Frontiers in Immunology · Nov 11, 2026
Disseminated Mycobacterium avium Complex–Associated Hemophagocytic Lymphohistiocytosis Revealing GATA2 Deficiency and Clonal Hematopoiesis: A Case Report and Literature Review
By Luocheng Zhang, Yang Dai, Xushu Zhong et al.
Background: GATA2 deficiency is an inborn disorder of immunity and hematopoiesis associated with opportunistic infections, progressive cytopenias, clonal hematopoiesis, and myeloid neoplasms. Hemophagocytic lymphohistiocytosis (HLH) is an uncommon but increasingly recognized complication, often occurring in the setting of severe infection. We report a young adult in whom disseminated Mycobacterium avium complex (MAC) infection and secondary HLH led to the diagnosis of GATA2 deficiency, with subsequent identification of somatic STAG2 variants and a heterozygous germline PRF1 variant. Case Presentation: A 27-year-old man presented with recurrent fever, progressive lymphadenopathy, subcutaneous nodules, and cytopenias. Multisite microbiologic testing demonstrated disseminated MAC infection, and the clinical and laboratory findings fulfilled HLH-2004 criteria. Anti-mycobacterial therapy together with immunomodulatory treatment resulted in defervescence, regression of lymphadenopathy and skin lesions, and improvement in HLH-associated inflammatory markers; however, severe thrombocytopenia persisted. Further genetic evaluation identified a pathogenic germline GATA2 c.1192C>T (p.R398W) variant and a paternally inherited heterozygous PRF1 c.503G>A (p.S168N) variant, classified as pathogenic by the WES laboratory. Somatic profiling identified two STAG2 frameshift variants, c.1544_1547del (p.D515fs) and c.2036delC (p.P679fs), providing evidence of superimposed clonal hematopoiesis. Repeat bone marrow examination showed severe megakaryocytic hypoplasia despite active myeloid and erythroid proliferation. The patient subsequently developed recurrent severe infections, including Aspergillus fumigatus and Pneumocystis jirovecii, and developed shock with acute respiratory failure before allogeneic hematopoietic stem cell transplantation (allo-HSCT) could be performed. He was discharged in critical condition. Conclusion: This case highlights the overlapping immune and hematopoietic manifestations of GATA2 deficiency. Disseminated NTM infection in a young adult, particularly when accompanied by otherwise unexplained cytopenias, should prompt evaluation for an underlying inborn error of immunity. Importantly, improvement in infection-associated HLH does not necessarily indicate recovery of hematopoiesis; persistent or progressive cytopenia should prompt reassessment for intrinsic marrow dysfunction and acquired clonal abnormalities. The heterozygous PRF1 p.S168N variant may have represented an additional susceptibility factor, but its functional contribution to HLH could not be established. In patients with GATA2 deficiency, severe opportunistic infection together with persistent marrow dysfunction or clonal hematopoiesis should prompt early allo-HSCT assessment, with transplantation timing individualized according to infection control and overall clinical status.