Tay-Sachs Disease

What is Tay-Sachs disease?

Tay-Sachs disease is a rare inherited disorder that causes progressive destruction of nerve cells in the brain and spinal cord.

The most common form of Tay-Sachs disease begins in infancy. Infants with this disorder typically appear normal until the age of 3 to 6 months, when development slows and muscles used for movement weaken. Affected infants lose motor skills such as turning over, sitting, and crawling. As the disease progresses, infants develop seizures, vision and hearing loss, mental retardation, and paralysis. An eye abnormality called a cherry-red spot, which can be identified with an eye examination, is characteristic of this disorder. Children with this severe form of Tay-Sachs disease usually live only into early childhood.

Other forms of Tay-Sachs disease are much rarer. Signs and symptoms can begin in childhood, adolescence, or adulthood and are usually milder than those seen with the infantile form of Tay-Sachs disease. As in the infantile form, mental abilities and coordination are affected. Characteristic features include muscle weakness, loss of muscle coordination (ataxia) and other problems with movement, speech problems, and mental illness. These signs and symptoms vary widely among people with late-onset forms of Tay-Sachs disease.

How common is Tay-Sachs disease?

Tay-Sachs disease is very rare in the general population. The genetic mutations that cause this disease are more common in people of Ashkenazi (eastern and central European) Jewish heritage than in those with other backgrounds. In recent years, however, screening for mutations and genetic counselling (including prenatal diagnosis) has made the condition much less frequent in this population.

The genetic mutations that cause Tay-Sachs disease are also more common in certain French-Canadian communities of Quebec, some Amish groups, and the Cajun community of Louisiana.

What genes are related to Tay-Sachs disease?

Mutations in the HEXA gene cause Tay-Sachs disease.

The HEXA gene makes part of an enzyme called beta-hexosaminidase A, which plays a critical role in the nervous system. This enzyme helps break down a fatty substance called GM2 ganglioside in nerve cells. Mutations in the HEXA gene disrupt the activity of beta-hexosaminidase A, preventing the breakdown of GM2 ganglioside. As a result, this compound can accumulate to toxic levels in the brain and spinal cord. Progressive damage caused by the buildup of GM2 ganglioside leads to the destruction of nerve cells, which causes the signs and symptoms of Tay-Sachs disease.

How do people inherit Tay-Sachs disease?

This condition is inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder.

What other names do people use for Tay-Sachs disease?

• B variant GM2 gangliosidosis
• GM2 gangliosidosis, type 1
• HexA deficiency
• Hexosaminidase A deficiency
• Hexosaminidase alpha-subunit deficiency (variant B)
• Sphingolipidosis, Tay-Sachs
• TSD