Ataxia Telangiectasia

Definition

Definition of Ataxia Telangiectasia
Ataxia telangiectasia (A-T) (also referred to as Louis–Bar syndrome) is a rare, neurodegenerative, inherited disease causing severe disability. Ataxia refers to poor coordination and telangiectasia to small dilated blood vessels, both of which are hallmarks of the disease.[1]
A-T affects many parts of the body:

1. It impairs certain areas of the brain including the cerebellum, causing difficulty with movement and coordination.
2. It weakens the immune system causing a predisposition to infection.
3. It prevents repair of broken DNA, increasing the risk of cancer.

Symptoms

Symptoms of Ataxia Telangiectasia
There is substantial variability in the severity of features of A-T between affected individuals, and at different ages. The following symptoms or problems are either common or important features of A-T:

1. Ataxia (difficulty with control of movement) that is apparent early but worsens in school to pre-teen years
2. Oculomotor apraxia (difficulty with coordination of head and eye movement when shifting gaze from one place to the next)
3. Involuntary movements
4. Telangiectasia (dilated blood vessels) over the white (sclera) of the eyes, making them appear bloodshot. These are not apparent in infancy and may first appear at age 5–8 years. Telangiectasia may also appear on sun-exposed areas of skin.
5. Problems with infections, especially of the ears, sinuses and lungs
6. Increased incidence of cancer (primarily, but not exclusively, lymphomas and leukemias)
7. Delayed onset or incomplete pubertal development, and very early menopause
8. Slowed rate of growth (weight and/or height)
9. Drooling particularly in young children when they are tired or concentrating on activities
10. Dysarthria (slurred, slow, or distorted speech sounds)
11. Diabetes in adolescence or later
12. Premature changes in hair and skin

Causes

Causes of Ataxia Telangiectasia
Ataxia-telangiectasia is inherited, which means it is passed down through families. It is an autosomal recessive trait. This means that both parents must provide a defective gene for the child to have symptoms of the disorder.

The disease results from defects in the ataxia telangiectasia mutated (ATM) gene. Defects in this gene can lead to abnormal cell death in various places of the body, including the part of the brain that helps coordinate movement.

Diagnosis

Diagnosis of Ataxia Telangiectasia
The diagnosis of A-T is usually suspected by the combination of neurologic clinical features (ataxia, abnormal control of eye movement, and postural instability) with telangiectasia and sometimes increased infections, and confirmed by specific laboratory abnormalities (elevated alpha-fetoprotein levels, increased chromosomal breakage or cell death of white blood cells after exposure to X-rays, absence of ATM protein in white blood cells, or mutations in each of the person’s ATM genes).

A variety of laboratory abnormalities occur in most people with A-T, allowing for a tentative diagnosis to be made in the presence of typical clinical features. Not all abnormalities are seen in all patients. These abnormalities include:

1. Elevated and slowly increasing alpha-fetoprotein levels in serum after 2 years of age
2. Immunodeficiency with low levels of immunoglobulins (especially IgA, IgG subclasses, and IgE) and low number of lymphocytes in the blood
3. Chromosomal instability (broken pieces of chromosomes)
4. Increased sensitivity of cells to x-ray exposure (cells die or develop even more breaks and other damage to chromosomes)
5. Cerebellar atrophy on MRI scan

Treatment

Treatment of Ataxia Telangiectasia
There is no cure for A-T and, currently, no way to slow the progression of the disease. Treatment is symptomatic and supportive. Physical and occupational therapy help to maintain flexibility. Speech therapy is important, teaching children to control air flow to the vocal cords.  Gamma-globulin injections may be useful if immunoglobulin levels are sufficiently reduced to weaken the immune system. High-dose vitamin regimens and antioxidants such as alpha lipoic acid also may also be used.

Prognosis

Prognosis of Ataxia Telangiectasia
Average lifespan has been improving for years, for unknown reasons, and varies with the severity of the underlying mutations, ATM (ataxia-telangiectasia mutated) protein levels, and residual ATM kinase activity.  Some individuals with later onset of disease and slower progression survive into their 50s.

Prevention

Prevention of Ataxia Telangiectasia
Couples with a family history of this condition who are considering pregnancy may consider genetic counseling.

Parents of a child with this disorder may have a slight increased risk of cancer. They should have genetic counseling and more intensive cancer screenings.