Definition of Tay-Sachs disease

Tay-Sachs disease: A genetic metabolic disorder caused by deficiency of the enzyme hexosaminidase A (hex-A) that results in a failure to process a lipid called GM2 ganglioside that accumulates in the brain and other tissues. Abbreviated TSD.

The classic form of TSD begins in infancy. The child usually develops normally for the first few months, but head control is lost by 6 to 8 months of age; the infant cannot roll over or sit up, spasticity and rigidity develop, and excessive drooling and convulsions become evident. Blindness and head enlargement occur by the second year. The disease worsens as the central nervous system progressively deteriorates. After age 2, constant nursing care is needed. Death generally occurs by age 5, due usually to cachexia (wasting away) or aspiration pneumonia. There are several forms of TSD. With juvenile TSD and adult TSD, the person has somewhat more hex-A and hence a later onset of clinical disease than with infantile TSD.

All known forms of TSD are inherited in autosomal recessive manner and are due to mutation of the gene for the alpha subunit of hex-A that is on chromosome 15q23-15q24. The frequency of TSD is relatively high in Ashkenazi Jews, particularly those whose ancestors came from Lithuania and Poland. This is believed due to founder effect, mutation in one of the founders of this group of people. Knowledge of the biochemical basis of TSD now permits screening for carrier status and prenatal diagnosis.

The disease is named for the English physician Waren Tay and New York neurologist Bernard (Barney) Sachs who made key early contributions to the rocognition of this disease. In 1881 Tay described an infant he had seen with progressive neurological impairment and the "cherry-red spots" in the retina characteristic of TSD. Sachs saw a child in 1887 and the child's sister in 1898 with the cherry-red spots and "arrested cerebral development" and in 1910 he demonstrated the presence of accumulated lipid in the brain and retina.

TSD was once called amaurotic familial idiocy (a term to avoid) and today it is also known as type 1 GM2-gangliosidosis, B variant GM2-gangliosidosis, hexosaminidase A deficiency, and hex-A deficiency. See also: Sandhoff disease.