What is Tay-Sachs disease?
Tay-Sachs is a very rare disease of the nervous system. Symptoms usually start during infancy or in early childhood, and become progressively worse over time. People with Tay-Sachs have a mutation in a gene that makes an important enzyme called hexosaminidase A (or HEXA for short). This altered gene causes waste material to build up in nerve cells, which damages the cells. Different mutations cause different effects on enzyme activity. The amount of remaining enzyme activity dictates the severity of disease. With lower enzyme activity, the waste builds up faster. The damage leads to problems of the nervous system, such as seizures and the loss of vision. There are three common forms of Tay-Sachs disease:
Infants with Tay-Sachs appear normal at birth. They live without problems until they are between 3 and 6 months old. The first symptoms usually include muscle weakness and some muscle twitching. Loud noises may startle an infant with Tay-Sachs more than you might expect, causing the baby to cry. As these infants grow, they are less able to perform normal activities for their age and they become less interactive. Infants may develop seizures and experience vision loss by the end of their first year. They become deaf and unable to swallow, and their muscles weaken, eventually leading to paralysis. Most do not survive beyond the toddler years.
A less severe form of Tay-Sachs starts during childhood (usually between ages 2 and 10). Children with this type of disease can develop normally through their toddler years. As young children, however, they start to develop problems with body coordination and the muscles that control speech. As in the case of infants with Tay Sachs, these children also may develop seizures and vision problems. Unfortunately, although the symptoms might come later than those of infantile Tay-Sachs and some children survive into their teen years, death usually occurs in the late teen years.
Chronic and Adult-Onset
Much rarer than infantile Tay-Sachs, the chronic and adult-onset forms of the disease start later and develop more slowly. These forms are associated with numerous neurological problems, such as poor coordination, movement disorders, speech problems and sometimes mental illness. Because the buildup of waste material in brain cells is more gradual, the brain’s ability to function may be preserved for many years.
How common is Tay-Sachs disease?
Tay-Sachs is very rare. Each year, about a dozen cases of Tay-Sachs are diagnosed in the United States, most of the infantile form. Tay-Sachs can affect people from any ethnic group, but people whose ancestors are Ashkenazi Jews have the highest likelihood of being carriers. Jewish leaders have made a point of educating people about the risks. Before this education started in the 1970s, Tay-Sachs affected about one in 3,600 children of Ashkenazi Jewish descent. Today, the rate has gone down in this group by more than 90 percent. In fact, it is now more common for the parents of a child with Tay-Sachs to be non-Jewish.
About 3 percent of people of Ashkenazi Jewish descent carry the Tay-Sachs gene. Some non-Jewish groups of people have high carrier rates, including people whose ancestors were French-Canadian, from the Louisiana bayou, or from Amish populations in Pennsylvania.
Who is at risk for Tay-Sachs disease?
Tay-Sachs disease is a result of changes in the hexosaminidase A gene (HEXA). Every child inherits two HEXA genes — one from each parent. If a child inherits one normal gene and one altered gene, the child will not develop Tay-Sachs because the one normal gene is enough to avoid the buildup of waste in the cells. (This child will be a carrier of the altered gene, however, and can pass the gene on to his or her children.)
If the child inherits two altered copies of the HEXA gene — one from each parent — the child will get Tay-Sachs disease.
It is very unusual for two people to be Tay-Sachs carriers if neither parent is of Ashkenazi Jewish descent or from another high-risk group. If you’re not in one of these high-risk groups, it’s not likely that your doctor would offer you the test.
Is there a cure?
No. Tay-Sachs is a progressive disease without a cure.
The Gene For Tay-Sachs Disease
What goes wrong with this gene?
The gene for Tay-Sachs disease tells the body how to make a protein (enzyme) called hexosaminidase A. When the amount of this enzyme is decreased, or when the enzyme is not working properly, waste products build up inside the body’s cells. This causes damage to organs such as the liver, eyes and brain.
Changes happen in different parts of the HEXA gene. Changes in one part can cause the enzyme to be totally shut off. Changes in another part might only cause a decrease in the amount of enzyme made. Other changes can cause a poorly functioning enzyme. This explains why some people get the severe form of the disease (from having no enzyme) while some get the later-onset forms (because they have some enzyme, but not enough to break down all of the waste products).
In other words, there is a threshold for the amount of enzyme. If you are below it, you can’t compensate for the waste. If you’re above it (like a carrier) you won’t get the disease.
