Ataxia telangiectasia/chromosome breakage disorders


Ataxia telangiectasia (A-T), also called Louis-Bar syndrome or cerebello-oculocutaneous telangiectasia, is a rare, inherited disease that attacks the neurological and immune systems of children. A-T is a recessive disorder, meaning that it affects children who carry two copies of a defective (mutated) A-T gene, one copy from each parent. A-T affects the brain and many parts of the body and causes a wide range of severe disabilities.


Ataxia means poor coordination, and the telangiectasia are tiny, red spider blood vessels which develop in A-T patients, especially on the whites of the eyes and on the surface of the ears. A-T is a progressive disease that affects the cerebellum (the body's motor control center) and, in about 70 percent of cases, weakens the immune system as well, leading to respiratory disorders. The weakening of the immune system ( immunodeficiency ) resulting from A-T has been traced to defects in both B-cells and T-cells, the specialized white blood cells (lymphocytes) that defend the body against infection, disease, and foreign substances. In A-T children, B-cell responses are very weak, and levels of immunoglobulins, the proteins that B-cells make to fight infection by specific recognition of invading organisms, may also be low. T-cells are few and weak, and the thymus gland is immature. This is why A-T is also considered an immunodeficiency disease. A-T first shows itself in early childhood, usually at the toddler stage. The characteristic symptoms are lack of balance, slurred speech, and perhaps a higher-than-normal number of infections. All children at this age take a little while to develop good walking skills, coherent speech, and an effective immune system, so it often takes a few years before A-T is correctly diagnosed. Other features of the disease may include mild diabetes, premature graying of the hair, difficulty swallowing, and delayed physical and sexual development. Children with A-T usually have normal or above normal intelligence , but some cases of mental retardation have been reported.


A-T is genetically transmitted by parents who are carriers of the gene responsible for A-T. The A-T mode of inheritance is autosomal recessive (AR) and requires two copies of the predisposing gene—one from each parent—for the child to have the disease. Parents do not exhibit symptoms, but they each carry a recessive gene that may cause A-T in their offspring. In AR families, there is one chance in four that each child born to the parents will have the disorder. Every healthy sibling of an A-T patient has a 66 percent chance of being a carrier, like the parents.


According to the National Cancer Institute, the incidence of A-T is between one out of 40,000 and one out of 100,000 persons worldwide, and for Caucasians it is about three per million, so the disorder is very rare. In the United States, there are about 500 children with A-T with both males and females equally affected. An estimated 1 percent (2.5 million) of the general population carries one of the defective A-T genes. Carriers of one copy of this gene do not develop A-T but have a significantly increased risk of cancer (over 38 percent of children with A-T develop cancer).

Causes and symptoms

A-T is a genetic disorder, meaning that it is caused by a defect in a gene that is present in a person at birth. All people have genes that contain a few mistakes or variations that do not result in a disorder. Disorders result when the gene variations are significant enough to affect the function a gene controls. Variations that cause disease are called mutations and A-T results from a defective gene, the ATM gene (for ataxia telangiectasia, mutated), first identified in 1995. The ATM gene is located on the long arm of chromosome 11 at position 11q22-23. It encodes for (controls) the production of a protein that plays a role in regulating cell division following DNA damage. The various symptoms seen in A-T reflect the main role of this protein, which is to induce several cellular responses to DNA damage. The protein made by the ATM gene is located in the nucleus of the cell and normally functions to control the rate at which the cell grows. The ATM protein does this by sending signals and modifying other proteins in the cell, which then changes the function of the proteins. The ATM protein also interacts with other special proteins when DNA is damaged as a result of exposure to some type of radiation. If the strands of DNA are broken, the ATM protein coordinates DNA repair by activating repair proteins, which helps to maintain the stability of cells. Mutations in ATM prevent cells from repairing DNA damage, which may lead to cancer. Mutations can also signal cells in the brain to die inappropriately, causing the movement and coordination problems associated with A-T.

