Ataxia Telangiectasia Causes, Symptoms, Diagnosis, Treatment, Prevention

Ataxia Telangiectasia Causes, Symptoms, Diagnosis, Treatment, Prevention

What is Ataxia Telangiectasia?

Ataxia Telangiectasia is a rare inherited disorder that affects the nervous system, immune system, and other body systems. This disorder is characterized by progressive difficulty with coordinating movements (ataxia) beginning in early childhood, usually before age 5. Affected children typically develop difficulty walking, problems with balance and hand coordination, involuntary jerking movements (chorea), muscle twitches (myoclonus), and disturbances in nerve function (neuropathy). The movement problems typically cause people to require wheelchair assistance by adolescence. People with this disorder also have slurred speech and trouble moving their eyes to look side-to-side (oculomotor apraxia). Small clusters of enlarged blood vessels called telangiectases, which occur in the eyes and on the surface of the skin, are also characteristic of this condition.

Ataxia Telangiectasia Causes, Symptoms, Diagnosis, Treatment, Prevention

Affected individuals tend to have high amounts of a protein called alpha-fetoprotein (AFP) in their blood. The level of this protein is normally increased in the bloodstream of pregnant women, but it is unknown why individuals with Ataxia Telangiectasia have elevated AFP or what effects it has in these individuals.
People with Ataxia Telangiectasia often have a weakened immune system, and many develop chronic lung infections. They also have an increased risk of developing cancer, particularly cancer of blood-forming cells (leukemia) and cancer of immune system cells (lymphoma). Affected individuals are very sensitive to the effects of radiation exposure, including medical x-rays. The life expectancy of people with Ataxia Telangiectasia varies greatly, but affected individuals typically live into early adulthood.

Ataxia Telangiectasia is very rare, but it occurs in every population world wide, with an estimated frequency of between 1/40,000 and 1/100,000 live births. But it is believed that many Ataxia Telangiectasia cases, particularly those who die at a young age, are never properly diagnosed. Therefore, this disease may actually be much more prevalent. According to the Ataxia Telangiectasia Project Foundation, an estimated 1% (2.5 million in the United States) of the general population carries defective Ataxia Telangiectasia genes. Carriers of one copy of this gene do not develop Ataxia Telangiectasia, but have a significantly increased risk of cancer. This makes the Ataxia Telangiectasia gene one of the most important cancer-related genes identified to date.

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Causes and symptoms of Ataxia Telangiectasia

The ATM gene is autosomal recessive, meaning the disease occurs only if a defective gene is inherited from both parents. Infants with Ataxia Telangiectasia initially often appear very healthy. At around age two, ataxia and nervous system abnormalities becomes apparent. The root cause of Ataxia Telangiectasia-associated ataxia is cell death in the brain, specifically the large branching cells of the nervous system (Purkinje's cells) which are located in the cerebellum. A toddler becomes clumsy, loses balance easily and lacks muscle control. Speech becomes slurred and more difficult, and the symptoms progressively worsen. Between ages two and eight, telangiectases, or tiny, red "spider" veins, appear on the cheeks and ears and in the eyes.

How is Ataxia Telangiectasia inherited?

Normally, every cell has two copies of each gene: one inherited from the mother and one inherited from the father. Ataxia Telangiectasia follows an autosomal recessive inheritance pattern. In autosomal recessive inheritance, a mutation must be present in both copies of the gene in order for a person to be affected. This means that each parent must pass on a gene mutation for a child to be affected. A person who has only one copy of the gene mutation is called a carrier. When both parents are carriers of a recessive gene mutation, there is a 25% chance that a child will inherit two mutations and be affected with Ataxia Telangiectasia. First-degree relatives (parents, brothers, sisters, and children of a person with Ataxia Telangiectasia) have a 50% chance of inheriting the single gene mutation and becoming a carrier. 

Options exist for couples interested in having a child when they know that one of them carries a gene mutation that increases the risk for this hereditary cancer syndrome. Preimplantation Genetic Diagnosis (PGD) is a medical procedure done in conjunction with in-vitro fertilization (IVF). It allows people who carry a specific known genetic mutation to have children who do not carry the mutation. A woman’s eggs are removed and fertilized in a laboratory. When the embryos reach a certain size, one cell is removed and is tested for the hereditary condition in question. The parents can then choose to transfer embryos which do not have the mutation. PGD has been in use for over a decade, and more recently has been used for several hereditary cancer predisposition syndromes.  For more information, talk with an assisted reproduction specialist at a fertility clinic.

Is there any treatment?

There is no cure for Ataxia Telangiectasia and, currently, no way to slow the progression of the disease. Treatment is symptomatic and supportive. Physical and occupational therapy help to maintain flexibility. Speech therapy is important, teaching children to control air flow to the vocal cords. Gamma-globulin injections may be useful if immunoglobulin levels are sufficiently reduced to weaken the immune system. High-dose vitamin regimens and antioxidants such as alpha lipoic acid also may also be used.

Prevention for Ataxia Telangiectasia

Prevention of ataxia telangiectasia begins before pregnancy and birth. It calls for knowing whether both the man and the woman conceiving a child are carriers of the defective gene responsible for the disease. If someone in your family has ataxia telangiectasia, you and your partner might consider genetic counseling to determine if you're carriers of the ATM gene before you decide to become pregnant. Genetic testing can determine whether this gene is present in your DNA.

Ataxia telangiectasia develops only when a person gets a copy of the ATM gene from both parents. So if neither of you or only one of you has the ATM gene, you'll know that your children won't have ataxia telangiectasia. However, if you both carry the defective gene, each child you conceive will have a one-in-four chance of developing the disease and you may want to discuss further options with your doctor.

What are the estimated cancer risks associated with being a carrier or heterozygote for an Ataxia Telangiectasia gene mutation?

Carriers (people with one ATM gene mutation) also seem to have an increased risk of developing breast cancer. Some studies have shown a five to nine times higher lifetime risk for breast cancer for women who are carriers, while other studies have shown two times the lifetime risk of developing breast cancer compared to the general population. There is some data suggesting that these individuals may also be at an increased risk for colon and/or stomach cancer but this isn’t entirely clear.

Additional research is needed to clarify the cancer risk for ATM mutation carriers. Studies also show that carriers may have an increased risk of heart disease.

How do I know if I'm a carrier?

In the past, carriers were identified mainly because they were parents of a child with Ataxia Telangiectasia. With the cloning of the ATM gene, however, physicians or cancer genetics professionals can now conduct genetic testing, analyzing patients' DNA to look for Ataxia Telangiectasia mutations in the ATM gene. The genetic testing is complex and difficult, however; definitive results may not be possible. 

One of the most helpful laboratory tests used to assist in the diagnosis of Ataxia Telangiectasia is the measurement of "fetal proteins," or serum alpha-fetoprotein, in the blood. These are proteins that are usually produced during fetal development but may persist at high levels in some conditions (such as Ataxia Telangiectasia) after birth. The vast majority of Ataxia Telangiectasia patients (more than 95 percent) have elevated levels of serum alpha-fetoprotein. When other causes of elevations of alpha-fetoprotein are eliminated, elevated alpha-fetoprotein in the blood, in association with the characteristic signs and symptoms, makes the diagnosis of Ataxia Telangiectasia a virtual certainty.

What is the prognosis?

Average lifespan has been improving for years, for unknown reasons, and varies with the severity of the underlying mutations, ATM (Ataxia Telangiectasia mutated) protein levels, and residual ATM kinase activity. Some individuals with later onset of disease and slower progression survive into their 50s.