Tay-Sachs disease is a severe progressive disorder that causes deterioration of the central nervous system, resulting in poor muscle tone, loss of motor skills, seizures, blindness, and difficulties with swallowing and breathing. On eye exam, people with Tay-Sachs disease have an unusual appearance to the retina, known as a cherry-red spot. Children born with Tay-Sachs disease appear normal at birth, however symptoms begin as early as 3 months of age and death usually occurs by age 4. There is no cure for Tay-Sachs disease.

Tay-Sachs disease is caused by the absence or near-absence of an enzyme called Hexosaminidase A (Hex A). Without this necessary enzyme, a substance called GM2 ganglioside builds up in the brain and in other cells in the body. This accumulation results in the physical and developmental features of Tay-Sachs disease.

Another more rare form of Tay-Sachs disease, known as Late-Onset Tay-Sachs disease, occurs when there is a small amount (5-15%) of Hex A present. Symptoms of Late-Onset Tay-Sachs disease typically appear between adolescence and the mid-30s and are highly variable. They can include muscle weakness and wasting, unsteady gait, hand tremors, difficult speech, and psychiatric illness.

One in 30 people with Ashkenazi Jewish ancestry is a carrier of Tay-Sachs disease. Because of the high carrier rate, the American College of Medical Genetics (ACMG) and the American College of Obstetrics and Gynecology (ACOG) recommend screening for Ashkenazi Jewish individuals. ACOG recommends that couples in which only one member is Ashkenazi Jewish also consider carrier testing for Tay-Sachs disease.

The carrier frequency of Tay-Sachs disease in non-Jewish Caucasians is around 1 in 300, with the exception of people with French-Canadian and Cajun backgrounds, in whom the Tay-Sachs carrier rate is thought to be similar to that of the Ashkenazi Jewish population (about 1 in 30). ACOG also recommends Tay-Sachs carrier screening for people of French-Canadian and Cajun ancestry.

The carrier frequency of Tay-Sachs disease in the Irish population is also increased over that of the general population and may be as high as 1 in 41.

How Is Tay-Sachs Disease Inherited?

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When there is a change in a gene (called a mutation) the instructions it contains are no longer correct and the gene cannot carry out its function. Individuals with Tay-Sachs disease have two copies of a mutation, one copy inherited from each parent. Neither gene in the pair is working correctly, which causes the symptoms of the disease.

People with Infantile Tay-Sachs disease have two mutations that cause infantile disease. Individuals with Late-Onset Tay-Sachs disease have two mutations that cause adult-onset disease, or one infantile mutation and one adult-onset mutation.

A carrier of Tay-Sachs disease is a person who has a mutation in one gene of the pair. Carriers are unaffected with the disease because the properly working gene is able to compensate for the gene that contains the mutation.

When two parents are carriers of Tay-Sachs disease:

• there is a 1 in 4 (25%) chance of having a child with Tay-Sachs disease,
• there is a 1 in 2 (50%) chance of having a child who is an unaffected carrier like the parents,
• and, there is 1 in 4 (25%) chance of having a child who is unaffected and is not carrier.

When one parent is a carrier of Tay-Sachs disease and the other parent is not a carrier, they are not at increased risk to have a child with Tay-Sachs disease. Instead, there is a 1 in 2 (50%) chance of having a child who is an unaffected carrier like the one parent.

What This Test Tells You

This test tells whether you are a carrier for Tay-Sachs disease by testing both the enzyme (Hex A) and the DNA (the HEXA gene). The combination of these two methods is considered to be the most accurate way to screen for Tay-Sachs disease.

The enzyme analysis detects about 98% of Tay-Sachs carriers. It looks to see how much of the enzyme is functioning. For example, carriers of Tay Sachs have about half as much working enzyme as non-carriers.

DNA testing detects about 95% of mutations for Tay-Sachs disease in the Ashkenazi Jewish population, 80% of mutations in the French Canadian population, and 25% of mutations in the non-Jewish Caucasian population. It looks for the seven most common gene changes or mutations that account for 90-95% of Ashkenazi Jewish carriers.

How Testing Works

Testing with DNA Direct is quick, convenient, and can be done in the privacy of your home. It can also be anonymous if you wish. How to order online and consult with our genetic experts: DNA Direct's Expert Services