1. What is ataxia telangiectasia?

   Ataxia telangiectasia (A-T) is a primary immunodeficiency disease which affects a number of different organs in the body. An immunodeficiency disease is one that causes the immune system to break down, making the body susceptible to diseases. It is a rare, recessive genetic disorder of childhood that occurs in between 1 out of 40,000 and 1 out of 100,000 persons worldwide. The ailment is progressive. Patients with A-T are frequently wheelchair-bound by their teens, and the disease is generally fatal to patients by the time they reach their twenties.

   A-T is characterized by neurological problems, particularly abnormalities of balance, recurrent sinus and respiratory infections, and dilated blood vessels in the eyes and on the surface of the skin. Patients usually have immune system abnormalities and are very sensitive to the effects of radiation treatments.

   In the United States, where recurrent infections typical of the disorder are usually controlled by antibiotics, patients are at high risk of developing and dying of cancer, particularly leukemias and lymphomas.

2. What are the signs of ataxia telangiectasia?

   The first signs of the disease, which include delayed development of motor skills, poor balance, and slurred speech, usually occur during the first decade of life. Telangiectasias (tiny, red "spider" veins), which appear in the corners of the eyes or on the surface of the ears and cheeks, are characteristic of the disease, but are not always present and generally do not appear in the first years of life. About 20% of those with A-T develop cancer, most frequently acute lymphocytic leukemia or lymphoma. Many individuals with A-T have a weakened immune system, making them susceptible to recurrent respiratory infections. Other features of the disease may include mild diabetes mellitus, premature graying of the hair, difficulty swallowing, and delayed physical and sexual development. Children with A-T usually have normal or above normal intelligence.

3. Is the disorder curable?

   There is no cure for A-T at this time. The cloning and sequencing of the gene (named ATM, for ataxia telangiectasia, mutated) has opened several avenues of research to develop better treatment, including: (1) gene therapy; (2) the design of drugs to correct the function of the altered protein; and (3) direct replacement of the functional protein. Physical, occupational and speech therapy are used to help maintain flexibility, gamma-globulin injections help supplement the immune systems of A-T patients and high-dose vitamin regimens are being researched with some moderate results.

   Research shows that a protein kinase called ATM reacts to DNA damage by chemically modifying and triggering accumulation of a molecular or tumor suppressor called p53. This tumor suppressor is defective in about half of all human cancers and is the master control switch for a process that normally prevents cells from dividing. In A-T patients, the ATM protein is missing or defective. This delays the accumulation of p53, allowing cells to replicate without repair of their DNA and thereby increasing the risk of cancer. This research was reported by two separate groups of researchers in the September 1998 issue of Science.

4. What does it mean that the disorder is recessive?

   A recessive disorder requires two copies of the predisposing gene—one from each parent—for the child to have the disease.

5. What is a carrier?

   A carrier is a person with one normal and one altered copy of a gene that is linked to a particular disease. These individuals usually do not realize they are carriers because the disease is not present or its signs and symptoms are very mild.

   A person with one normal copy and one altered copy of the ATM gene is an A-T carrier.

6. How many A-T carriers are there in the United States?

   An estimated one percent of the U.S. population, or about 2.5 million people, may be carriers of A-T. A-T has no racial, economic, geographic or education barriers. Both males and females are equally affected. It is believed that many children with A-T, particularly those who die at a young age, are never properly diagnosed. Therefore, this disease may actually be much more common than projected.

7. How do I know if I'm a carrier?

   In the past, carriers were identified mainly because they were parents of a child with A-T. With the cloning of the ATM gene, however, physicians or cancer genetics professionals can now conduct genetic testing, analyzing patients' DNA to look for A-T mutations in the ATM gene. The genetic testing is complex and difficult, however; definitive results may not be possible. One of the most helpful laboratory tests used to assist in the diagnosis of A-T is the measurement of "fetal proteins," or serum alpha-fetoprotein, in the blood. These are proteins that are usually produced during fetal development but may persist at high 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. 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 A-T a virtual certainty.