A-T affects several different organs in the body. The most important symptoms are as follows:

  • Neurologic abnormalities resulting in poor coordination and an unsteady gait (ataxia). Shortly after learning to walk, children with A-T begin to stagger. They tend to sway when they stand or sit and wobble when they walk. Jerking and tremors are present in about 25 percent of patients. This symptom results from neurologic abnormalities affecting the cerebellum that controls balance. Writing is affected by seven or eight years of age.
  • Dilated blood vessels (telangiectasia). Telangiectasias usually occur on the white portion of the eye or on the ears, neck and extremities.
  • Variable immunodeficiency resulting in increased vulnerability to infections. This symptom is a major feature in some individuals. The infections most commonly involve the lungs and sinuses and are usually of bacterial or viral origin. About 10 percent of patients have severe immunodeficiency.
  • Predisposition to certain types of cancer. At least 10 percent of all A-T patients, including adults, develop cancer. Most of these are cancers of the lymphoid tissues (leukemias and lymphomas), but one fifth of the cancers occur in the stomach, brain, ovary, skin, liver, larynx, parotid gland, and breast.

Additional clinical symptoms include the following:

  • autosomal recessive inheritance of the ATM gene
  • involuntary, rapid, rhythmic movement of the eyeball (nystagmus)
  • impaired ability to coordinate certain types of eye movements (oculomotor apraxia)
  • squint of ocular muscles
  • speech defect (dysarthria)
  • slow, writhing motions (choreoathetosis)
  • lack of T-lymphocytes (thymic aplasia)
  • albinism of hair
  • decreased to absent deep tendon reflexes
  • multiple skin changes including eczema and "coffee-with-milk"x colored spots
  • incomplete development of tonsils, lymph nodes, and spleen (hypoplasia)
  • seizures (any type)
  • abnormal ovaries
  • small testes
  • high blood sugar levels (hyperglycemia)

When to call the doctor

A-T children appear normal as infants. The decreased coordination of movements (ataxia) associated with A-T first becomes apparent when a child begins to walk, typically between 12 and 18 months of age. Toddlers with A-T are usually wobbly walkers. In their preschool years, children with A-T begin to stumble and fall, and drooling is frequent. Parents should contact their pediatrician if they observe any A-T signs or symptoms in their child. Telangiectasias are another typical warning sign. They become apparent after the onset of the ataxia, often between two and eight years of age.


Establishing a diagnosis for ataxia telangiectasia is most difficult in very young children, primarily because the full-blown syndrome is not yet apparent. As of 2004, the A-T diagnosis is usually based on the characteristic clinical findings and supported by laboratory tests that point to a defect of DNA (genes and chromosomes) and to an inability to repair some types of damage to DNA. Laboratory tests are helpful but not as important as the individual patient's symptoms and signs, family history, and complete neurological evaluation including a magnetic resonance imaging (MRI) scan of the brain. The cerebellum atrophies early in the disease, being visibly smaller on MRI examination by seven or eight years of age. Diagnosis is more difficult before the disorder has fully developed, when the child is still uncertain on his/her feet. The most difficult time to diagnose A-T is during the period when neurologic symptoms start to appear (early childhood) and the typical telangiectasias have not yet appeared. During this period, a history of recurrent infections and typical immunologic findings can suggest the diagnosis. Four tests are used to help establish the A-T diagnosis:

  • Increased alpha-fetoprotein levels in blood. Alpha-fetoproteins are fetal proteins that are usually produced during fetal development but may persist at high blood levels after birth. The vast majority of A-T patients (more than 95 percent) have elevated levels of serum alpha-fetoprotein. This test is considered good but yields similar results for other conditions.
  • Decreased immunoglobulin levels (Iga, IgG, IgM). Approximately 30 percent of patients with A-T have immunodeficiency. The drawback of this test is that immunoglobulin levels are not always low for A-T, and they are also low in other conditions.
  • Sequence analysis. Sequence analysis of the ATM coding region is available on a clinical basis. Sequencing detects more than 95 percent of ATM sequence alterations but significant difficulties exist in distinguishing normal variations from A-T-causing mutations.
  • Increased chromosome breaks and rearrangements. Individuals with A-T have an increased frequency of spontaneous breaks in their chromosomes as well as an increased frequency of chromosomal rearrangements. These chromosomal abnormalities often occur close to genes that control the function of white blood cells, such as immunoglobulins and T-lymphocytes. The frequency of chromosomal breaks is increased when T-lymphocytes are exposed to x rays in the laboratory, and this sensitivity to ionizing irradiation forms the basis for a specialized A-T diagnostic test.

