Makindo Medical Notes

Elevated alpha fetoprotein is a hallmark laboratory finding in Ataxia Telangiectasia.

About Ataxia Telangiectasia (A-T)

• Ataxia Telangiectasia is a very rare autosomal recessive disorder involving mutations on Chromosome 11q.
• Caused by a mutation in the ATM (Ataxia-Telangiectasia Mutated) gene, which results in defective DNA repair mechanisms.
• The ATM gene mutation affects cellular DNA repair processes, leading to increased vulnerability to DNA damage and cellular stress.

Aetiology

• The ATM gene codes for phosphatidylinositol-3-kinase related genes, which are essential for cell cycle control and DNA repair.
• This mutation leads to increased sensitivity to ionizing radiation and contributes to thymic hypoplasia, impairing immune function.

Pathophysiology

• Cerebellar degeneration: Leads to coordination and balance issues, with eventual posterior column loss.
• Impaired Immunity: Involves both cell-mediated and humoral immune deficiencies, predisposing patients to recurrent infections.
• Increased Malignancy Risk: High risk of hematologic malignancies, particularly lymphoma.
• Frequent Infections: Increased susceptibility to lung and sinus infections, especially by pneumococcus and other respiratory pathogens.

Clinical Presentation

• Typically presents in children under 10 years of age with progressive neurologic symptoms.
• Apraxia of gaze: Difficulty in voluntary eye movement; children often turn their head rather than moving their eyes, a highly suggestive feature.
• Neurological findings include choreiform movements, athetosis, and myoclonic jerks.
• Skin and Conjunctival Telangiectasia: Small, dilated blood vessels visible on the skin and eyes.
• Frequent Infections: Recurrent respiratory tract infections affecting the lungs and sinuses.
• Lymphadenopathy and Fevers: May indicate lymphoma development.
• Other Features: Hypogonadism and decreased reflexes in the lower limbs are commonly observed.

Complications

• Increased Malignancy Risk: High risk of B-cell and T-cell lymphomas, including both Hodgkin's and Non-Hodgkin’s lymphomas.
• Other Cancer Risks: Increased risk of lung and breast cancers, especially in carriers of a single ATM mutation.
• Recurrent Infections: Chronic lung infections and bronchiectasis due to immunodeficiency.

Investigations

• Alpha Fetoprotein (AFP): Elevated AFP is a typical laboratory finding in patients with A-T.
• Immunoglobulin Levels: Decreased IgA, IgE, IgG2, and IgG4, indicating immunodeficiency.
• MRI Imaging: Cerebellar atrophy with widened cerebellar sulci and enlargement of the fourth ventricle; these changes may become more pronounced over time.

Management

• Prognosis: Very poor, with life expectancy often limited to the early 20s due to complications.
• Supportive Care: Focuses on infection prevention, respiratory support, and symptomatic management.
• Genetic Counseling: Recommended for families due to the autosomal recessive inheritance pattern.