8. Do A-T patients have an increased risk of developing cancer? If so, what cancers?

   Yes. Overall, the risk of an A-T patient developing any cancer is 37-fold higher than individuals in the general population. The risk of developing lymphoid tumors, however, the most frequently diagnosed cancers in A-T patients, is 100-fold higher than in the general population; A-T patients have about a 10 percent risk of developing lymphoma or leukemia. Cancers also occur in the stomach, brain, ovary, skin, liver, larynx, parotid gland, and breast.

9. Do A-T carriers have an increased risk of developing cancer? If so, what cancers?

   Definitive information does not yet exist to answer this question, but some scientists believe that A-T carriers, compared with the general population, might have a higher risk of certain cancers. In population-based studies, the most consistent elevations are for breast cancer, and possibly stomach cancer. These elevations, when seen, are small.

   Animal models have not supported the theory of increased cancer risk in A-T carriers. In animal studies of ATM, virtually all mice with the disease died of cancer, while no A-T carrier mice have yet to show tumors.

   Case-control studies have suggested a link between the ATM gene and increased breast cancer risk, but findings have been inconsistent. The National Cancer Institute (NCI) is currently funding two large, international studies to further examine the risk of cancer in A-T families.

10. Are A-T patients sensitive to radiation?

    Yes. A-T patients have an increased sensitivity to ionizing radiation, the type found in X-rays. When cultured in the laboratory, the blood and skin cells of these patients have markedly reduced ability to replicate and to form cell colonies after X-ray exposure.

11. Are A-T carriers sensitive to the effects of radiation?

    This is a question that needs further research. When cultured in the laboratory, blood and skin cells of known ATM gene carriers are less sensitive to X-rays than cells from A-T patients, and more sensitive than cells from the general public. There are not yet data from clinical studies to definitively answer the question about sensitivity of carriers. The NCI is currently funding a large, multi-institutional study to better understand the interaction between radiation exposure and the ATM gene.

12. Are X-rays harmful to A-T patients?

    A-T patients are sensitive to the effects of radiation and should be monitored for adverse effects. However, they do receive diagnostic X-rays when necessary.

    The information about radiation sensitivity in A-T comes largely from observations of A-T patients who undergo radiation treatments, especially for cancer, and also from laboratory studies on skin and blood cells. Physicians who treat A-T patients limit X-ray exposures by using the most modern equipment and techniques available, but they do recommend these diagnostic tests when needed.

13. Is it dangerous for carriers to have diagnostic X-rays, given their possible increased sensitivity to radiation compared to the general public?

    At this point, the evidence overall does not show a documented risk to A-T carriers. However, diagnostic X-rays should be limited because of the theoretical risk that the X-ray may cause a chromosomal break, which could result 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.

14. Suppose I learn I am an A-T carrier. Will mammography increase my chances of getting breast cancer?

    There is not yet definitive evidence that A-T carriers of any age have increased sensitivity to X-rays from mammograms or other diagnostic tests.

    Clinical breast examination and breast ultrasound are approaches to screening that avoid radiation exposure. When exposure to radiation is required, doctors who treat A-T carriers should use the most modern equipment and technology available, in order to minimize radiation exposure.

15. What about environmental sources of radiation, such as cellular phones? Should A-T carriers avoid these exposures?

    In NCI studies to date, no link has been found between non-ionizing radiation—such as that from cellular phones and power lines—and cancer.

16. What studies does NCI have under way to answer these questions more definitively?

    NCI is sponsoring a wide variety of research on A-T, DNA mutations and repair, and the interaction between ATM and mutations in BRCA1 and 2 (breast cancer susceptibility genes). Clinical scientists at NCI have over 30 years of experience with A-T, and are continuing research to develop better diagnostic tests, immune dysfunction analyses, and treatments.

    In addition, NCI is supporting three large, multi-national studies investigating A-T. One population-based study, a collaboration of investigators from the United States, Canada, Costa Rica, Germany, Israel, Italy, Poland, and Turkey, is examining the risk of cancer in A-T patients and their relatives. NCI is conducting another analysis of cancer risk in A-T families in collaboration with registries in Norway, Sweden, Denmark, and Finland. Another large, multi-site study, taking place in the United States and Denmark, is investigating whether women who are ATM carriers who have received radiation therapy as part of breast cancer treatment are at high risk of developing a second breast cancer in the other breast (second primary contralateral breast cancer).

