Tay-Sachs Disease

Tay-Sachs disease (TSD) is an inherited disorder caused by deficiency of Hexosaminidase A enzyme. This enzyme is necessary to break down fatty substances in the cells of the nervous system. Accumulation of these fatty substances causes the brain and spinal cord nerve cells to malfunction. Children with TSD have normal development until about 6 months of age at which time they present with loss of motor skills, decreased attentiveness, and increased startle response. As the disease progresses, children with TSD develop deafness, blindness, paralysis, seizures, and death usually occurs by age 3-4 years. There is no treatment available for TSD. In addition to TSD other forms of Hexosaminidase A deficiencies exist. They include the juvenile (subacute), chronic, and adult onset disease. These tend to have later onset, slower course, and variable neurologic outcome. TSD is caused by pathogenic variants in the HEXA gene.

TSD is inherited in an autosomal recessive manner. This type of inheritance requires the presence of two copies of a pathogenic variant in the gene for a person to have the genetic disease. Both parents must be carriers of a pathogenic variant in the gene in order to be at risk to have an affected child. The child must inherit a pathogenic variant from each carrier parent in order to be affected. There is a 1 in 4 chance that a baby will inherit two mutated copies of the gene and be affected when both parents are carriers.

There are no signs or symptoms associated with being a carrier for TSD. However, the risk to have a child affected with TSD is increased. Testing of reproductive partners is recommended for carriers of TSD.

TSD is more common in the Ashkenazi Jewish, French Canadians of the eastern St. Lawrence River Valley area of Quebec, Louisiana Cajuns, and the Old Order Amish in Pennsilvania. TSD occurs in about 1 in 3600 newborns in these populations. TSD is less common in other ethnic groups, occuring in about 1 in 250,000 to 1 in 360,000 newborns.

Genetics Home Reference: Tay-Sachs disease (http://ghr.nlm.nih.gov/)
Genetic Alliance: Tay Sachs disease (http://www.diseaseinfosearch.org/)

OMIM [TSD:272800] (http://www.ncbi.nlm.nih.gov/omim)
Gene Reviews: Hexaminidase A Deficiency (http://www.ncbi.nlm.nih.gov/books/NBK1116/)

• Full gene sequencing
• Copy number analysis: promoter