Ataxia telangiectasia is a rare inherited disorder that affects the nervous system, immune system, and other body systems. Affected children typically develop difficulty walking, problems with balance and hand coordination, involuntary jerking movements, muscle twitches, and disturbances in nerve function. 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. Affected individuals tend to have high amounts of a protein called alpha-fetoprotein (AFP) in their blood. People with ataxia-telangiectasia often have a weakened immune system, and many develop chronic lung infections and also have an increased risk of developing cancer, particularly cancer of blood-forming cells (leukaemia) and cancer of immune system cells (lymphoma).
A diagnosis of ataxia-telangiectasia is made based upon detailed patient history, a thorough clinical evaluation, identification of characteristic symptoms, and a variety of specialized tests including blood tests, magnetic resonance imaging (MRI), and karyotyping. Blood tests may detect elevated levels of serum alpha-fetoprotein, which occurs in approximately 85 per cent of cases. However, in unaffected children, this protein may remain elevated until 2 years of age. Blood tests may also reveal elevated liver enzymes. During an MRI, magnetic field and radio waves are used to create cross-sectional images of the brain, which can show progressive cerebellar atrophy. Karyotyping is a specialized test that detects chromosomal abnormalities. Affected individuals have an increased frequency of such chromosomal abnormalities.
Ataxia telangiectasia (A-T) is suspected whenever a child develops signs of ataxia, meaning unsteady walking. Testing of the Ataxia telangiectasia mutated (ATM) gene is available, and genetic mutations can be identified in about 90% of people with A-T. The following tests may be more helpful in determining if someone has A-T or another type of ataxia:
- Immunoblotting (ATM protein testing). This is the best test to diagnose A-T. Nearly all individuals with A-T will have very low or no amounts of the protein made by the ATM gene.
- Radiosensitivity assay. Since people with A-T have an increased sensitivity to radiation, removing some cells and treating the sample with radiation therapy can help make the diagnosis. It can take up to 3 months to get a result from this test.
- ATM kinase activity. This test looks at the activity level of the protein made by the ATM gene. Little to no activity means that there is likely a mutation in the ATM gene.
For carriers of one copy of a mutated ATM gene, early breast cancer screening may be advisable. This should be decided by a doctor who manages patients who have an increased risk for breast cancer. If cancer is detected, it is very important to seek out a doctor who is experienced in treating cancer in people who have ataxia-telangiectasia. Standard doses of some types of chemotherapy and radiation therapy may be more harmful to patients with ataxia-telangiectasia.
At this time, there are no established guidelines for cancer screening in children with ataxia-telangiectasia. The following are generally recommended:
- Yearly lab work (complete blood count, complete metabolic panel, and lactate dehydrogenase) to screen for lymphoma and leukemia.
- Yearly physical exams by a doctor who knows this condition well, giving special attention to any signs of leukemia or lymphoma (weight loss, bruising and localized pain or swelling).
- Yearly check-ups with the child’s regular pediatrician.
Diagnostic genetic testing
If the doctor or genetic counsellor suspects that a person has ataxia-telangiectasia, diagnostic testing may take place as follows:
- A blood sample is collected.
- DNA is isolated from the cells in the sample. A person’s genes are made of DNA.
- Both copies of the person’s ATM gene are checked for possible changes. A genetic specialist compares the two copies of the person’s ATM gene to normal copies of the gene. If there are differences, the specialist decides if they might cause a certain condition such as ataxia-telangiectasia.
- If a mutation is found in the ATM gene, the genetic counselor will work with the family in the following ways:
- To help the family understand the risks of ataxia-telangiectasia
- To find out if other family members should consider testing for the mutation
- To help with decisions about prenatal genetic testing
It is important to remember that genetic testing does not always find mutations in the ATM gene for all people with ataxia-telangiectasia. A person can still have ataxia-telangiectasia even if no ATM mutation is found.
Prenatal genetic testing
Parents may undergo prenatal testing to find out if the pregnancy is affected with known ATM mutations in the family. Testing may take place either before pregnancy occurs or during pregnancy.
- Testing that occurs before pregnancy — Testing that happens before pregnancy is called preimplantation genetic testing (PGT). This special type of genetic testing is done along with in vitro fertilization (IVF). PGT offers a way to test embryos for known ATM mutations before placing them into the uterus.
- Testing that occurs during pregnancy — Testing can be used to see if a pregnancy is affected with known ATM mutations. A doctor gathers cells from the pregnancy in one of two ways:
- Chorionic villus sampling (CVS) — during the first trimester (first three months)
- Amniocentesis — during the second trimester or later (last six months)
Both of these tests carry minor risks and should be discussed with an experienced doctor or genetic counsellor.
Genetic testing for ataxia-telangiectasia is a complex process. Those thinking about testing should take time to consider the benefits and risks. They should discuss the process with a genetic counsellor before testing is done.
The goal of screening is finding and treating cancer early to allow the best outcome for patients. It is possible that recommended screenings may change over time as doctors learn more about ataxia-telangiectasia. Parents should discuss all screening options for their child with a doctor who knows this condition well. Because ataxia telangiectasia is a complex condition, it is very important that parents seek out an experienced doctor for their child.