Tay-Sachs beta-hexosaminidase A active site (4). Inside

Tay-Sachs is an inherited neurodegenerative disorder that affects the central nervous system (1). When the disease will occur in a person depends on how much activity the beta-hexosaminidase A enzyme has in their body (2). The treatment used is supportive and directed to provide comfort since no cure exists (5).
The beta-hexosaminidase A enzyme is made of an alpha and beta subunit (5). An alpha subunit is coded for by the HEXA gene during normal functions (5). The beta-hexosaminidase A enzyme and the GM2 activator protein interact in the lysosome to degrade the GM2 ganglioside. Lysosomes are an important organelle inside the cell that is involved in the breakdown and removal of substances. The GM2 activator protein transports the GM2 ganglioside to the beta-hexosaminidase A active site (4). Inside the active site, the beta-hexosaminidase A hydrolyzes the GM2 ganglioside by cleaving the N-Acetylgalactosamine, creating the GM3 ganglioside (4). Therefore, without the beta-hexosaminidase A enzyme, an abnormal buildup of GM2 ganglioside causes progressive damage to the nerve cells of the brain and spinal cord (1,4).
Tay-Sachs results from a mutation of the HEXA gene causes insufficient activity of the enzyme called beta-hexosaminidase A, which prevents GM2 ganglioside from breaking down in the lysosome (1). The failure to degrade the GM2 ganglioside results in the lysosome to become filled with undigested material. This accumulation is very toxic to the neurons of the brain and spinal cord, resulting in the signs and symptoms of Tay-Sachs disease (4).
The symptoms that arise in Tay-Sachs patients vary depending on the amount of activity of the beta-hexosaminidase A enzyme (2). The severity of the disease increases by the amount of enzyme is left in the body (2). There are three different forms of the disease that is discrete by age. The different forms include infantile (primary type), juvenile, and late adult-onset (rare type) (2). The symptoms between the different age of onset are quite similar. Some examples include impaired motor skills, a cherry-red spot in the eye, blindness, seizures, and neurological impairment (2). Because this is a rare disease, rendering a diagnosis can be challenging.
For a confirmed diagnosis, a physical evaluation and specialized test are performed. An enzyme screening can be done to measure the beta-hexosaminidase A enzyme levels in the blood (3). Molecular genetic testing can confirm if the patient has Tay-Sachs disease. Genetic testing can detect if the HEXA gene has any mutations that would cause the disorder (2,3). Prenatal diagnosis can be conducted by utilizing the specialized test known as Chorionic villus sampling (CVS) and amniocentesis (3). These tests involve removal of tissue from a placenta and sampling the embryonic fluid.
Tay-Sachs is inherited in an autosomal recessive manner (5). The mutation of the HEXA gene occurs on chromosome 15 (5). Children can acquire the disease if both parents are carriers of the disorder. There is a 25% chance of the child having the Tay-Sachs disease. The disease is extremely rare in the general population (1). It is most common among certain communities which include Ashkenazi Jewish, French Canadians of Quebec, Old Order Amish of Pennsylvania, and the Cajun population of Louisiana (1,3).
Tay-Sachs patients have a minimal amount of treatment options offered to them. A cure does not currently exist at the moment for this disease. The treatment used is mostly supportive and directed to provide comfort (6). Drugs are used to help with some of the symptoms. One drug that is commonly used is an anticonvulsant medicine used to control epileptic seizures (6). A feeding tube and a wheelchair may also be used to provide support and comfort. Tay-Sachs disease is progressive and is fatal typically around a young age (1). Research is still in the process in hopes of finding a cure for the disease.