Tay-Sachs disease

Disease Overview

Tay-Sachs disease is a rare, inherited neurodegenerative disease. People with Tay-Sachs disease do not have enough of an enzyme called beta-hexosaminidase A.  The less enzyme a person has, the more severe the disease and the earlier that symptoms appear. There are 3 forms of Tay-Sachs disease, distinguished by the general age of onset:[14280][14281]

• Infantile – the most common severe form, with symptoms appearing in the first few months of life. Symptoms include a loss of skills learned (regression), seizures, and loss of muscle and mental functions. Children with this form do not survive past early childhood.
• Juvenile – a form with a range of severity, with symptoms appearing any time during childhood (but usually between ages 2 and 5). Symptoms include behavior problems, gradual loss of skills, frequent respiratory infections, and seizures. People with this form typically do not survive past their teenage years.
• Late onset/adult – the least severe form, with symptoms appearing in late childhood to adulthood. Symptoms may include clumsiness, muscle weakness, psychiatric disorders, and gradual loss of skills, often leading to the need for mobility assistance. Intellect and behavior become impaired in some cases. The lifespan varies from shortened to unaffected.

Tay-Sachs disease is caused by mutations in the HEXA gene and inheritance is autosomal recessive. The HEXA gene gives the body instructions to make part of the beta-hexosaminidase A enzyme, which is needed to break down a substance called GM2 ganglioside. When the enzyme is not functional or not made, GM2 ganglioside builds up in the nerve cells (neurons) of the brain and spinal cord, causing the symptoms of the disease.[61]

The diagnosis of Tay-Sachs disease involves a blood test that detects absent or very low levels of beta-hexosaminidase A enzyme activity. Molecular genetic testing of the HEXA gene may be used to identify the specific mutations present, or to rule out the disease if a false-positive blood test result is suspected.[14284]

Currently there is no cure for Tay-Sachs disease, and there are no therapies that slow the progression of the disease. Treatment aims to relieve symptoms and increase quality of life. For example, children with seizures may be treated with anti-seizure medicines. Adequate nutrition and hydration are recommended, to prevent complications.[14284][14285]

Note: You may also find Tay-Sachs disease referred to as a lysosomal storage disease or a GM2-gangliosidosis because the disease involves a lysosomal enzyme and the buildup of GM2 ganglioside.

Synonyms

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