Tay–Sachs Disease

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Tay-Sachs disease is a genetically inherited, neurodegenerative disorder. Individuals affected with the disease experience abnormal brain development that gets progressively worse. The outcome is a life expectancy of no more than five years of age due to complications related to the disorder.

The disease is named after British ophthalmologist Warren Tay (1843–1927) and New York neurologist Bernard Sachs (1858–1944), who both described symptoms of the disease. Sachs also noted the genetic component of the disorder, recognizing that most affected babies were of eastern European Jewish descent.

Tay-Sachs disease is inherited from one’s parents, who do not display any symptoms. In genetic terms, the disease is an autosomal recessive disorder. Put another way, the parents have a defective gene but because the gene is not expressed, they do not have symptoms. However, if two parents who each have a defective gene produce a child, the child can inherit both copies of the defective gene, one from each parent. The child will express the disease.

The defective gene produces a protein, specifically an enzyme called hexosaminidase A, which is important for speeding up a specific biochemical reaction. The enzyme defect leads to the accumulation of a compound called GM2 ganglioside, a fatty substance found enriched in nerve cells of the brain. The accumulation of this compound in the brain leads to the deterioration of both mental and physical development. Children become blind, deaf, and unable to swallow food, and eventually experience paralysis due to muscular degeneration. The reason Tay-Sachs disease symptoms become progressively worse with age is because the compound keeps accumulating over time. This fatty substance can accumulate even during pregnancy, where the first destructive effects take place, although the clinical significance does not appear until the first few months after birth.

Symptoms vary in severity and the time in which they are evident. Failure to develop, loss of vision, and a characteristic abnormal startle reaction to sounds are often helpful considerations in making a diagnosis.

Although Tay-Sachs disease primarily affects infants, juvenile and adult forms of Tay-Sachs disease also exist. A rarer form occurs in affected individuals who are in their late twenties or early thirties. This form is characterized by progressive neurological degeneration with the first recognized abnormality being an unsteady gait.

Certain populations are known to be at a higher risk for carrying a defective Hex-A gene. However, anyone in a population can be a carrier of Tay-Sachs disease. The defective Tay-Sachs allele is prevalent in Jews of eastern European descent. About 1 in 27 people of this descent are thought to be carriers, and about 1 in 3,600 Jewish infants are born with this disease, accounting for approximately 90% of all Tay-Sachs cases worldwide. Among non-Jews, about 1 in 300 people are carriers of the defective allele. Carriers do not have symptoms of Tay-Sachs, although their levels of the hexosaminidase A enzyme may be reduced as much as 50%. This reduction, however, is not sufficient to produce symptoms.

Patients and carriers can be identified by a simple blood test that measures the activity of the affected enzyme. Identification can also be made by the genetic detection of the defective gene in a sample of blood withdrawn from both parents.

The genetic test can detect three genetic changes (mutations) responsible for Tay-Sachs disease. Two of these mutations cause the infantile form of the disease. By testing for the existence of these mutations in a person’s blood, carriers are more accurately identified. As of 2006, testing detects about 95% of carriers in the Ashkenazi Jewish populations and about 60% of non-Jewish individuals. This test can assist parents in making reproductive decisions. DNA testing is currently the accepted approach to test individuals of confirmed Ashkenazi Jewish descent, whereas newborn screening programs can use dried blood spots on filter paper to measure enzyme activity. For prenatal diagnosis, enzyme levels can be measured in amniotic fluid by a procedure called amniocentesis. As in all genetic testing services, the proper genetic counseling and follow-up procedures should always accompany any genetic test.

As of 2006, there is no cure for Tay-Sachs disease. The use of enzyme replacement therapy, where properly functioning enzyme is introduced, has been investigated. Even if successful, this therapy would require a lifelong infusion of the enzyme. Ultimately, the goal would be to use gene therapy to cure Tay-Sachs disease. In gene therapy, cells that have been infected with viruses carrying normal genes are injected into the body. The healthy genes would then produce enough hexosaminidase A to break down the accumulating gangliosides.

Resources

BOOKS

Tay-Sachs Disease: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References. San Diego: Icon Health Publications, 2004.

Wailoo, Keith, and Stephen Pemberton. The Troubled Dream of Genetic Medicine: Ethnicity and Innovation in Tay-Sachs, Cystic Fibrosis, and Sickle Cell Disease. Baltimore: Johns Hopkins University Press, 2006.

Walker, Julie. Tay-sachs Disease. New York: Rosen Publishing Group, 2006.

Bryan Cobb, Ph.D.