The ionizing irradiation sensitivity test is the most useful test for diagnosing A-T. However, it can only be carried out in specialized centers and takes much longer than the other tests.

Because of its variable symptoms, A-T is often misdiagnosed as a form of cerebral palsy or as slow development.


As of 2004, there is no cure for ataxia telangiectasia, thus specific therapy is not available, and treatment is largely supportive. Patients are encouraged to participate in as many activities as possible. Children are encouraged to attend school on a regular basis and receive support to maintain as normal a lifestyle as possible. The following are some types of interventions have been shown to help those with the disorder:

  • Exercise and physiotherapy. These programs help prevent the development of stiffness in muscles and help maintain functional mobility, showing A-T patients how to best use muscle control and stretch muscles and ligaments.
  • Antibiotics, immunoglobulins, vaccinations. For patients who have normal levels of immunoglobulins and normal antibody responses to vaccines, immunization with influenza and pneumococcal vaccines may be helpful. For patients with total IgG deficiencies or patients who have problems making normal antibody responses to vaccines, therapy with gammaglobulin may be indicated.
  • Speech therapy. Speech therapy can significantly improve diction, especially in the second decade of the disorder.
  • Orthopedic referral/assessment. Corrective procedures can be helpful for joint or postural problems, particularly in the lower limbs or spine.

Because cells from patients with A-T are 30 percent more sensitive to ionizing radiation than the cells of normal individuals, any required radiotherapy or chemotherapy should be reduced or monitored carefully; conventional doses are contraindicated and are potentially lethal.

Alternative treatment

No single alternative medicine or herbal remedy can help people with A-T. The use of thymic transplants and hormones has not led to improvement. Similarly, there is no scientific evidence as of 2004 that any specific supplemental nutritional therapy is beneficial.

Concerning drug therapy, most drugs which act on the nervous system can cause problems in A-T. Some people have found Benzhexol beneficial, but others have suffered reactions to it. Drug therapy for A-T remains in 2004 experimental and accordingly requires highly specialized A-T clinical teams.

Since the 1995 isolation of the ATM gene, scientists have worked very hard to understand how the ATM protein is activated or turned on following damage to a cell's DNA. This knowledge is in turn being used to develop A-T treatment approaches. The following are among the most promising:

  • Gene therapy: Scientists are starting to test the efficiency of gene therapy protocols in mice and are simultaneously developing a new gene therapy protocol for A-T which would allow for stable, long-term production of the ATM protein.
  • Neural stem cells: Researchers have demonstrated a significant therapeutic effect by using neural stem cells in mice that have a pattern of neurodegeneration similar to A-T.
  • Bone marrow transplantation: Significant progress has been made in the development of a successful bone marrow transplantation protocol in mice with A-T. Researchers are testing how effectively this protocol prevents immune abnormalities and immune-related cancers in these mice.


Albinism —An inherited condition that causes a lack of pigment. People with albinism typically have light skin, white or pale yellow hair, and light blue or gray eyes.

Allele —One of two or more alternate forms of a gene.

Ataxia —A condition marked by impaired muscular coordination, most frequently resulting from disorders in the brain or spinal cord.

Atrophy —The progressive wasting and loss of function of any part of the body.

B-cell (B lymphocyte) —A small white blood cell from bone marrow responsible for producing antibody and serving as a precursor for plasma cells.

Carrier —A person who possesses a gene for an abnormal trait without showing signs of the disorder. The person may pass the abnormal gene on to offspring. Also refers to a person who has a particular disease agent present within his/her body, and can pass this agent on to others, but who displays no symptoms of infection.

