Alternative Names
B variant GM2 gangliosidosis; GM2 gangliosidosis, type 1; HexA deficiency; Hexosaminidase A deficiency; Hexosaminidase alpha-subunit deficiency (variant B); Sphingolipidosis, Tay-Sachs; TSD; Tay-Sachs
Symptoms & Characteristics
Tay-Sachs disease (commonly called Tay-Sachs) is a genetic condition that causes progressive destruction of nerve cells in the brain and spinal cord (the central nervous system). There is more than one type of Tay-Sachs disease, but the most common type is the infantile form.
The infantile form is so named as symptoms appear 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. They also develop an exaggerated startle reaction to loud noises. As the disease progresses, children with Tay-Sachs disease experience 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 infantile form of Tay-Sachs disease usually survive 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 (called 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.
Treatment
There is currently no treatment for Tay-Sachs disease. Anticonvulsant medicine may initially control seizures. Other supportive treatment includes proper nutrition and hydration and techniques to keep the airway open. Children may eventually need a feeding tube. Children with this severe infantile form of Tay-Sachs disease usually survive only into early childhood.
How Common Is It?
Tay-Sachs disease is not common in the general population.
Tay-Sachs disease is more common in people of Ashkenazi (eastern and central European) Jewish ancestry, certain French-Canadian communities of Quebec, the Old Order Amish community in Pennsylvania, the Cajun population of Louisiana, as well as in people of Irish or Moroccan Jewish ancestry.
Genetics & Inheritance
Tay-Sachs disease is caused by a gene called HEXA on the chromosome 15 at the location q23-q24. The HEXA gene provides instructions for making part of an enzyme called beta-hexosaminidase A, which plays a critical role in the central nervous system.
More than 100 mutations have been identified in the HEXA gene. Mutations in the HEXA gene disrupt the activity of the beta-hexosaminidase A enzyme.
- Of note, not all affected individuals have mutations that can be identified by current DNA testing methods.
- Three specific mutations cause most cases of the disease in people of Ashkenazi Jewish ancestry.
- Two specific mutations cause a "pseudodeficiency" of the enzyme. This means that although these mutations cause reduced enzyme activity in the laboratory, they do not actually cause the disease in a person.
We all have two copies of the HEXA gene - one from each parent. In Tay-Sachs disease, it is necessary to have two mutations, one in each gene copy, to be affected. This is called autosomal recessive inheritance.
- Both parents of an affected person are always both obligate carriers (have only one mutation). Two carriers have a 25% chance with each pregnancy to have an affected child, but do not have symptoms themselves.
- Without a family history, the chance to be a carrier is determined by a person's ethnic background. For example, 1 in 30 people of Ashkenazi Jewish ancestry or French-Canadian ancestry are carriers of Tay-Sachs disease.
Testing
Clinical genetic testing for Tay-Sachs disease can be broken down into two categories: diagnostic testing and carrier testing.
- Diagnostic testing may be used to confirm or rule out a diagnosis in a person suspected to have the disorder. Alternatively, special biochemical blood plasma or white blood cell testing can also be used to confirm or rule out a diagnosis. Of note, biochemical blood plasma testing can be complicated by pseudodeficiency mutations (in both males and females) as well as by being pregnant or on birth control (in females only). Either biochemical white cell testing or DNA diagnostic testing may be more informative depending on the situation.
- Carrier testing is typically offered after a clinical diagnosis and/or mutations have already been identified in an affected family member(s). Carrier testing is also available for people of high risk ethnic groups. Biochemical testing can also be used for carrier testing purposes with the same limitations.
Carrier testing for the Ashkenazi-specific mutations that cause Tay-Sachs disease is available online (over the internet). This testing is available individually or as part of an Ashkenazi Jewish panel. Go to the Tests tab to link to the best providers, compare providers and read provider reviews.
Diagnostic testing and carrier testing for people who are not of Ashkenazi Jewish ancestry is available through an in person genetic consultation for people who are considered at risk. Use our find a genetic professional directory to locate a trained genetic professional in your area.
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