Should You Be Tested?
Is my ethnic background the key to my risk?
Your chances of being a Tay-Sachs carrier depend on your family’s ethnic background. The American College of Obstetrics and Gynecology recommends a test called an enzyme-activity test, used to detect Tay-Sachs carriers, if one or both partners are from a high-risk group such as Ashkenazi Jewish, French-Canadian, Cajun or Amish. If only one partner is from a high-risk group, that person should be tested first. If the woman is already pregnant, it may be necessary to test both partners right away to avoid any delays.
Understanding Test Results and Options
How Do You Make Sense Of The Results?
If I test positive, what does that mean for me and my family?
Tay-Sachs testing can confirm a diagnosis in a child who has symptoms of the disease or test whether a person who has no symptoms is a carrier.
The first step is the enzyme-activity test. Lower enzyme activity usually means a person has worse symptoms. Infants with the disease tend to have no enzyme activity at all. People with the juvenile and chronic forms of Tay-Sachs tend to have low enzyme activity.
If enzyme activity is low, the DNA test can help determine the exact change in the gene. If a DNA mutation is identified in one family member, then other family members can be screened by DNA testing. Otherwise, they should be screened by the enzyme-activity test.
If your biological child has Tay-Sachs, you and your partner are both carriers of the altered HEXA gene. Carriers do not have the disease; they have one normal copy of the gene and one altered copy. You only need one “working” copy to have the enzyme activity you need. If you’re a carrier, one or both of your parents must have been a carrier too. This means your brothers and sisters have at least a 50-percent chance of having inherited the gene from one of your parents.
Could I get a positive test result, but not carry the disease gene (a false positive)?
This is a tricky question. Some people may have a Tay-Sachs mutation called “pseudo-deficiency,” a fancy way of saying, “it looks like your enzyme isn’t working, but it really is.”
Enzyme activity is about 50 percent of normal in Tay-Sachs carriers. For people with pseudo-deficiency, enzyme activity is lower. In the case of infantile Tay-Sachs, the enzyme activity is often zero. This can happen because mutations in one part of the gene can make an enzyme that’s totally inactive (true deficiency). Other mutations make a weak enzyme that’s still effective enough that you don’t get the disease (pseudo-deficiency).
This is one reason why a test that shows low enzyme activity is followed by a DNA test. If the DNA test shows you have the pseudo-deficiency, you would not have an affected child. This is true even if your partner carries the Tay-Sachs mutation. People who have one nonworking gene plus one pseudo-deficiency gene have lived into their 60s without having any symptoms.
Could I get a negative test result, but actually have the disease (a false negative)?
The enzyme activity test for Tay-Sachs detects about 97 percent of carriers. If you took the test, you would have, at most, a 3 percent chance of receiving a false negative result.
Depending on which DNA test you are offered, there may be a higher chance of missing someone who either has the disease or is a carrier. The most common type of DNA test – called “targeted mutation analysis” – only recognizes the most common mutations in the HEXA gene; it does not recognize every possible mutation. For example, certain mutations are more common among people of Ashkenazi Jewish descent. The targeted DNA test detects about 92 percent of Tay-Sachs carriers among people of Ashkenazi Jewish descent, but is less effective for other individuals.
If you or your ancestors are French-Canadian, you would want to make sure the DNA test looks for a gene deletion that occurs more frequently in French-Canadians.
Some labs are now offering a more extensive full gene sequencing test that will find 99% of mutations in any ethnic group. This test would be useful if you are not Ashkenazi Jewish, or if you know your partner is a carrier and you want the highest chance of finding a change in your gene before you plan a pregnancy.
How will I cope if the test shows I am a Tay-Sachs carrier?
Simply being a carrier has no impact on your health. Your children, however, could inherit the Tay-Sachs gene.
If I have the Tay-Sachs gene, can I have children who don’t have the gene?
Yes, but you need to “do the math” to understand the risks of passing on the mutated gene.
If you’re a Tay-Sachs carrier and your partner is not, you have a 50-percent chance of passing the gene to each child. Even if your child inherits your copy of the Tay-Sachs gene, the child will NOT have Tay-Sachs, but simply will be a carrier, like you.
