Tay-Sachs disease

Tay-Sachs disease A genetic metabolic disorder caused by deficiency of the enzyme hexosaminidase A (hex-A) that results in failure to process GM2 ganglioside, a lipid (fat) that then 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. 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 forms of TSD are inherited in an autosomal recessive manner and are due to mutation of the gene for the alpha subunit of hexA that is on chromosome 15. The frequency of TSD is relatively high in Ashkenazi Jews (particularly those whose ancestors came from Lithuania and Poland). Knowledge of the biochemical basis of TSD now permits screening for carrier status and prenatal diagnosis. Also known as amaurotic familial idiocy, type 1 GM2-gangliosidosis, B variant GM2gangliosidosis, hexosaminidase A deficiency, and hex-A deficiency. See also Sandhoff disease.