Abstract
<title>Abstract</title> <p> <bold>Background</bold> The co-occurrence of pure red cell aplasia (PRCA), congenital malformations, and severe opportunistic infections in children suggests an underlying systemic genetic disorder. We report a case of a child with PRCA, polydactyly, and fatal Pneumocystis jirovecii pneumonia (PJP) to illustrate an emergency phenotype-driven diagnostic approach. <bold>Case Presentation</bold> A school-aged girl, born with left thumb polydactyly and a cup-shaped ear, had a family history of early childhood mortality. Since April 2022, she experienced recurrent severe normocytic anemia and pulmonary infections. In January 2025, bone marrow studies confirmed PRCA, and initial chest CT revealed bilateral pneumonia. After cyclosporine and prednisone treatment, hemoglobin normalized. From September to November 2025, she was readmitted with fever, dyspnea, and oral thrush. Chest CT showed rapidly progressive diffuse ground-glass opacities with interlobular septal thickening. Bronchoalveolar lavage metagenomic next-generation sequencing detected Pneumocystis jirovecii (2,337 reads), cytomegalovirus, and Candida albicans, confirming PJP with co-infections. Despite discontinuing immunosuppressants and initiating anti-infective therapy plus intravenous immunoglobulin, her condition deteriorated. Severe hypogammaglobulinemia (IgG 537.32 mg/dL, IgA 46.10 mg/dL, IgM 30.73 mg/dL) and persistent monocytopenia were documented. The terminal chest CT demonstrated a crazy-paving pattern, with the radiology report noting that "pulmonary alveolar proteinosis should be considered." The family declined aggressive treatment, and the child died shortly after discharge. <bold>Conclusions</bold> The constellation of congenital polydactyly, PRCA, persistent monocytopenia, severe hypogammaglobulinemia, fatal PJP, and crazy-paving pattern on chest CT strongly suggests a genetic bone marrow failure/immunodeficiency syndrome such as GATA2 deficiency. Phenotype-driven early recognition and urgent intervention are crucial even without genetic confirmation. </p>