Ataxia-Telangiectasia, Associated with a Rare 1339C>T ATM mutation, presenting in infancy with Pneumocystis carinii pneumonia, and an elevated serum IgM. (35.11)

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Abstract Ataxia-Telangiectasia (A-T) is an autosomal recessive disorder manifested by progressive immunodeficiency, progressive neurologic dysfunction, and an elevated cancer predisposition. Characteristic symptoms are rarely encountered during infancy. We present the laboratory and clinical studies of a patient with respiratory distress at age 3 months due to pneumocystis pneumonia. Laboratory studies demonstrated an elevated serum IgM (840 mg/dL), recurrent neutropenia, lymphopenia (CD3, CD4, CD8, and CD19), diminished in vitro lymphocyte proliferation, a negative HIV PCR, and normal ADA and PNP levels. Flow cytometry demonstrated normal lymphocyte expression of CD40 and the CD40 ligand. Sequencing, after PCR-amplification of genomic DNA, demonstrated no apparent mutation consistent with type 2 hyper IgM syndrome. Based on a significantly elevated serum alpha-fetoprotein and early neurologic deficits, a diagnosis of A-T was suspected. Subsequently, her cells were found to be radiosensitive, based on a Colony Survival Assay. Western blot analysis of nuclear lysates of patient cells failed to detect ATM protein. Molecular analysis of the ATM gene identified a rare homozygous 1339C>T mutation (previously reported in a Druze A-T family: Hum Mutat 11:69–75, 1998). Notably, our A-T case (AT219LA) demonstrates early and atypical findings of an opportunistic infection and elevated serum IgM. The patient is currently thriving on IVIG and the prophylactic use of Septra.