Chicago Center for Jewish Genetics Disorders - Ashkenazi Disorders: Tay-Sachs Disease

Ashkenazi Disorders: Mendelian

Gene: Tay-Sachs disease is caused by mutations in the HEXA gene, which is located at 15q23-q24. This gene encodes beta-hexosaminidase A, the lysosomal enzyme that catalyzes the hydrolysis of ganglioside GM2 to GM3 and N-acetylgalactosamine.

Mutations and carrier testing: Both DNA analysis and enzyme assay are recommended for the highest carrier detection rate. Three mutations account for the majority of mutant alleles seen in the Ashkenazi Jewish population: 1277insTATC, 1421+1G->C, and G269S. When testing of these three mutations is combined with enzyme analysis, carrier detection rate is ~98%.

Traits: Tay-Sachs disease (TSD) is caused by progressive neurodegeneration due to accumulation of GM2 ganglioside in neuronal lysosomes. In the classical form of TSD, onset occurs at 3 to 6 months of age with progressive weakness, loss of motor skills, increased startle response and myoclonic jerks. A macular cherry red spot is seen by direct ophthalmoscopy. Within a few months the child begins to lose visual attentiveness, has decreased voluntary movements and responsiveness, and develops seizures. The disease progresses rapidly until the child becomes completely unresponsive. Death usually occurs by 2 to 4 years of age from bronchopneumonia.

Treatment: There is no effective treatment for Tay-Sachs disease. Supportive care is aimed at providing the affected child with comfort.

Other: The American College of Obstetrics and Gynecology considers Tay-Sachs carrier screening to be standard of care for Ashkenazi Jewish couples. It should be offered to all couples in which one or both partners is of Ashkenazi Jewish descent who are pregnant or planning a pregnancy.

Tay-Sachs Disease from Geneclinics.org
http://www.genetests.org/profiles/tay-sachs

Reviewed by Joel Charrow, MD, Head, Division of Genetics, Birth Defects and Metabolism, Children’s Memorial Hospital, 8/07.

<< Back

This page last updated on September 7, 2007.