ACase of GATA2 Deficiency with Pancytopenia and Recurrent Infections: To Transplant or Not to Transplant?

Abstract

BackgroundGATA2 deficiency is an autosomal dominant disorder arising from various mutations in the GATA2 gene, which encodes a zinc finger transcription factor that is required for hematopoiesis and angiogenesis. Patients with GATA2 deficiency can present with a range of hematologic and immunologic manifestations. We present a case of GATA2 deficiency with recurrent transient pancytopenia who is also heterozygous for C9 deficiency. Case presentationOur 30-year-old female patient presented with febrile neutropenia (ANC 850) and rash. Interestingly, she reported a history of recurrent viral upper respiratory infections since childhood and had mononucleosis at the age of 5. In her mid-twenties, she started having recurrent sinusitis and pneumonias, requiring hospitalization and antibiotic therapy 1–2 times per year. She also had persistent pancytopenia for at least 5 years that transiently improved with transfusions. CBC ranged from Hgb 5.5–10.1 g/dL (mean 8), platelets 30–102 K/uL (mean 67), WBC 1.4–5.6 K/uL (mean 2.87), neutrophils 0.75–4.35 K/uL (mean 2), monocytes 0–0.07 K/uL (mean 0.02), lymphocytes 0.38–1.18 K/uL (mean 0.8). Bone marrow biopsy showed severely hypocellular bone marrow with trilineage hypoplasia without dysplasia or neoplasia. We initiated an immune workup that showed normal IgG, IgA and IgM levels; low B cell numbers; absent NK cells (CD56+); and preserved T cell numbers on flow cytometry. Strep pneumoniae IgG levels were nonprotective with less than 0.1 ug/mL for all serotypes. Genetic panel testing for primary immunodeficiency revealed a heterozygous pathogenic mutation in GATA2 (c.1081C>T (p.Arg361Cys). Upon multidisciplinary discussion with Hematology, decision was made to begin immunoglobulin replacement. Bone marrow transplant workup was initiated, but the team is hesitant to proceed with transplant at this time. DiscussionHematopoietic stem cell transplantation is the only treatment option with curative potential for this patient, but there are significant associated morbidity and mortality risks. Identifying the appropriate timing for transplantation remains a central focus of this patient's care. Close monitoring of the patient's overall clinical evolution including peripheral cell counts, bone marrow findings, and infection frequency and severity could help approximate the optimal transplantation timing after careful consideration of risks and benefits.