Tay-Sachs Disease

Genetic Disorder

More specifically, TSD is an autosomal recessive (not sex-linked and both parents must be carriers to have a child with TSD) disease that occurs when harmful quantities of the fatty acid derivative ganglioside accumulate in nerve cells in the brain. Ganglioside GM2 in Tay-Sachs disease is especially common in the nervous tissue of the brain. Mutations on chromosome 15 and specific to the hexosaminidase A (alpha polypeptide) or HEXA gene are what cause TSD.

Many of these mutations have been discovered and more than 90 mutations have been identified in the HEXA gene. New mutations are still being reported and research is still under way. These mutations include base pair insertions and deletions, splice site mutations, point mutations, and other more complex patterns. Each of these mutations alter the protein product and inhibit the function of the enzyme in some manner causing TSD.

Some populations have higher mutation frequencies than others. For example, French Canadians of southeastern Quebec and Cajuns from southern Louisiana have mutation frequencies similar to those mentioned for Ashkenazi Jews of eastern Europe. TSD can occur from inheritance of two unrelated mutations involving the HEXA gene with one being from each parent.

Types

The juvenile-onset form presents with loss of coordination and dementia. Death ensues by age 10 to 15 years. The adult-onset form is characterized by clumsiness in childhood with progressive motor weakness in adolescence and multiple and neurological disorders with balance, speech, and overall movement. Intelligence declines slowly, and psychosis can occur.

Diagnosis

A simple blood test looking for hexosaminidase A activity can diagnose TSD. Even though this disease is autosomal recessive and both parents have to carry the gene, it is only a 25 percent chance that the child will be born with TSD. Furthermore, prenatal monitoring in the fetus by chorionic villus sampling or amniocentesis is an option. Screening for Tay-Sachs disease carriers is recommended in the Ashkenazi Jewish population.

...