Tay-Sachs disease is a hereditary human genetic disorder, a form of sphingolipidosis, caused by the absence or deficiency of beta-hexosaminidase, a lysosomal enzyme. Because of this missing or deficient enzyme, body cells store lipids abnormally and eventually suffer damage. Nerve cells in the brain and spinal cord accumulate excessive levels of ganglioside sphingolipids, leading to progressive neurological problems. There is no cure or specific treatment for Tay-Sachs disease. See also: Enzyme; Genetics; Glycoprotein; Lysosome; Metabolic disorders; Sphingolipid
Of the three forms of the disease in humans, classic infantile Tay-Sachs disease (formerly termed infantile amaurotic familial idiocy) is most prevalent. Its symptoms begin to appear about 7 months after birth, and it is typically fatal by 4 years of age. Clinical manifestations include hypotonia (reduced muscle tone) progressing to spasticity, convulsions, hearing loss, and vision loss accompanied by the characteristic appearance of a cherry-red spot at the macula lutea on the retina of the eye. Juvenile Tay-Sachs disease, a rarer form that appears between ages 2 and 10, is usually fatal by 5 to 15 years of age. Adult- or late-onset Tay-Sachs disease occurs later in life, most often in individuals who are 30 or 40 years old. This form is highly debilitating, but it is not always fatal, and many affected individuals do not have the reduced life spans as seen in the other forms of Tay-Sachs disease.
Tay-Sachs is named for two of the original investigators of this disease: the British ophthalmologist Warren Tay (1843–1927) and the New York neurologist Bernard Sachs (1858–1944). They provided early signposts that enabled later scientists to pinpoint the exact enzyme deficiency in the late 1960s. Further research in the 1980s finally identified the mutated gene responsible for the defective enzyme in Tay-Sachs disease and determined that its position is on chromosome 15 (specifically 15q23-q24). See also: Chromosome; Chromosome aberration; Gene; Mutation
Tay-Sachs disease is an autosomal (nonsex chromosome) recessive genetic disorder. Consequently, females and males are affected at equal rates. In order to pass the disease to a child, both parents must be carriers of the defective gene; in these cases, there is a 25% chance that a pregnancy will result in a child affected by Tay-Sachs disease. Within the general population, the carrier rate for Tay-Sachs disease is 1 out of 250 people. However, Ashkenazi Jews from Eastern and Central Europe, French-Canadians of Quebec origin, Cajuns from Louisiana, and Amish in Pennsylvania have increased risks compared to the general population: Among them, the carrier rates can run as high as 1 out of 27. A blood test can determine if a person is a carrier for Tay-Sachs disease. Prenatal diagnosis, including amniocentesis, can identify whether a fetus has Tay-Sachs disease. See also: Human genetics; Pregnancy; Prenatal diagnosis