# # #

Related NCI materials and Web pages:

• National Cancer Institute Fact Sheet 5.28, Screening Mammograms: Questions and Answers ¹
  (http://www.cancer.gov/cancertopics/factsheet/Detection/screening-mammograms)
• Hodgkin Lymphoma Home Page ²
  (http://www.cancer.gov/cancertopics/types/hodgkin)
• Non-Hodgkin Lymphoma Home Page ³
  (http://www.cancer.gov/cancertopics/types/non-hodgkin)
• Leukemia Home Page ⁴
  (http://www.cancer.gov/cancertopics/types/leukemia)

NCI's Cancer Information Service

Telephone (toll-free): 1–800–4–CANCER (1–800–422–6237)
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Glossary Terms

Not normal. An abnormal lesion or growth may be cancer, premalignant (likely to become cancer), or benign (not cancer).

An aggressive (fast-growing) type of leukemia (blood cancer) in which too many lymphoblasts (immature white blood cells) are found in the blood and bone marrow. Also called acute lymphoblastic leukemia and ALL.

An unexpected medical problem that happens during treatment with a drug or other therapy. Adverse effects do not have to be caused by the drug or therapy, and they may be mild, moderate, or severe. Also called adverse event.

A protein normally produced by a fetus. AFP levels are usually undetectable in the blood of healthy adult men or women (who are not pregnant). An elevated level of AFP suggests the presence of either a primary liver cancer or germ cell tumor. Also called AFP.

A change resulting in something that is different from the original.

A process in which anything complex is separated into simple or less complex parts.

An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models.

A drug used to treat infections caused by bacteria and other microorganisms.

A rare, inherited, progressive, degenerative disease of childhood that causes loss of muscle control, a weakened immune system, and an increased risk of cancer.

A tissue with red blood cells, white blood cells, platelets, and other substances suspended in fluid called plasma. Blood takes oxygen and nutrients to the tissues, and carries away wastes.

A tube through which the blood circulates in the body. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins.

A gene on chromosome 17 that normally helps to suppress cell growth. A person who inherits certain mutations (changes) in a BRCA1 gene has a higher risk of getting breast, ovarian, prostate, and other types of cancer.

A gene on chromosome 13 that normally helps to suppress cell growth. A person who inherits certain mutations (changes) in a BRCA2 gene has a higher risk of getting breast, ovarian, prostate, and other types of cancer.

Glandular organ located on the chest. The breast is made up of connective tissue, fat, and breast tissue that contains the glands that can make milk. Also called mammary gland.

A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is a cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord. Also called malignancy.

Having to do with the examination and treatment of patients.

A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called clinical trial.

Having to do with the opposite side of the body.

To heal or restore health; a treatment to restore health.

A disease in which the body does not control the amount of glucose (a type of sugar) in the blood and the kidneys make a large amount of urine. This disease occurs when the body does not make enough insulin or does not use it the way it should.

The process of identifying a disease, such as cancer, from its signs and symptoms.

A specific test or series of steps done to help diagnose a disease or condition. Mammograms and colonscopies are examples of diagnostic procedures.

To widen or enlarge an opening or hollow structure beyond its usual size, such as the pupil of the eye or a blood vessel.

In medicine, a disturbance of normal functioning of the mind or body. Disorders may be caused by genetic factors, disease, or trauma.

The molecules inside cells that carry genetic information and pass it from one generation to the next. Also called deoxyribonucleic acid.

Any substance, other than food, that is used to prevent, diagnose, treat or relieve symptoms of a disease or abnormal condition. Also refers to a substance that alters mood or body function, or that can be habit-forming or addictive, especially a narcotic.

A state of not functioning normally.

The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein.

Treatment that alters a gene. In studies of gene therapy for cancer, researchers are trying to improve the body's natural ability to fight the disease or to make the cancer cells more sensitive to other kinds of therapy.

Inherited; having to do with information that is passed from parents to offspring through genes in sperm and egg cells.

Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder.

The complex group of organs and cells that defends the body against infections and other diseases.

The decreased ability of the body to fight infections and other diseases.

Invasion and multiplication of germs in the body. Infections can occur in any part of the body and can spread throughout the body. The germs may be bacteria, viruses, yeast, or fungi. They can cause a fever and other problems, depending on where the infection occurs. When the body’s natural defense system is strong, it can often fight the germs and prevent infection. Some cancer treatments can weaken the natural defense system.

