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Primary Immunodeficiency Diseases
Definition  |  Clinical Presentation  |  Diagnosis  |  Inheritance  |  General Treatment  |  Specific Therapy  |  Expectations

Ataxia - Telangiectasia

Ataxia-Telangiectasia is a primary immune deficiency disease that affects a number of different organs in the body. Patients with Ataxia-Telangiectasia have an unsteady gait (Ataxia), dilated blood vessels (Telangiectasia), and a variable immunodeficiency involving both B-lymphocytes and T-lymphocytes.


Definition

Ataxia-Telangiectasia (AT) is a primary immunodeficiency disease which affects a number of different organs in the body. It is characterized by:

  1. Neurologic abnormalities resulting in an unsteady gait (ataxia).
  2. Dilated blood vessels (telangiectasia) of the eyes and skin.
  3. A variable immunodeficiency involving both cellular (T-lymphocyte) and humoral (B-lymphocytes) immune responses.
  4. A predisposition to certain kinds of cancer.

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Clinical Presentation

The first presenting symptom is generally ataxia, a medical term used to describe an unsteady gait. Children with Ataxia-Telangiectasia (AT) may sway when they stand or sit, and they wobble or stagger when they walk. It usually results from neurologic abnormalities affecting a part of the brain (the cerebellum) that controls balance. AT first becomes apparent when the child begins to walk, typically between 12 and 18 months of age. At this early point in time, many children are thought to have cerebral palsy or an undefined neurologic disorder. The specific diagnosis of AT may be difficult to make when symptoms first appear. Later neurological symptoms include abnormalities in eye movements, including rapidly alternating twitches of the eyes (nystagmus) and difficulty in initiating voluntary eye movements (oculomotor apraxia). They also develop difficulty using the muscles needed for speech (dysarthria) and swallowing.

Dilated blood vessels (telangiectasia) become apparent after the onset of the ataxia, generally between 2 and 8 years of age. Telangiectasias usually occur on the white portion of the eye (bulbar con-junctiva) but may also be found on the ears, neck and extremities.

Another clinical feature of AT is an increased susceptibility to infections. This symptom is a major feature in some individuals. Infections most commonly involve the lungs and sinuses, and are usually caused by bacteria or viruses. The infections are, at least in part, due to the variable immunodeficiency seen in AT. Another factor that may contribute to lung infections is the swallowing dysfunction that results in aspiration with solid food and liquid going down the passageway to the lungs (the trachea) instead of the passageway to the stomach (the esophagus).

Patients with AT may have defects in both their T-lymphocyte system and B-lymphocyte system. They may have reduced numbers of T-lymphocytes in their blood. These abnormalities in T-lymphocytes are usually associated with a small or immature thymus gland. The low number of T-lymphocytes does not always increase the patient's susceptibility to infection. Most patients with AT produce some antibody responses against foreign antigens, such as microorganisms, but some of these responses may be impaired, particularly those responses directed against the large sugar molecules (polysaccharides) found on the outside of the bacteria that cause respiratory infections. These disordered antibody responses may be associated with abnormal immunoglobulin levels - absent IgA in 70% of patients, absent IgE in 80%. IgG subclass deficiencies may also be found in some individuals with AT.

Finally, patients with AT have an increased risk for developing certain cancers, particularly cancers of the immune system, such as lymphoma and leukemia.

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Diagnosis

The diagnosis of Ataxia-Telangiectasia (AT) is usually based on characteristic clinical findings and supported by laboratory tests. Once all of the clinical signs and symptoms of AT have become obvious in an older child or young adult, the diagnosis is relatively easy. The most difficult time to diagnose AT is during the period when neurologic symptoms are first apparent (early child-hood) and the typical telangiectasias have not yet appeared. During this period, a history of recurrent infections and typical immunologic findings can be suggestive of the diagnosis. One of the most helpful laboratory tests used to assist in the diagnosis of AT is the measurement of "fetal proteins" in the blood. These are proteins that are usually produced during fetal development but may persist at high blood levels in some conditions (such as AT) after birth. The vast majority of AT patients (>95%) 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 AT a virtual certainty.

