Case Report: Hemophagocytic Lymphohistiocytosis and Non-Tuberculous Mycobacteriosis Caused by a Novel GATA2 Variant

Front Immunol. 2021 May 10:12:682934. doi: 10.3389/fimmu.2021.682934. eCollection 2021.

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a disorder of uncontrolled immune activation with distinct clinical features including fever, cytopenia, splenomegaly, and sepsis-like symptoms. In a young adolescent patient a novel germline GATA2 variant (NM_032638.5 (GATA2): c.177C>G, p.Tyr59Ter) was discovered and had resulted in non-tuberculous mycobacterial (NTM) infection and aggressive HLH. Strikingly, impaired degranulation of cytotoxic T-lymphocytes (CTL) and natural killer (NK)-cells was detected in CD107a-analyses. The affected patient was treated with HLA-matched unrelated alloHSCT, and subsequently all hematologic and infectious abnormalities including HLH and NTM resolved. This case supports early alloHSCT in GATA2 deficiencies as curative approach regardless of active NTM infection. Future studies on GATA2 c.177C>G, p.Tyr59*Ter might unravel its potential role in cytotoxic effector cell function and its contribution to HLH pathogenesis.

Keywords: CD107a; GATA2; allogeneic hematopoietic stem cell transplantation; hemophagocytic lymphohistiocytosis; non-tuberculous mycobacteriosis.

Publication types

  • Case Reports

MeSH terms

  • Biomarkers
  • Disease Management
  • Female
  • GATA2 Transcription Factor / genetics*
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Genetic Variation*
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Immunophenotyping
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Lymphohistiocytosis, Hemophagocytic / diagnosis*
  • Lymphohistiocytosis, Hemophagocytic / genetics*
  • Lymphohistiocytosis, Hemophagocytic / therapy
  • Male
  • Mycobacterium Infections, Nontuberculous / diagnosis*
  • Mycobacterium Infections, Nontuberculous / genetics*
  • Mycobacterium Infections, Nontuberculous / therapy
  • Positron Emission Tomography Computed Tomography
  • Treatment Outcome

Substances

  • Biomarkers
  • GATA2 Transcription Factor
  • GATA2 protein, human