The Tay-Sachs chromosome is located on chromosome number 15, and is also known as the hexosaminidase A (or HEXA) gene. In Tay-Sachs disease, this gene is defective, causing an abnormality in the breakdown of lipids, which results in a toxic accumulation of GM2 ganglioside in the brain and spinal cord. Severe mutations of the Tay-Sachs chromosome become apparent in infancy; less severe mutations manifest later in life.
The Tay-Sachs chromosome is chromosome number 15. This is also known as the hexosaminidase A (alpha polypeptide) gene, or HEXA gene for short.
The HEXA gene instructs cells to make one part of an enzyme called beta-hexosaminidase A. Specifically, the HEXA gene makes the portion called alpha subunit of this enzyme. A functioning enzyme is created when one alpha subunit comes together with one beta subunit (made by the HEXB gene).
Beta-hexosaminidase A is found in lysosomes, which are structures in cells that break down toxic substances and act as the cell's recycling center. Within lysosomes, beta-hexosaminidase A forms part of a complex that breaks down a fatty substance called GM2 ganglioside.
Tay-Sachs disease is caused by mutations in the HEXA gene. More than 95 mutations that cause the disease have been identified. These mutations reduce or eliminate the activity of the enzyme beta-hexosaminidase A, preventing the normal breakdown of GM2 ganglioside in the brain and spinal cord. As a result, this substance builds up to toxic levels in nerve cells. Progressive damage caused by the buildup of GM2 ganglioside leads to the destruction of these cells, causing the signs and symptoms of Tay-Sachs disease.
About 70 of the known mutations in the HEXA gene lead to a completely nonfunctional version of beta-hexosaminidase A. These mutations cause the severe form of Tay-Sachs disease, which begins in infancy. Other mutations, which reduce but do not eliminate the activity of beta-hexosaminidase A, are responsible for the less severe forms of Tay-Sachs disease that appear later in life.