Tay-Sachs Disease

Topic Overview

What is Tay-Sachs disease?

Tay-Sachs disease is a rare genetic disorder in which little or no hexosaminidase A (hex A) enzyme is produced by the body. Hex A is necessary to break down normal fatty compounds (called gangliosides) in the body cells. When these fatty compounds are not broken down, they gradually accumulate and damage brain and nerve cells, making the cells unable to function properly.

There are two forms of Tay-Sachs disease:

• In the classical or infantile form (the most common type), the body produces no hex A. This form of the disease develops during infancy.
• In late-onset Tay-Sachs (LOTS), the body produces some hex A, but lower-than-normal amounts. This form of the disease begins between adolescence and the mid-30s.

The Tay-Sachs gene is most common in people of Ashkenazi Jewish descent. About 1 out of 30 people in this population is a carrier of the disease.^{1, 2} People of French-Canadian descent from the East Saint Lawrence River Valley of Quebec and people of Cajun descent in Louisiana are also at a higher risk than the general population.

What causes Tay-Sachs disease?

Tay-Sachs disease is an autosomal recessive disease. If you inherit from both parents a changed (mutated) gene that can cause Tay-Sachs, you will get the disease. If you inherit the gene from only one parent, you are a carrier, meaning that you carry the gene for Tay-Sachs but do not get the disease.

• To inherit the classical or infantile form, you must inherit from both parents the gene that cannot produce hex A (inactive hex A gene).
• In late-onset Tay-Sachs disease (LOTS), the hex A gene is altered so that it produces a small amount of hex A. If you have LOTS, you inherited two late-onset hex A genes or one late-onset and one inactive gene.

What are the symptoms?

A baby with Tay-Sachs disease appears healthy at birth. Symptoms usually first appear 3 to 6 months after birth, beginning with mild motor weakness and occasional twitches of the eye (myoclonic jerks). By 6 to 10 months of age, the baby's motor skills may be lost. After this, the disease progresses rapidly to seizures, blindness, paralysis, and death at age 4 to 5.

In late-onset Tay-Sachs (LOTS), the symptoms may be subtle (such as clumsiness or mood changes) and go unnoticed at first. Later symptoms may include muscle weakness and twitching, slurred speech, impaired thinking and reasoning, and mental disorders. The life expectancy for a person with LOTS is not known because this condition has only recently been recognized. Depending on the severity of the symptoms, the person may live as long as someone who does not have Tay-Sachs disease.

How is Tay-Sachs disease diagnosed?

A physical exam and a blood test to measure the level of hex A is used to diagnose Tay-Sachs disease. A positive Tay-Sachs screen blood test may need to be confirmed with other genetic tests.

How is it treated?

Treatment for Tay-Sachs disease focuses on controlling symptoms and preparing for the course of the disease. There is no cure for Tay-Sachs disease. Additional personal and family support measures may be needed as the disease progresses.

How can Tay-Sachs disease be prevented?

If either you or your partner is Ashkenazi Jew or of French-Canadian or Cajun descent or has a family history of Tay-Sachs disease, that person needs to be tested to see if he or she is a carrier. If that person tests positive, the partner also needs to be tested. If both of you test positive, you should consider genetic counseling before having children.

Frequently Asked Questions

Symptoms

A baby with Tay-Sachs disease has no signs or symptoms of the disease at birth. Symptoms usually appear 3 to 6 months after birth. The symptoms are caused by damage to the brain and nerve cells from the buildup of fatty compounds. An early sign of the infantile form of Tay-Sachs is a red spot on the retina. See a picture of the retina .

Watch for the following symptoms if you suspect your baby may have Tay-Sachs disease.

At 3 to 6 months, you may notice:

• Decreased eye contact.
• Twitchy eyes (myoclonic jerks).
• Difficulty focusing on objects.
• Excessive startling by sharp but not necessarily loud noises.

At 6 to 10 months, you may notice:

• Limp and floppy muscles (hypotonia).
• Decreased alertness and playfulness.
• Difficulty sitting up or rolling over and a loss of motor skills.
• Decreased hearing and eventual deafness.
• Gradual loss of vision.
• An abnormal increase in head size (macrocephaly).

10 months and older

As a child with Tay-Sachs grows older, he or she may become blind, mentally retarded, paralyzed, and unresponsive to the environment. The child also may have seizures, difficulty swallowing, and difficulty breathing. Children with Tay-Sachs disease rarely live beyond 4 or 5 years of age.

Late-onset Tay-Sachs disease

Symptoms of late-onset Tay-Sachs disease (LOTS) usually develop between adolescence and the mid-30s. The symptoms vary among individuals, depending on the amount of hex A being produced by the body. At first, symptoms such as clumsiness or mood changes are subtle and may go unnoticed. Other symptoms that may develop include:

• Personality changes.
• Muscle weakness or twitching.
• Slurred speech.
• Impaired thinking and reasoning ability, such as memory problems, difficulty with comprehension, and short attention span.
• Inability to distinguish between what's real and unreal (psychotic episodes) or depression.

Exams and Tests

If your baby is suspected of having Tay-Sachs disease, a physical examination may reveal or confirm symptoms of the disease. A blood test (Tay-Sachs screen test) can determine whether your baby's body is producing the enzyme hexosaminidase A (hex A). The blood sample can be taken from a vein or from the umbilical cord immediately after birth.

If you are pregnant and are at risk for having a child with Tay-Sachs disease, the Tay-Sachs screen test can be done. A blood sample is collected from the placenta during chorionic villus sampling, or a sample of amniotic fluid is collected during amniocentesis. For more information, see the topics Amniocentesis and Chorionic Villus Sampling.

