TSD is a genetic metabolic disorder caused by a lack of the enzyme hexosaminidase A (hex-A). This deficiency results in a failure to process an essential lipid (called GM2 ganglioside) that accumulates in the brain and other tissues.
The classic form of TSD begins in infancy. Babies with TSD usually develop normally for the first few months, but head control is lost by six to eight months of age. This prevents the babies from being able to roll over or sit up. Symptoms include spasticity and rigidity, and excessive drooling and convulsions. Blindness and head enlargement occur by the second year. The disease worsens as the central nervous system progressively deteriorates. After age two, constant nursing care is needed. Children with TSD rarely live beyond age five.
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. Knowledge of the biochemical basis of TSD now permits screening for carrier status and prenatal diagnosis.