Hereditary ataxia

Definition

Ataxia-telangiectasia (A-T), also called Louis-Bar syndrome, is a rare genetic disease. It affects multiple systems. Individuals with A-T usually die by their early 20s. Nervous system abnormalities become apparent by age 2, and muscle control progressively diminishes. Immune system deficiencies and blood cancers are common, and affected individuals are extremely sensitive to radiation.

Description

A-T first appeared in the medical literature in the mid-1920s, but wasn't named as a specific disorder until 1957. The name is a combination of two recognized disorders: ataxia (lack of muscle control) and telangiectasia (tiny, red spots). However, A-T is more than the sum of these two disorders. Other A-T- associated indicators include immune system deficiencies, extreme sensitivity to radiation, and blood cancers.

Medical researchers initially suspected that multiple genes (the units responsible for inherited features) were involved. However, in 1995, mutations in a single large gene were identified as causing A-T. The gene was named ATM (for A-T, mutated) and subsequent research revealed it has a significant role in regulating cell division. Normally, a proofreading and repair mechanism fixes DNA damage before cell replication continues. A-T cells seem to bypass this mechanism and continue growing and dividing.

A-T is very rare, affecting about 500 people in the United States. However, an estimated 0.5-1.4% of the population--approximately 2.5 million people--carry one copy of the mutated gene. Carriers may possibly experience ill effects, such as increased radiation sensitivity and higher cancer rates.

Causes & symptoms

The ATM gene is autosomal recessive, meaning the disease occurs only if a defective gene is inherited from both parents. Infants with A-T initially appear healthy. At around age 2, ataxia becomes apparent. The root cause of A-T-associated ataxia is cell death in the brain, specifically the large branching cells of the nervous system (Purkinje's cells) which are located in the middle layer of the lower part of the brain (the cerebellum). A toddler becomes clumsy and loses balance easily. Speech becomes slurred and more difficult, and the symptoms progressively worsen. Between ages 2-8, telangiectases, or tiny, red "spider" veins, appear on the cheeks and ears and in the eyes.

By age 10-12, children with A-T can no longer control their muscles. Immune system deficiencies vary between individuals but include lower-than-normal levels of proteins that function as antibodies (immunoglobulins) and white blood cells (blood cells not containing "iron" proteins). The thymus gland, which aids in development of the body's immune system, is either missing or has developed abnormally. Intelligence is normal, but growth may be retarded owing to immune system or hormonal deficiencies. Individuals with A-T are also sometimes afflicted with diabetes, prematurely graying hair, and difficulty swallowing.

As the children grow older, the immune system becomes weaker and less capable of fighting infection. In the later stages, recurrent respiratory infections and blood cancers, such as leukemia or lymphoma, are common.

Diagnosis

Diagnosis relies on recognizing the hallmarks of A-T: progressive ataxia and telangiectasia. However, this may be difficult as ataxia symptoms may appear prior to telangiectasia symptoms by several years. Other symptoms can vary between individuals; for example, 70% of individuals with A-T have a high incidence of respiratory infection, 30% do not. The identification of the ATM gene raises hopes that screening, and perhaps treatment, may be possible.

Treatment

There is currently no cure for A-T, and treatment revolves around managing the individual's symptoms. Physical therapy and speech therapy can help in adjusting to the ataxia. Injections of gamma globulin, or extracts of human blood that contain antibodies, are used to strengthen the weakened immune system and high-dose vitamin administrations may also be prescribed.

Prognosis

A-T is a fatal condition. Children with A-T become physically disabled by their early teens and typically die by their early 20s. In very rare cases, individuals with A-T may experience slower progression and a slightly longer life span, surviving into their 30s. A-T carriers have a five-fold higher risk than non-carriers of developing certain cancers, especially breast cancer. Patients with A-T are also prone to develop blood cancers and malignancies.

Prevention

Medical researchers are investigating methods for screening individuals who may be carriers of the defective gene. Prenatal testing for A-T is possible but not done routinely, because commercial screening tests have yet to be developed.

Key Terms

Ataxia

The inability to control voluntary muscle movement, most frequently resulting from disorders in the brain or spinal cord.

Autosomal

Relating to any of the chromosomes except for X and Y, the sex chromosomes.

Cerebellum

It is the lower part of the brain.

Gamma-globulin

An extract of human blood that contains antibodies. (An antibody is a substance produced in the blood that is capable of destroying toxins such as bacteria.)

Immunoglobulin

Proteins in the blood that are the component parts of antibodies. (An antibody is a substance produced in the blood that is capable of destroying foreign substances such as bacteria.)

Leukemia

A blood cancer in which white blood cells (leukocytes) grow at an unusually rapid rate.

Lymphoma

A blood cancer in which lymphocytes, a variety of white blood cells, grow at an unusually rapid rate.

Mutation

An error in the genetic code.

Purkinje's cells

Large branching cells of the nervous system.

Recessive

Producing no effect.

Telangiectases

The area at which dilated blood vessels have created a spidery red lesion.

Telangiectasia

Dilation of terminal blood vessels leading to the formation of telangiectases.

Thymus

A gland located in the front of the neck that coordinates the development of the immune system.

Further Reading

For Your Information

Periodicals

• Lavin, Martin F., and Yosef Shiloh. "The Genetic Defect in Ataxia-Telangiectasia." Annual Review of Immunology 15 (1997): 177.
• Nowak, Rachel. "Discovery of AT Gene Sparks Biomedical Research Bonanza." Science 268 (1995): 1700.

  Organizations

• A-T Children's Project. 1 W. Camino Real, Suite 212, Boca Raton, FL 33432-5966. (561) 395-2621 or (800) 543-5728. http://www.med.jhu.edu/ataxia/.
• A-T Medical Research Foundation. 5241 Round Meadow Rd., Hidden Hills, CA 91302. (818) 704-8146.
• A-T Project. 3002 Enfield Rd., Austin, TX 78703. (512) 472-3417.
• National Ataxia Foundation. 2600 Fernbrook Ln., Suite 119, Minneapolis, MN 55447- 4752. (61) 553-0020. http://www.ataxia.org/.
• National Institute of Neurological Disorders and Stroke. http://www.ninds.nih.gov/whatnew/presswhn/1995/a-t-2htm
• National Organization for Rare Disorders. P.O. Box 8923, New Fairfield, CT 06812- 1783. (203) 746-6518 or (800) 999-6673.

Gale Encyclopedia of Medicine. Gale Research, 1999.