The Tay-Sachs screen test is also used to confirm late-onset Tay-Sachs disease in a teen or adult with symptoms of the disease.

A positive Tay-Sachs test may need to be confirmed with other genetic tests. For more information, see the medical test Genetic Test.

Screening for carriers

Knowing whether you are a carrier of Tay-Sachs disease is important because Tay-Sachs is an autosomal recessive disease. You have one gene that produces hex A and one that does not produce this enzyme. Your body probably makes about half of the normal level of hex A, which prevents you from getting the disease. But you can pass the gene on to your children. If both you and your partner are carriers, there is a 1-in-4 chance (25%) that any child you have will have Tay-Sachs disease.

If you are considering having a child, the American College of Obstetricians and Gynecologists (ACOG) recommends that:³

• Both prospective parents be screened if both of you are Ashkenazi Jews or of French-Canadian or Cajun descent or have a family history of the disease. If both of you test positive as carriers, you should consider genetic counseling.
• You or your partner be screened if either of you is an Ashkenazi Jew or of French-Canadian or Cajun descent or has a family history of the disease. If one of you tests positive for being a carrier, the other partner should be screened.

Either hex A testing or DNA testing can be done.

In Ashkenazi Jews:³

• DNA testing detects 94 out 100 carriers.
• Hex A testing detects 98 out of 100 carriers.

Treatment Overview

Treatment is aimed at controlling symptoms. For example, your child may take medicine for seizures. There is no cure for Tay-Sachs disease.

Treatment for classical or infantile Tay-Sachs disease

If your baby has Tay-Sachs disease, other support measures may be needed as the disease progresses, such as:

• Family counseling to help family members cope with the disease and prepare for the loss of the child. For more information, see the topic Grief and Grieving.
• Help with the child's care (respite care or home health care) as the child's condition gets worse.
• A support group to share experiences with other families who are dealing with Tay-Sachs disease.

Treatment for late-onset Tay-Sachs disease

Treatment for late-onset Tay-Sachs disease (LOTS) also focuses on controlling symptoms. This form of the disease was recognized only recently, so not much is known about its course. But it is known that the nervous system effects get progressively worse over time. The treatment you receive, such as medicine for depression, depends on the symptoms you have.

You may need individual counseling to help control any behavioral or mental disorders that develop. Your family may need family counseling to cope with the disease and its effects. Although you may live as long as other people who do not have Tay-Sachs disease, you still need to have a living will and durable power of attorney. For more information, see the topic Care at the End of Life.

What To Think About

An animal study has used gene transfer to put hex A enzyme in the brain so it will move to the rest of the body where it is needed.⁴ Although preliminary, this study and other studies may offer future hope for Tay-Sachs disease treatment. Talk to your doctor for information about clinical trials and other research taking place.

Home Treatment

Home treatment for Tay-Sachs disease consists of providing comfort and preparing for the course the disease will take.

If your child has Tay-Sachs disease, talk with your doctor about:

• Your concerns and the guidance you need to deal with your child.
• Whether there is a support group in your area. Talking with other families dealing with Tay-Sachs disease may be very helpful.
• The chances that a child you have in the future will have the disease. You and your spouse may need genetic counseling.
• Family counseling to help each member deal with the effects of the disease.

As your child with Tay-Sachs disease progressively gets worse, he or she will require increasing care. Encourage your child to be as active as possible for as long as possible. Give your child the love and affection you would give to any child. Your child will be as responsive and active as his or her mental and physical ability allows.

Some families find that they cannot care for their child at home without help. Talk with your doctor about options in your community, such as respite care and other home health services that help families care for their loved ones at home.

As the disease progresses, it is important that you allow yourself to grieve. For more information, see the topic Grief and Grieving.

Late-onset Tay-Sachs disease

If you have late-onset Tay-Sachs disease (LOTS), you may need individual counseling to control any behavioral or mental disorders that you develop. You and your family may need family counseling to deal with the effects of the disease. It probably will be hard to find a support group in your area, but talk with your doctor about organizations, local agencies, and Internet resources that may be helpful for you and your family.

Although you may live as long as other people who do not have Tay-Sachs disease, you still need to have a living will and durable power of attorney. For more information, see the topic Care at the End of Life.

Other Places To Get Help

Online Resource

Organizations

Related Information

• Ashkenazi Jewish Genetic Panel (AJGP)
• Genetics
• Grief and Grieving

References

Citations

1. Vallance H, Ford J (2003). Carrier testing for autosomal-recessive disorders. Clinical Laboratory Sciences, 40(4): 473-497.

2. Committee on Genetics, American College of Obstetricians and Gynecologists (2004). Prenatal and preconceptional carrier screening for genetic diseases in individuals of Eastern European Jewish descent. Obstetrics and Gynecology, 104(2): 425-428.

3. Committee on Genetics, American College of Obstetricians and Gynecologists (2005, reaffirmed 2007). Screening for Tay-Sachs disease. Obstetrics and Gynecology, 106(4): 893-894.

4. Martino S, et al. (2005). A direct gene transfer strategy via brain internal capsule reverses the biochemical defect in Tay-Sachs disease. Human Molecular Genetics, 14(15): 2113-2123.

Other Works Consulted

• Haslam RHA (2006). Degenerative diseases of the central nervous system. In FD Burg et al., eds., Current Pediatric Therapy, 18th ed., pp. 388-392. Philadelphia: Saunders Elsevier.

• Neudorfer O, Kolodny EH (2004). Late-onset Tay-Sachs disease. Israel Medical Association Journal, 6: 107-111.

• Ropper AH , Brown RH (2005). The inherited metabolic diseases of the nervous system. In Adams and Victor's Principles of Neurology, 8th ed., pp. 797-849. New York: McGraw-Hill.

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