Central nervous system —Part of the nervous system consisting of the brain, cranial nerves, and spinal cord. The brain is the center of higher processes, such as thought and emotion and is responsible for the coordination and control of bodily activities and the interpretation of information from the senses. The cranial nerves and spinal cord link the brain to the peripheral nervous system, that is the nerves present in the rest of body.

Cerebellum —The part of the brain involved in the coordination of movement, walking, and balance.

Chromosome —A microscopic thread-like structure found within each cell of the human body and consisting of a complex of proteins and DNA. Humans have 46 chromosomes arranged into 23 pairs. Chromosomes contain the genetic information necessary to direct the development and functioning of all cells and systems in the body. They pass on hereditary traits from parents to child (like eye color) and determine whether the child will be male or female.

Diabetes —A disease characterized by an inability to process sugars in the diet, due to a decrease in or total absence of insulin production.

DNA —Deoxyribonucleic acid; the genetic material in cells that holds the inherited instructions for growth, development, and cellular functioning.

Fetal proteins —Proteins that are usually produced during fetal development but may persist at high blood levels in some conditions (such as A-T) after birth. The vast majority of A-T patients (more than 95%) have elevated levels of serum alpha-fetoprotein.

Gene —A building block of inheritance, which contains the instructions for the production of a particular protein, and is made up of a molecular sequence found on a section of DNA. Each gene is found on a precise location on a chromosome.

Immune response —A physiological response of the body controlled by the immune system that involves the production of antibodies to fight off specific foreign substances or agents (antigens).

Immune system —The system of specialized organs, lymph nodes, and blood cells throughout the body that work together to defend the body against foreign invaders (bacteria, viruses, fungi, etc.).

Immunodeficiency —A condition in which the body's immune response is damaged, weakened, or is not functioning properly.

Immunoglobulin G (IgG) —Immunoglobulin type gamma, the most common type found in the blood and tissue fluids.

Leukemia —A cancer of the blood-forming organs (bone marrow and lymph system) characterized by an abnormal increase in the number of white blood cells in the tissues. There are many types of leukemias and they are classified according to the type of white blood cell involved.

Lymphocyte —A type of white blood cell that participates in the immune response. The two main groups are the B cells that have antibody molecules on their surface and T cells that destroy antigens.

Lymphocytic leukemia —An acute form of childhood leukemia characterized by the development of abnormal cells in the bone marrow.

Lymphoma —A diverse group of cancers of the lymphatic system characterized by abnormal growth of lymphatic cells. Two general types are commonly recognized–Hodgkin's disease and non-Hodgkin's lymphoma.

Magnetic resonance imaging (MRI) —An imaging technique that uses a large circular magnet and radio waves to generate signals from atoms in the body. These signals are used to construct detailed images of internal body structures and organs, including the brain.

Motor skills —Controlled movements of muscle groups. Fine motor skills involve tasks that require dexterity of small muscles, such as buttoning a shirt. Tasks such as walking or throwing a ball involve the use of gross motor skills.

Neurodegenerative disease —A disease in which the nervous system progressively and irreversibly deteriorates.

Nystagmus —An involuntary, rhythmic movement of the eyes.

Progressive —Advancing, going forward, going from bad to worse, increasing in scope or severity.

Recessive disorder —Disorder that requires two copies of the predisposing gene one from each parent for the child to have the disease.

Stem cell —An undifferentiated cell that retains the ability to develop into any one of a variety of cell types.

T cell —A type of white blood cell that is produced in the bone marrow and matured in the thymus gland. It helps to regulate the immune system's response to infections or malignancy.

Telangiectasia —Abnormal dilation of capillary blood vessels leading to the formation of telangiectases or angiomas.

Thymic aplasia —A lack of T lymphocytes, due to failure of the thymus to develop, resulting in very reduced immunity.

  • High throughput drug screening: Testing methods are also being developed to help scientists screen large numbers of already-approved drugs as well as new compounds to see if they are useful for treating A-T.
  • Transplants of thymus tissue: The new approaches that medical researchers are testing also include transplants of thymus tissue to boost the immune system.

