Ataxia-telangiectasia Health Article

Definition

Ataxia-telangiectasia (A-T) is a rare, genetic neurological disorder that progressively affects various systems in the body. Children affected with A-T appear normal at birth; however, the first signs of the disease—usually a lack of balance and slurred speech—often appear between one and two years of age.

Description

The onset of cerebellar ataxia (unsteadiness and lack of coordination) marks the beginning of progressive degeneration of the cerebellum, the part of the brain responsible for motor control (movement). This degeneration gradually leads to a general lack of muscle control, and eventually confines the patient to a wheelchair. Children with A-T become unable to feed or dress themselves without assistance. Because of the worsening ataxia, children with A-T lose their ability to write, and speech also becomes slowed and slurred. Even reading eventually becomes impossible, as eye movements become difficult to control.

Children with A-T usually exhibit another symptom of the disease: telangiectases, or tiny red spider veins (dilated blood vessels). These telangiectases appear in the corners of the eyes—giving the eyes a blood-shot appearance—or on the surfaces of the ears and cheeks exposed to sunlight.

In about 70% of children with A-T, another symptom of the disease is present: an immune system deficiency that usually leads to recurrent respiratory infections. In many patients, these infections can become life threatening. Due to deficient levels of IgA and IgE immunoglobulins—the natural infection-fighting agents in the blood—children with A-T are highly susceptible to lung infections that are resistant to the standard antibiotic treatment. For these patients, the combination of a weakened immune system and progressive ataxia can ultimately lead to pneumonia as a cause of death.

Children with A-T tend to develop malignancies of the blood circulatory system almost 1,000 times more frequently than the general population. Lymphomas (malignant tumors of lymphoid tissues) and leukemias (abnormal overgrowth of white blood cells, causing tumor cells to grow) are particularly common types of cancer, although the risk of developing most types of cancer is high in those with A-T. Another characteristic of the disease is an increased sensitivity to ionizing radiation (high-energy radiation such as x rays), which means that patients with A-T frequently cannot tolerate the radiation treatments often given to cancer patients.

Demographics

Both males and females are equally affected by A-T. Epidemiologists estimate the frequency of A-T as between 1/40,000 and 1/100,000 live births. However, it is believed that many children with A-T, particularly those who die at a young age, are never properly diagnosed. Thus, the disease may occur much more often than reported.

It is also estimated that about 1% (2.5 million) of the American population carry a copy of the defective A-T gene. According to some researchers, these gene carriers may also have an increased sensitivity to ionizing radiation and have a significantly higher risk of developing cancer—particularly breast cancer in female carriers.

Causes and symptoms

Ataxia-telangiectasia is called a recessive genetic disorder because parents do not exhibit symptoms; however, each parent carries a recessive (unexpressed) gene that may cause A-T in offspring. The genetic path of A-T is therefore impossible to predict. The recessive gene may lie dormant for generations until two people with the defective gene have children. When two such A-T carriers have a child together, there is a 1-in-4 chance (25% risk) of having a child with A-T. Every healthy sibling of a child with A-T has a 2-in-3 chance (66% risk) of being a carrier, like his or her parents.

Although there is much variability in A-T symptoms among patients, the signs of A-T almost always include the appearance of ataxia between the ages of two and five. Other, less consistent symptoms may include neurological, cutaneous (skin), and a variety of other conditions.

Neurological

Neurological symptoms of A-T include:

• progressive cerebellar ataxia (although ataxia may appear static between the ages of two and five)
• cerebellar dysarthria (slurred speech)
• difficulty swallowing, causing choking and drooling
• progressive lack of control of eye movements
• muscle weakness and poor reflexes
• initially normal intelligence, sometimes with later regression to mildly retarded range

Cutaneous

Cutaneous symptoms include:

• progressive telangiectases of the eye and skin develop between two to ten years of age
• atopic dermatitis (itchy skin)
• Café au lait spots (pale brown areas of skin)
• cutaneous atrophy (wasting away)
• hypo- and hyperpigmentation (under pigmented and overpigmented areas of skin)
• loss of skin elasticity
• nummular eczema (coin-shaped inflammatory skin condition)

Other symptoms

Other manifestations of A-T include:

• susceptibility to neoplasms (tumors or growths)
• endocrine abnormalities
• tendency to develop insulin-resistant diabetes in adolescence
• recurrent sinopulmonary infection (involving the sinuses and the airways of the lungs)
• characteristic loss of facial muscle tone
• absence or dysplasia (abnormal development of tissue) of thymus gland
• jerky, involuntary movements
• slowed growth
• prematurely graying hair