Tay-Sachs disease

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at October 20, 2016
StartDiseasesTay-Sachs disease

Tay-Sachs disease is a type of recessive genetic disorder that is progressive in nature. It is extremely rare in the general population. It manifests in individuals who have inherited abnormal genes from both parents. The disease may quietly pass through many generations of a family before manifesting in an affected child. Tay-Sachs results in the destruction of nerve cells located in the brain and in the spinal cord. Infantile onset is the most common type of Tay-Sachs, though the disease can also present itself in juveniles and adults.


Definition & Facts

Tay-Sachs disease is named after British ophthalmologist Waren Tay and American neurologist Bernard Sachs. In 1881 Tay became the first to describe a red spot that appears on the retina that is characteristic of the disease.

Six years later, Sachs detailed changes that occur on the cellular level with the disease. He also noticed it occurred more often in people of Ashkenazi Jewish descent than in the general population. Since then, it has been noted that the disease also has an increased prevalence in certain French-Canadian communities in Quebec, Canada and in the United States in Pennsylvania’s Old Order Amish and Louisiana’s Cajun communities.

Tay-Sachs disease develops due to a shortage of an enzyme vital to removing a fatty waste material in the body, especially in the brain and spinal cord. The lack of removal causes progressive damage to nerve cells. The most common form develops in infancy and results in death around four years of age, though other forms develop in both juveniles and adults.

Symptoms & Complaints

Infants who develop Tay-Sachs will seem to be developing normally until they reach three to six months of age. Once the disease takes hold, the child’s development will slow. Muscles will become weak, making skills such as sitting, crawling and turning over regress until they are lost. Afflicted infants will also become extremely startled by loud noises.

As Tay-Sachs advances, the child may develop vision loss, hearing loss, cognitive deficits, seizures, paralysis, and may have difficulty swallowing. They will also develop the characteristic eye abnormality of a red spot on the retina called cherry-red spot. The life expectancy of infantile onset Tay-Sachs is about four years.

The juvenile and adult forms of the disease are rarer than the infantile form and tend to have much milder symptoms. Juvenile Tay-Sachs tends to display symptoms in children between two and 10 years of age.

As the disease progresses, they will experience deterioration of both cognitive and motor skills. They will typically also develop dysarthria, spasticity, and difficulty swallowing. This deterioration will progress until the child dies, typically between five and15 years of age.

Adult onset of Tay-Sachs usually begins to display symptoms when a person is in their 30’s or 40’s. These symptoms may vary widely. They include unsteady gait, difficulty speaking, and swallowing, a decline in cognitive abilities, and spasticity. Patients may also develop psychosis or other symptoms of mental disorders. Though usually not fatal, patients may eventually have to use a wheelchair.


Tay-Sachs disease is caused by a mutation in the HEXA gene. This mutation of the recessive gene must be inherited from both parents in order to the disease to develop. While each parent is a genetic carrier, they usually develop no symptoms.

The HEXA gene provides the body with instructions to make part of the beta-hexosaminidase A enzyme. This particular enzyme is found cell structures called lysosomes and helps to break down and remove a fatty substance called GM2 (ganglioside). Mutations inhibit the ability of beta-hexosaminidase A to remove GM2 ganglioside, thus resulting in an accumulation of the substance, particularly nerve cells located in the brain and spinal cord.

This accumulation causes progressive damage to nerve cells, eventually resulting in the cell’s death. As more cells die, the condition of the patient deteriorates. These mutations occur primarily in populations that are genetically isolated from the general population.

Diagnosis & Tests

Diagnosis of Tay-Sachs disease usually begins at the primary care physician’s office after a patient presents symptoms consistent with the disease. From there, the doctor will order a test that uses an enzyme assay in order to determine the activity of beta-hexosaminidase A. Once a decrease in activity has been determined, molecular analysis is used to confirm the diagnosis. An eye examination using an ophthalmoscope can detect the cherry-red spot that all patients with infantile onset Tay-Sachs become afflicted with.

Treatment & Therapy

There is no cure available to patients with Tay-Sachs disease. Children suffering from infantile onset will most likely die around four years of age, even with the best of care. There is also no therapy regimen that can delay or reverse the progression of symptoms.

Treatment tends to be symptomatic and focuses on improving the quality of life for patients. Treatment also focuses on lowering the risk of infection in order to extend the lifespan of patients.

Infants with Tay-Sachs will most likely require a feeding tube as the ability to swallow becomes lost. Medications can be prescribed to adult onset patients in order to help control seizures and psychiatric symptoms. It was discovered in 2011 that pyrimethamine can be used to increase the activity level of beta-hexosaminidase A and slow the progression of adult onset Tay-Sachs disease.

Prevention & Prophylaxis

Because Tay-Sachs is an inherited disease, there is little that can be done to prevent its occurrence. When it is known that both parents are carriers for the disease, prenatal genetic testing can be used to determine whether the fetus has received copies of the defective genes. This testing is done through chorionic villus sampling (CVS) which is done 10-14 weeks into the pregnancy or by amniocentesis which is done between 15-18 weeks.

Couples using in vitro fertilization can have embryos tested for Tay-Sachs before implantation. Some Orthodox Jewish communities use screening programs to help couples determine risk factors. Potential parents can use a blood test to determine if they are carriers. The test is typically not given in a routine physical examination.