Clinical trials

Parents may consider enrolling their A-T diagnosed child in a NIH-approved clinical trial. The first-ever A-T clinical treatment study took place at Children's Hospital in Philadelphia, with a second trial that started in 2000. In 2004, the A-T Clinical Center at Johns Hopkins Hospital in Baltimore also started a clinical study. Children who participate in these clinical trials receive complete immunological and neurological evaluations as part of being enrolled in the study. Many patients also receive nutritional evaluations and consultations as well.

Nutritional concerns

Some A-T patients have impaired swallowing function. Patients who aspirate or have food and liquids reaching their lungs have been shown to improve when thin liquids are removed from their diet. In some individuals, a tube from the stomach to the outside of the abdomen (gastrostomy tube) may be required to eliminate the need for swallowing large volumes of liquids and to decrease the risk of aspiration. Vitamin E supplements are often recommended, although the vitamin has not been formally tested for efficacy in patients with A-T.


Generally, the prognosis for individuals with A-T is poor. Those with the disease are frequently wheelchair-bound by their teens and usually die in their teens or early 20s. However, the course of the disease can be quite variable, and it is difficult to predict the outcome for any given individual as A-T varies considerably from patient to patient. Even within families, in which the specific genetic defect should be the same, some children have mostly neurologic problems while others have recurrent infections, and still others have neither neurologic problems nor recurrent infections.

There was no cure for A-T as of 2004. The cloning and sequencing of the ATM gene has opened several avenues of research with the goal of developing better treatment, including gene therapy and the design of drugs for more effective treatments. Research is also leading to a greater understanding of AT, increased awareness, and more genetic counseling.


In the past, A-T carriers were identified because they were parents of a child diagnosed with A-T. But the cloning of the ATM gene responsible for A-T as of 2004 allows physicians or cancer genetics professionals to conduct genetic testing, analyzing patients' DNA to look for A-T mutations in the ATM gene. Thus, prenatal diagnosis can be carried out in most families. Genetic counseling is also of benefit to prospective parents with a family history of ataxia-telangiectasia. Parents of a child diagnosed with A-T may have a slight increased risk of cancer. They should have genetic counseling and more intensive screening for cancer.

Parental concerns

Any family touched by ataxia telangiectasia is forever affected. Old assumptions have to be discarded and new, often very difficult, realities need to be accepted, including the uncertainty of the A-T outcome. Significant adjustments, both physical and psychological, are required, many of them agonizingly difficult. A-T support groups have been organized by all major A-T organizations, such as the Ataxia Telangiectasia Children's Project, the National Ataxia Foundation (NAF), and the Ataxia Telangiectasia Medical Research Foundation. These organizations are dedicated to improving the lives of families affected by A-T. They also provide the latest news on A-T research, information on coping with A-T, and personal accounts of living with A-T.

See also Immunodeficiency ; Magnetic resonance imaging .



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Ataxia Telangiectasia (A-T) Children's Project. 668 South Military Trail, Deerfield Beach, FL 33442–3023. Web site:>.

Ataxia Telangiectasia (A-T) Medical Research Foundation. 5241 Round Meadow Road, Hidden Hills, CA 91302. Web site:

National Ataxia Foundation (NAF). 2600 Fernbrook Lane, Suite 119, Minneapolis, MN 55447–4752. (763) Web site:

National Institute of Child Health and Human Development (NICHD). 31 Center Drive, Rm. 2A32, MSC 2425, Bethesda, MD 20892–2425. Web site:

National Organization for Rare Disorders (NORD). PO Box 1968, 55 Kenosia Avenue, Danbury, CT 06813–1968. (203) 744–0100.


"What is ataxia?" National Ataxia Foundation . Available online at (accessed November 22, 2004).

"Questions and Answers: Ataxia Telangiectasia." National Cancer Institute . Available online at (accessed November 22, 2004).

Monique Laberge, Ph.D.

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