Use of a syringe and needle to push fluids or drugs into the body; often called a "shot."

A type of radiation made (or given off ) by x-ray procedures, radioactive substances, rays that enter the Earth's atmosphere from outer space, and other sources. At high doses, ionizing radiation increases chemical activity inside cells and can lead to health risks, including cancer.

A medical procedure that involves testing a sample of blood, urine, or other substance from the body. Tests can help determine a diagnosis, plan treatment, check to see if treatment is working, or monitor the disease over time.

The area of the throat containing the vocal cords and used for breathing, swallowing, and talking. Also called voice box.

Cancer that starts in blood-forming tissue such as the bone marrow and causes large numbers of blood cells to be produced and enter the bloodstream.

A large organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile.

Cancer that begins in cells of the immune system. There are two basic categories of lymphomas. One kind is Hodgkin lymphoma, which is marked by the presence of a type of cell called the Reed-Sternberg cell. The other category is non-Hodgkin lymphomas, which includes a large, diverse group of cancers of immune system cells. Non-Hodgkin lymphomas can be further divided into cancers that have an indolent (slow-growing) course and those that have an aggressive (fast-growing) course. These subtypes behave and respond to treatment differently. Both Hodgkin and non-Hodgkin lymphomas can occur in children and adults, and prognosis and treatment depend on the stage and the type of cancer.

A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Malignant cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of malignancy. Carcinoma is a malignancy that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a malignancy that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is a malignancy that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are malignancies that begin in the cells of the immune system. Central nervous system cancers are malignancies that begin in the tissues of the brain and spinal cord. Also called cancer.

The use of film or a computer to create a picture of the breast.

In medicine, having to do with the movement of body parts.

To change the genetic material of a cell. The changes (mutations) can be harmful, beneficial, or have no effect.

A part of the body that performs a specific function. For example, the heart is an organ.

One of a pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus.

A tumor suppressor gene that normally inhibits the growth of tumors. This gene is altered in many types of cancer.

Medical doctor.

A molecule made up of amino acids that are needed for the body to function properly. Proteins are the basis of body structures such as skin and hair and of substances such as enzymes, cytokines, and antibodies.

The use of high-energy radiation from x-rays, gamma rays, neutrons, protons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body near cancer cells (internal radiation therapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that travels in the blood to tissues throughout the body. Also called irradiation and radiotherapy.

A treatment plan that specifies the dosage, the schedule, and the duration of treatment.

To make a copy or duplicate of something.

Checking for disease when there are no symptoms. Since screening may find diseases at an early stage, there may be a better chance of curing the disease. Examples of cancer screening tests are the mammogram (breast), colonoscopy (colon), Pap smear (cervix), and PSA blood level and digital rectal exam (prostate). Screening can also include checking for a person’s risk of developing an inherited disease by doing a genetic test.

The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed.

An organ that is part of the digestive system. The stomach helps digest food by mixing it with digestive juices and churning it into a thin liquid.

An indication that a person has a condition or disease. Some examples of symptoms are headache, fever, fatigue, nausea, vomiting, and pain.

A type of gene that makes a protein called a tumor suppressor protein that helps control cell growth. Mutations (changes in DNA) in tumor suppressor genes may lead to cancer. Also called antioncogene.

A procedure in which high-energy sound waves are bounced off internal tissues or organs and make echoes. The echo patterns are shown on the screen of an ultrasound machine, forming a picture of body tissues called a sonogram. Also called ultrasonography.

A nutrient that the body needs in small amounts to function and stay healthy. Sources of vitamins are plant and animal food products and dietary supplements. Some vitamins are made in the human body from food products. Vitamins are either fat-soluble (can dissolve in fats and oils) or water-soluble (can dissolve in water). Excess fat-soluble vitamins are stored in the body’s fatty tissue, but excess water-soluble vitamins are removed in the urine. Examples are vitamin A, vitamin C, and vitamin E.

A type of high-energy radiation. In low doses, x-rays are used to diagnose diseases by making pictures of the inside of the body. In high doses, x-rays are used to treat cancer.