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IKBA GAIN-OF-FUNCTION MUTATION IN A FEMALE PRESENTING WITH INFECTIONS AND HYPER IgM, BUT WITHOUT ECTODERMAL DYSPLASIA.

Friday, March 24, 2017
Grand Ballroom II/III (The Westin Seattle)
Cristina Swanson, MD PhD (University of Washington and Seattle Children's Hospital)

RATIONALE: Autosomal dominant anhidrotic ectodermal dysplasia with immune deficiency (AD-EDA-ID) is caused by heterozygous IkBa mutations. Usual features include combined immune deficiency, recurrent infections, and ectodermal dysplasia. We report a female with recurrent infections, hyper IgM, and no ectodermal dysplasia who was found to have a heterozygous IkBa mutation.

METHODS: Immunophenotyping, functional flow cytometry, and gene sequencing were done.

RESULTS: The patient presented in infancy with E. coli bacteremia and numerous respiratory and gastrointestinal viral infections. She had no ectodermal dysplasia. Immune evaluation at 5 months found leukocytosis (43,000 cells/uL), elevated IgM (425 mg/dL) and normal IgG (237 mg/dL). Immunophenotyping showed expanded naïve T cells with normal proliferation to PHA, but no response to CD3 stimulation. Vaccine responses were poor. Sequencing identified a previously characterized heterozygous IkBa mutation (p.S32I), which causes a phosphorylation defect that prevents ubiquitin mediated degradation. She has been treated with IgG replacement and antimicrobial prophylaxis, but not BMT.

CONCLUSIONS: Hyper IgM and variable ectodermal dysplasia are well described in NEMO deficiency but not in AD-EDA-ID. This case expands the spectrum of findings reported in AD-EDA-ID to include hyper-IgM and lack of ectodermal dysplasia.