Tay-Sachs Disease

September 28, 2011

Tay-Sachs disease (TSD) is a fatal genetic disorder named after Warren Tay (1843-1927) and Bernard Sachs (1858-1944). Tay was a British ophthalmologist who, in 1881, described the occurrence of cherry-red spots (“Tay’s spots”) on the retinas of three siblings. Sachs was an American neurologist who, in 1887, described cellular changes occurring in the disorder. Sachs also recognized the disorder’s familial nature and later, after seeing more cases, noted that most cases occurred in infants of eastern European Jewish descent.

CLINICAL PRESENTATION

Infants with Tay-Sachs disease typically seem to be normal until age 3-6 months. Often, infants will have a porcelainlike complexion and long eyelashes. The onset of the illness is usually insidious, but the disease progresses rapidly. Normal development slows, and the baby may show an increased startle response. infants will start to lose already-developed skills, such as sitting up unsupported and crawling. By age 2 years, most children exhibit slowed mental functioning and recurrent seizures. Children eventually become blind, deaf, mentally retarded, and paralyzed. Swallowing difficulties may lead to the placement of feeding tubes. Twenty-four-hour care, either in a care facility or in the home, is typically required due to the multitude of medical complications. They usually have chronic respiratory difficulties from the age of 2 years on, and death is often due to pneumonia. Children with Tay-Sachs disease die early, generally by age 5.

CAUSE OF TAY-SACHS DISEASE

Children with Tay-Sachs disease lack an important enzyme, hexosaminidase A (hex-A), which breaks down lipids in the brain and central nervous system. The absence of hex-A causes a lipid called GM2 ganglioside to accumulate in brain cells, damaging them irreversibly. Other disorders of hex-A production may be included under the name Tay-Sachs disease, such as juvenile-, chronic-, and adult-onset hex-A deficiency. These other disorders tend to have slower courses, but life span is shortened.

Tay-Sachs disease has been linked to alterations in chromosome 15—more than 50 mutations have been identified in the gene. The disorder appears to have originated in a population of eastern European (Ashkenazi) Jewish families in the early 1800s. The disease is by no means an exclusively Jewish genetic disease, although approximately 85% of patients with Tay-Sachs disease are Jewish. While 1 in 30 people of central or eastern Jewish descent carry the gene for Tay-Sachs disease, approximately 1 in 300 people in the general population carry the gene as well. Clusters of cases have also been described in populations of French Canadians and Louisiana Cajuns. it is an autosomal recessive genetic condition, meaning that both parents must be carriers of the recessive Tay-Sachs disease gene (each has the Tay-Sachs disease in their genetic makeup), and pass the recessive gene on to their child for the child to develop the disease. For two carriers, the chance of having an unaffected (healthy), noncarrier offspring (no Tay-Sachs disease gene) is 25%. For these same two carriers, the chance of having a nondiseased but carrier offspring (has Tay-Sachs disease gene) is 50%. For these same two carriers, the chance of having a child with Tay-Sachs disease is 25%. If only one parent is a carrier, no children will inherit two copies of the recessive gene, so none will have Tay-Sachs disease. However, each child of such a union has a 50% chance of inheriting the recessive gene, and thus being a carrier himself or herself.

DETECTION AND TREATMENT

There is no known cure for Tay-Sachs disease; medical therapy is supportive. Attempts to treat the disorder using a specific type of enzyme replacement (hex-A enzyme replacement) have been unsuccessful because this protein cannot cross the blood-brain barrier and get to the affected brain cells. Tay-Sachs disease can, however, be detected both before birth (prenatally), by procedures that sample the fluid or tissue around the fetus (amnio-centesis or chorionic villus sampling), and after birth, via a simple blood test. Since 1971, screening programs have been in effect and have greatly reduced the incidence of Tay-Sachs disease in the United States through genetic counseling, use of alternative reproductive options, and therapeutic abortion. Blood testing reveals how much hex-A is present, and by inference how many working genes the person has. An infant with Tay-Sachs disease has no circulating hex-A. Carriers, individuals who have one normal gene and one recessive gene, have approximately half the normal amount of hex-A. When carriers are identified, relatives should be tested to detect other potential carriers. It is very important for carrier couples to participate in genetic counseling to assess risks and potential alternative reproductive options such as adoption or artificial insemination with noncarrier sperm.

See Also: Adoption, Genetic counseling, Neonatal care ethics, Reproductive technologies

Suggested Reading

  • Ford, L., & Nissenbaum, M. (1998). Tay—Sachs Disease. In L. Phelps (Ed.), Health-related disorders in children and adolescents: A guidebook for understanding and educating (pp. 636—640). Washington, DC: American Psychological Association.
  • Bellenir, K. (Ed.). (1996). Tay—Sachs disease. Genetic disorders sourcebook. Detroit, MI: Omnigraphics.

 

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