HEXA

The HEXA gene provides instructions for making one part (subunit) of an enzyme called beta-hexosaminidase A. Specifically, the protein produced from the HEXA gene forms the alpha subunit of this enzyme. One alpha subunit joins with one beta subunit (produced from the HEXB gene) to form a functioning enzyme.

Beta-hexosaminidase A plays a critical role in the brain and spinal cord (central nervous system). This enzyme is found in lysosomes, which are structures in cells that break down toxic substances and act as recycling centers. Within lysosomes, beta-hexosaminidase A forms part of a complex that breaks down a fatty substance called GM2 ganglioside.

Tay-Sachs disease - caused by mutations in the HEXA gene

More than 120 mutations that cause Tay-Sachs disease have been identified in the HEXA gene. These mutations reduce or eliminate the activity of the enzyme beta-hexosaminidase A, which prevents the enzyme from breaking down GM2 ganglioside. As a result, this substance builds up to toxic levels, particularly in nerve cells in the brain and spinal cord. Progressive damage caused by the buildup of GM2 ganglioside leads to the destruction of these cells, which causes the signs and symptoms of Tay-Sachs disease.

Most of the known HEXA mutations result in a completely nonfunctional version of beta-hexosaminidase A. These mutations cause the severe form of Tay-Sachs disease, which appears in infancy. Other mutations reduce but do not eliminate the activity of beta-hexosaminidase A; these genetic changes are responsible for the less severe forms of Tay-Sachs disease, which appear later in life.