Ataxia-telangiectasia is an inherited autosomal recessive disease. This means that two copies of the ATM (ataxia telangiectasia mutated) gene, located on chromosome 11, in each cell are present in A-T patients.

The disease results from mutations in a gene called ATM. The ATM gene provides codes for a protein that helps to control cell division and is involved with DNA repair. This protein plays an important role in the normal development and activity of many body systems, including the nervous system and immune system. Mutations in the ATM gene can either reduce or eliminate the function of the ATM protein.

Without this protein, cells in the brain die inappropriately, especially in the cerebellum (area of the brain that coordinates movement). Therefore, when these cells die, the patient is unable to coordinate muscle movement adequately.

Also, the mutated gene prevents cells from responding correctly to DNA damage. Instead of activating DNA repair, the gene allows genetic defects to accumulate in the body. This may cause cells to grow and divide uncontrollably, which often leads to cancer.

In most cases, the parents of an A-T patient are carriers of the disease, but do not show signs of the disorder. If both parents are carriers of the disorder, there is a 25% chance that each of their children will have the disease and a 66% chance that each child will be a carrier for the disease.

Symptoms usually develop between the ages of one and five, and they become progressively worse with age. The first signs of A-T include delayed motor skill development, poor balance and slurred speech. Telangiectasias (tiny, red "spider" veins), which appear in the corners of the eyes or on the surface of the ears and cheeks, are common characteristics of the disease.

Common symptoms include delayed walking, unsteady or jerky gait (cerebellar ataxia), dilated blood vessels in the whites of the eyes, graying of the hair, irregular pigmentation of skin that is exposed to sunlight, dilated blood vessels in the skin of the nose/ear/flexion side of the elbow/knee, decreased mental development (which slows or stops after age 10-12), movement disorder, abnormal eye movements (nystagmus) and seizures.

Complications of the disease may include severe respiratory infections, cancer, curved spine and diabetes.

General: Diagnosis is based on a person's medical history, family history and a complete neurological evaluation, which includes a magnetic resonance imaging (MRI) scan of the brain. Blood test may be performed to rule out other possible disorders that present similar symptoms. Genetic blood tests are also available to confirm a diagnosis or determine whether an individual is a carrier for the disease.

Physical examination: During a physical examination, a qualified healthcare provider may notice that the patient has a mask-like face, decreased deep tendon reflexes, skin color changes, skin rash, growth deficiency, absence of pubertal development or hypoplastic (underdeveloped) tonsil, lymph nodes and spleen.

Genetic testing: The DNA of a suspected patient may be analyzed to determine whether or not the individual has the mutated gene. This test may be performed to confirm a diagnosis or to determine whether an individual is a carrier for the disease.

Serum immunoelectrophoresis: The healthcare provider may take a blood sample to check the serum immunoglobulin levels. Individuals with A-T often have decreased immunoglobulin A (IgA) and immunoglobulin E (IgE) levels. This is because A-T causes hypoplasia of the thymus, which is associated with defective T-cell function and subsequently leads to decreased levels of circulating immunoglobulin.

X-ray: X-rays may detect a small thalamus gland, which is associated with A-T. However, A-T patients are extremely sensitive to radiation because they have an increased tendency of chromosomal breakage. A-T patients should not be exposed to radiation or X-rays unless absolutely necessary.

Imaging studies: Computerized tomography (CT) and magnetic resonance imaging (MRI) scans may show signs of cerebellar atrophy (shrinkage or wasting away). However, A-T patients are extremely sensitive to radiation because they have an increased tendency of chromosomal breakage. A-T patients should not be exposed to radiation or X-rays unless absolutely necessary.

Cancer: The mutated ATM gene prevents cells from responding correctly to DNA damage. Instead of activating DNA repair, the gene allows genetic defects to accumulate in the body. This may cause cells to grow and divide uncontrollably, which often leads to cancer.

About 20% of A-T patients develop cancer, most frequently acute lymphocytic leukemia or lymphoma. Cancer in A-T patients is often life threatening. A group of researchers reviewed 58 A-T autopsy cases and found that 21% of deaths were caused by cancer along, and 28% were caused by a combination of cancer and pulmonary infections.

Curved spine: The poor muscle control and muscle weakness associated with A-T can lead to a curved spine in some patients. Progressive scoliosis (spine that curves away from the middle or to the side) and kyphosis (curved spine that causes a bowing of the back, which leads to a hunchback or slouching posture) may develop in A-T patients.

Diabetes: A-T patients may develop diabetes during adolescence. Researchers believe that ATM plays an important role in signaling events that stimulate a cell to take in more glucose. More research is necessary to fully understand the association between A-T and diabetes.

Progressive movement disorder: In A-T patients, the cells in the brain die, especially those cells that are involved in coordinating movements (the cerebellum). When these brain cells die, the body has difficulty coordinating muscles. As the disease progresses and motor function continues to decline, the individual may eventually be limited to a wheelchair.

Pulmonary infections: Recurrent pulmonary infections are common among A-T patients because they typically have a deficiency of immunoglobulin A (IgA). In healthy individuals, IgA makes up about 90% of the globulin found in nasal secretions. Therefore, A-T patients are at an increased risk for developing pulmonary infections.

Researchers estimate that 48-81% of A-T patients suffer from recurrent pulmonary infections, which can be life threatening. A group of researchers reviewed 58 A-T autopsy cases and found that 46% of deaths were caused by pulmonary infections alone, and 28% were caused by a combination of pulmonary infections and cancer.