If you and your partner are both Tay-Sachs carriers, your child has a:
- 25-percent chance of inheriting Tay-Sachs (two copies of the Tay-Sachs gene)
- 50-percent chance of being a carrier (one Tay-Sachs gene and one normal gene)
- 25-percent chance of not being a carrier (two normal genes)
Someone with the chronic or adult-onset form of the disease may have children. Since a person with Tay-Sachs has an alteration in both copies of their HEXA gene, their children would have a 100-percent chance of receiving a Tay-Sachs gene. However, whether or not the child gets the disease will depend on the other parent. If the other parent was a Tay-Sachs carrier, the child would have a 50-percent chance of inheriting the disease.
Of more than 100 HEXA mutations known, more than 70 are associated with the infantile form of Tay-Sachs. There are also several mutations associated with the chronic form.
During pregnancy, can I determine the risk my baby has of developing Tay-Sachs?
To discover whether your unborn child has inherited Tay-Sachs, you and your partner can seek prenatal testing. Early in the pregnancy, a doctor can use either chorionic villus sampling or amniocentesis to get a sample of tissue from the fetus. A lab then tests the tissue to determine if the fetus has inherited the disease.
Be sure to talk with your obstetrician or a genetic counselor about your options.
If I DON’T have the Tay-Sachs gene, can I have children who DO have the gene?
If you’re not a carrier, your children cannot inherit the gene from you. They could still get the gene from your partner if he or she is a carrier, but they would not get Tay-Sachs disease because they would only have one altered gene.
Is there any harm in finding out if I carry the gene?
Carrying the gene has no health implications. You may, however, feel upset if you learn that you carry a gene that could potentially cause a disease in your future children.
How does the test work?
There are two types of tests for Tay-Sachs. Both require a blood sample:
The enzyme-activity test checks how well the HEXA enzyme is working. Anyone with Tay-Sachs symptoms or who wants to know if he or she is a possible carrier should start with the enzyme test. If this test comes back normal, you’re not a carrier (with about 97 percent certainty). If the activity test is abnormal, you will need to get the DNA test.
Enzyme testing of women who are already pregnant, or who are taking oral contraceptives, must be done on leukocytes (white blood cells) rather than serum. Enzyme testing of serum can give false positive results.
The DNA test is important because two people with a HEXA mutation might not have the same gene mutation. Different combinations of mutations in a child can affect how severe the symptoms are.
More than 100 different mutations of the HEXA gene exist. Most mutations cause the severe form of Tay-Sachs, but some cause the later-onset forms or the pseudo-deficiency. For routine testing, most commercial labs only do the DNA test for the six most common mutations. If you only get the targeted mutation DNA test, and you have one of the less common mutations, you will get a false negative. The less common mutations still cause a decrease in enzyme activity, so they show up on the enzyme-activity test. If your enzyme test was abnormal, then your doctor can have your testing done at a lab that performs full gene sequencing to look for the less common mutations.
Enzyme analysis should be performed before full gene sequencing.
What does the test cost?
The enzyme activity test costs about $130. The DNA test for targeted mutations costs about $225. The full gene sequencing costs about $1,700. Costs vary depending upon the lab doing the testing.
Does insurance pay for the test?
Most health-insurance companies pay 80 percent or more of the cost. Some companies pay all the cost; others won’t pay any portion. If you are considering this test, call your insurance company and ask about its coverage.
How long does it take to get results?
Once you have blood drawn, you will receive results in two to three weeks. The full gene sequencing can take two to four weeks. The laboratory sends the results to the medical center that ordered the test. You need to return to the center to learn your results.
Can a health-insurance company raise my rates or drop my coverage if I test positive?
In 2008, the U.S. government passed a law called GINA (Genetic Information Nondiscrimination Act). The law prohibits discrimination by health insurers and employers on the basis of genetic information. Learn more here.
The Federal Health Insurance Portability and Accountability Act (HIPAA) of 1996 also prohibits health-insurance discrimination based on any “health status-related factor,” (including genetic information) by group health plans. People with group insurance are usually covered by HIPAA, while people who are self-employed are covered only by state laws.
Some states have enacted legislation to cover the gaps. Thirty-four states prohibit health-insurance companies from using genetic information to deny coverage. Other states require specific justification for the use of genetic information in denying a claim. Texas bans the use of genetic information by any group health plans, and Alabama prohibits discrimination based upon predisposition to cancer.
Life insurance, long-term care and disability insurance are generally not covered by these laws. People with life and disability coverage provided by their employers are unlikely to have this insurance affected by a genetic test result.