Makindo Medical Notes.com

Elevated alpha fetoprotein

About

• Very rare autosomal recessive condition Chromosome 11q
• A mutation of ATM (AT mutated) gene leads to a defect of DNA repair

Aetiology

• ATM codes phosphatidylinositol-3-kinase related genes
• This is involved in cell cycle control and mutation leads to a defect in DNA repair
• Increased sensitivity to ionizing radiation and Thymic hypoplasia

Pathophysiology

• There is Cerebellar degeneration and Posterior column loss
• Impaired cell-mediated and humoral Immune problems.
• Haematological malignancy
• Lung and sinus infections (especially pneumococcus)

Clinical

• It presents in children aged under 10 years old and
• Patient has apraxia for voluntary gaze - moves head rather than eyes is a very suggestive feature
• Choreiform movements, athetosis, myoclonic jerks
• Skin and conjunctival telangiectasia may be seen
• Sinus/Chest symptoms and infections
• Lymphadenopathy, fevers weight loss may suggest lymphoma
• Hypogonadism and Reduced lower limb reflexes

Complications

• B cell /T cell lymphoma and Hodgkin's and Non-Hodgkin's type
• Increased infections, Lung cancer, Breast cancer (in those with a single gene)

Investigations

• Increased alpha Fetoprotein and ↓ IgA ↓ IgE ↓ IgG2 ↓ IgG4
• MRI - Cerebellar atrophy with widened cerebellar Sulci and enlargement of the fourth ventricle which progresses with time and may not be obvious early on.

Management

• Prognosis is very poor with death within the early 2nd decade of life.
• Largely supportive
• Genetic counselling

Revisions

• Last updated 08/08/2017