Ataxia-telangiectasia (AT) is a rare, neurodegenerative, inherited disease which affects many parts of the body and causes severe disability. Ataxia refers to poor coordination and telangiectasia to small dilated blood vessels, both of which are hallmarks of the disease. Signs and symptoms of the condition usually begin in early childhood, often before age 5. The condition is typically characterized by cerebellar ataxia (uncoordinated muscle movements), oculomotor apraxia, telangiectasias, choreoathetosis (uncontrollable movements of the limbs), a weakened immune system with frequent infections, and an increased risk of cancers such as leukemia and lymphoma.
Ataxia-telangiectasia 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.
Affected individuals tend to have high amounts of a protein called alpha-fetoprotein (AFP) in their blood. The level of this protein is usually increased in the bloodstream of pregnant women. The effect of abnormally high levels of AFP in people with ataxia-telangiectasia is unknown.
People with ataxia-telangiectasia often have a weakened immune system, and many develop chronic lung infections. They are also at an increased risk of developing cancer, particularly leukemia and lymphoma. Affected individuals are very sensitive to the effects of radiation exposure, including medical x-rays. Although people with ataxia-telangiectasia usually live into adulthood, their life expectancy is reduced.
Followings are known symptoms:
- Abnormal head movements
- Loss of balance
- Slurred speech
- Abnormal eye movements
- Poor coordination
- Trembling of extremities
- Cutaneomucosal telangiectasias
- Immunodeficiency: repeated sinus and lung infections
- Growth delay
A-T is caused by changes (mutations) in the ATM gene (11q22.3) and is inherited in an autosomal recessive manner. This gene is expressed ubiquitously and encodes a protein kintase playing a key role in the control of double-stranded breaks in DNA repair, notably in the Purkinje cells.
The diagnosis of AT is usually suspected by the combination of neurologic clinical features (ataxia, abnormal control of eye movement, and postural instability) with telangiectasia and sometimes increased infections, and confirmed by specific laboratory abnormalities (elevated alpha-fetoprotein levels, increased chromosomal breakage or cell death of white blood cells after exposure to X-rays, absence of ATM protein in white blood cells, or mutations in each of the person’s ATM genes).
A variety of laboratory abnormalities occur in most people with A-T, allowing for a tentative diagnosis to be made in the presence of typical clinical features. Not all abnormalities are seen in all patients. These abnormalities include:
- Elevated and slowly increasing alpha-fetoprotein levels in serum after 2 years of age
- Immunodeficiency with low levels of immunoglobulins (especially IgA, IgG subclasses, and IgE) and low number of lymphocytes in the blood
- Chromosomal instability (broken pieces of chromosomes)
- Increased sensitivity of cells to x-ray exposure (cells die or develop even more breaks and other damage to chromosomes)
- Cerebellar atrophy on MRI scan
The diagnosis can be confirmed in the laboratory by finding an absence or deficiency of the ATM protein in cultured blood cells, an absence or deficiency of ATM function (kinase assay), or mutations in both copies of the cell’s ATM gene. These more specialized tests are not always needed, but are particularly helpful if a child’s symptoms are atypical.
The life expectancy of people with AT is highly variable. The average is approximately 25 years, but continues to improve with advances in care. The two most common causes of death are chronic lung disease (about one-third of cases) and cancer (about one-third of cases).
There is no cure for AT and, currently, no way to slow the progression of the disease. Treatment is symptomatic and supportive. Physical and occupational therapy may help maintain flexibility. Speech therapy may also be needed. Gamma-globulin injections may be given to help supplement a weakened immune system. High-dose vitamin regimens may also be used.