Individuals with AT may also have an increased frequency of spontaneous breaks in their chromosomes as well as an increased frequency of chromosomal rearrangements. These abnormalities often occur in the vicinity of genes essential for lymphocyte function, such as immunoglobulin and T-lymphocyte antigen receptor genes. The frequency of chromosomal breaks is increased when T-lymphocytes are exposed to X-rays in the laboratory, and this forms them basis for a specialized diagnostic test for AT.

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Inheritance

Ataxia-Telangiectasia (AT) is inherited as an autosomal recessive disorder. The gene responsible for AT has been identified and is found on the long arm of chromosome 11 at 11q22-23. It controls the production of a phosphatidylinositol - 3 -kinase - like enzyme involved in cellular responses and cell cycle control. The identification of the specific gene responsible for AT has made carrier detection and prenatal diagnosis possible, though it is not yet available in commercial laboratories.

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General Treatment

There is as yet no cure for any of the problems in Ataxia-Telangiectasia (AT), and treatment is largely supportive. Patients should be encouraged to participate in as many activities as possible. Children should be encouraged to attend school on a regular basis and receive support to maintain as normal a lifestyle as possible. Physical and occupational therapists should be included in the treatment team to prevent the development of stiffness in muscles and to maintain functional mobility. A prompt diagnosis should be sought and specific therapy instituted for all suspected infections. For patients who have normal levels of serum immunoglobulins and normal antibody responses to vaccines, immunization with influenzae and pneumococcal vaccines may be helpful. For patients with total IgG, or IgG subclass deficiencies, and/or patients who have problems making normal antibody responses to vaccines, therapy with gammaglobulin may be indicated.

Specific attention should be paid to swallowing function. Patients who aspirate or have food and liquids entering their trachea and lungs may improve when thin liquids are eliminated from their diet. In some individuals, a tube from the stomach to the outside of the abdomen (gastrostomy tube) may be necessary to eliminate the need for swallowing large volumes of liquids and to decrease the risk of aspiration.

Diagnostic X-rays should be limited because of the theoretical risk that the X-ray may cause a chromosomal break resulting in the development of a malignancy. In general, X-rays should only be done if the result will influence therapy and there is no other way to obtain the information that the X-ray will provide.

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Specific Therapy

Specific therapy for Ataxia-Telangiectasia (AT) is not possible at the present time. The use of thymic transplants, thymic hormones, and bone marrow transplantation has not led to improvement. Similarly, there is no evidence that any specific supplemental nutritional therapy is beneficial. However, now that the gene has been identified and the gene's normal function is being studied, it is hoped that new and specific therapy will soon become available.

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Expectations

In general, Ataxia-Telangiectasia (AT) follows a progressive course. However, it must be stressed that the course of the disease can be quite variable and it is difficult to predict the course in any given individual. Even within families, where the specific genetic defect should be the same, some children have predominantly neurologic difficulties while others have recurrent infections and still others have neither neurologic difficulties nor recurrent infections for long periods of time. The course of the disease in most patients is characterized by progressive neurologic deterioration. Many patients are confined to a wheel chair in their teens. Infections of the lungs (bronchitis or pneumonia) and sinuses (sinusitis) are common and may damage the lungs even if treated promptly. Malignancies or cancers are also more common in patients with AT. They can be treated but may require modifications of standard chemotherapy protocols.

It should be emphasized, however, that although the above course is the most typical, the course of AT varies considerably from patient to patient. Some patients have been able to attend college and live independently, and some have lived into the fifth decade of life.

We would like to thank the Immune Deficiency Foundation, www.primaryimmune.org, for their contribution of the above information.

If you or your physician would like additional information on this disease please click here
or visit www.atsociety.org.uk.

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Disclaimer: The information contained on these pages is not intended to provide specific medical advice; rather it is intended for informational purposes only, in order to provide a better understanding of these diseases. Please consult with a qualified physician for diagnosis and answers to your questions.

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