B63-07 Rare Autosomal-dominant Agammaglobulinemia Identified in a Female Infant Evaluated for Recurrent Pneumonia

Background 
Agammaglobulinemia is an X-linked disorder related to BTK mutations. Autosomal inheritance is markedly less common. We present a case of autosomal dominant (AD) agammaglobulinemia in an infant due to a heterozygous SPI1 variant. Case Report 
A full term 21-month-old female with negative neonatal course and newborn screen (including severe combined immunodeficiency) presented to clinic with recurrent pneumonia after the first year of life and persistent purulent nasal drainage since birth. She developed four pneumonias prior to presentation with radiographic clearance between infections. Family history is negative for immunodeficiency. On presentation she had stable vital signs: respiratory rate: 26bpm, heart rate:148bpm temperature:98.6F, SpO2 97% in room air. Physical exam revealed nasal congestion, bilateral rhonchi and oral thrush. Laboratory evaluation revealed agranulocytosis (ANC 0), agammaglobulinemia (IgG <75 mg/dL, IgA <10 mg/dL, and IgM <20 mg/dL), WBC :4, platelets :377, hemoglobin: 10.9. Patient admitted for evaluation of immunodeficiency. Lymphocyte subsets showed absent B cells and no serologic response to Haemophilus influenzae and pneumococcal vaccines. She received antimicrobials for chlamydophilia pneumonia (positive respiratory PCR) and IVIG. IgG level improved and ANC normalized. Bronchoalveolar lavage was negative for fungal, bacterial and viral organisms. Bone marrow biopsy showed paucity of B cells and a left shift granulopoiesis. Chest computed tomography showed mosaic attenuation and small airway involvement which may indicate post-infectious bronchiolitis obliterans, follicular bronchitis, or granulomatous lymphocytic interstitial lung disease. Duodenal biopsy showed absence of plasma cells, chronic gastritis and candidal esophagitis. Whole-genome sequencing identified a heterozygous SPI1 variant, a gene encoding the PU.1 protein that is involved with binding sites in the BTK promoter region associated with disruptions in B cell development2. Findings consistent with autosomal-dominant PU.1-mutated agammaglobulinemia. She was discharged after resolution of pneumonia. Rheumatology will continue long-term IVIG therapy. She is continued on inhaled steroids and follow up CT chest scheduled. Discussion This is a unique case of AD agammaglobulinemia. The co-occurrence of absolute neutropenia and B-cell agenesis contributed to the diagnostic uncertainty, particularly in a female without a family history of inherited immunodeficiency This case adds to the limited clinical descriptions of SPI1-associated agammaglobulinemia and illustrates how atypical cytopenias at presentation may initially divert consideration away from an underlying primary immunodeficiency. Conclusion This case reports a unique mode of inheritance for SPI1-associated agammaglobulinemia and emphasizes the importance of maintaining a high index of suspicion for primary immunodeficiency in children with recurrent pneumonias in an atypical presentation. This abstract is funded by: None