cherry-red spot" may be seen in the macula at the back of the eye.

The infant gradually regresses, losing previously acquired skills one by one (known as psychomotor regression). Muscle tone is diminished (hypotonia) and muscles become increasingly stiff. By about two years, most children experience recurrent seizures (uncontrolled electrical disturbances in the brain) and diminishing mental function. Affected children also develop seizures which are not always controllable with anti-epileptic drugs after this time. Loss of swallowing function occurs progressively together with increased risk for aspiration and subsequent chest and lung infections. The child eventually becomes blind, paralyzed, and nonresponsive to his or her environment. There is progressive dependence on external support.

Tay-Sachs disease is an inherited metabolic disorder. Both parents must be carriers in order to have an affected child. Carrier screening and genetic counseling have made this disease rare in those at known risk.

Populations known to be at higher risk include people of Askenazic Jewish (Central or Eastern European), French-Canadian, and Cajun descent (1 in 27). Current research also estimates the carrier rate may be higher in Irish Americans, around 1 in 50 people. While there are certain populations at higher risk, anyone can be a carrier of Tay-Sachs.  Today, most patients are seen in families with no prior history of the disease, because the recessive gene can be carried without being expressed through many generations.

Patients and carriers of Tay-Sachs disease can be identified by a simple blood test that measures hexosaminidase A activity.

There are 2 types of tests for Tay-Sachs: enzyme assay or DNA studies.

1) The enzyme assay is a biochemical test that measures the level of Hex-A in a person's blood serum, in plasma or white blood cells. Carriers have less Hex-A in their body fluid and cells than non-carriers. Babies with infantile Tay-Sachs disease have a total absence of Hex-A in their cells.

2) DNA-based carrier testing looks for specific mutations in the gene that codes for Hex-A. Since 1985, when the Hex-A gene was isolated, over 50 different mutations in this gene have been identified. The limitation of DNA-based carrier testing is that not all known mutations in the Hex-A gene are detected by the test, as others have yet to be identified. The tests currently detect about 95% of carriers of Ashkenazi background and about 60% of non-Jewish individuals. Therefore, some people who are carriers will not be identified by DNA analysis alone.

*The information expressed here was taken from several sources including: What Every Family Should Know (NTSAD-1996), Rudolph's Pediatrics-20 ed. (1996), National Institute of Neurological Disorders and Stroke Fact Sheet on Tay-Sachs Disease (2000), and information from the National Organization for Rare Disorders (2000).

Further information is available from these organizations (last updated May, 2001):