Síndrome de Whim como diagnóstico diferencial de neutropenia: relato de dois casos em um centro de referência pediátrico

Abstract

Introduction: WHIM syndrome is a rare, autosomal dominant disease classically characterized by warts, hypogammaglobulinemia, recurrent infections, and myelokathexis (leading to neutropenia). It is an inborn error of immunity caused by a variant in the CXCR4 gene, a receptor expressed in leukocytes, which prevents these cells from leaving the bone marrow into the bloodstream. Objective: To describe two clinical cases of WHIM syndrome to alert pediatricians to this disease as a differential diagnosis for patients with neutropenia. Methods: A retrospective, observational, descriptive case report study based on the medical record review of patients diagnosed with WHIM syndrome followed at the Immunology and Hematology outpatient clinics at IPPMG – UFRJ, along with a review of current literature via articles from PubMed, LILACS, and SciELO platforms over the last 10 years. Clinical Cases: Case 1: A 9-year-old girl with a history of severe recurrent infections and laboratory tests showing leukopenia and severe neutropenia, without hypogammaglobulinemia or warts. Hematoscopy revealed thin filaments between the nuclear lobes of the neutrophils, a finding described in WHIM patients. Case 2: A 4-year-old girl with laboratory tests showing leukopenia and chronic neutropenia, with no history of recurrent infections and an absence of hypogammaglobulinemia and warts. Bone marrow biopsy was suggestive of myelokathexis. In both cases, genetic sequencing was performed, revealing variants in the CXCR4 gene. Discussion: We highlight two cases of female pediatric patients with WHIM syndrome presenting with leukopenia and neutropenia, without hypogammaglobulinemia or warts—only one of whom had recurrent infections. It is important to emphasize that in patients with leukopenia (not just neutropenia) and signs of bone marrow hypercellularity, this diagnosis should be considered even in the absence of warts and hypogammaglobulinemia. Conclusion: Although rare, WHIM syndrome must be remembered as a differential diagnosis for patients with neutropenia.