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A 3-year-old with progressive cerebellar ataxia is noted to have oculocutaneous telangiectasias. He has had recurrent sinopulmonary infections. Labs show elevated AFP, low IgA, and lymphopenia. A chest CT is avoided due to radiation sensitivity.
AR; ATM (ataxia-telangiectasia mutated, a serine/threonine kinase involved in DNA double-strand break repair)
- ATM heterozygous carriers: increased breast cancer risk (~2x; ATM is a moderate-penetrance breast cancer gene)
Neurological:
- Progressive cerebellar ataxia (onset age 1-4 years, wheelchair-bound by adolescence)
- Oculomotor apraxia
- Dysarthria, choreoathetosis
Telangiectasias:
- Conjunctival and cutaneous (appear age 3-6 years)
Immunodeficiency:
- Variable T and B cell deficiency
- Low IgA, IgG subclass deficiency
- Recurrent sinopulmonary infections
Cancer predisposition:
- Lymphoma and leukemia (especially in childhood)
- Increased risk of solid tumors in adulthood
- Radiation sensitivity: avoid unnecessary X-rays and CT scans
Lab findings:
- Elevated serum AFP (~95%)
- Elevated chromosomal breakage (diagnostic test)
- Elevated serum AFP (present in ~95%) plus low or absent IgA and IgG subclasses supports the diagnosis in a child with ataxia and telangiectasias
- Radiosensitivity assays and increased chromosomal breakage (including translocations involving chromosomes 7 and 14) on irradiated lymphocytes
- Absent or reduced ATM protein on immunoblot; ATM sequence and deletion/duplication analysis confirms the diagnosis and enables carrier and prenatal testing
- Avoid ionizing radiation (X-rays, CT scans)
- Immunoglobulin replacement for severe immunodeficiency
- Aggressive treatment of pulmonary infections
- Cancer surveillance
- Physical and occupational therapy for ataxia
- No curative treatment; median survival ~25 years
The name of the disease is very helpful here:
- Patients present with ataxia (loss of balance) and telangiectasias (vessels on different surfaces of the body)
- The gene involved is ATM = Ataxia Telangiectasia, Mutated.