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

Authors

Mika T¹, Vangala D¹, Eckhardt M¹, La Rosée P², Lange C^{3 4}, Lehmberg K⁵, Wohlschläger C⁶, Biskup S⁷, Fuchs I⁸, Mann J⁸, Ehl S⁸, Warnatz K^{9 10}, Schroers R¹

Department of Hematology and Oncology, Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany.
Klinik für Innere Medizin II, Schwarzwald-Baar-Klinikum, Villingen-Schwenningen, Germany.
Medical Clinic, Research Center Borstel, Borstel, Germany.
Respiratory Medicine & International Health, University of Lübeck, Lübeck, Germany.
Clinic for Pediatric Hematology, University Medical Center Eppendorf, Hamburg, Germany.
Hematopathology Lübeck, Lübeck, Germany.
CeGaT and Practice for Human Genetics, Tübingen, Germany.
Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg i.Br., Germany.
Department of Rheumatology and Clinical Immunology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg i.Br., Germany.
Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg i.Br., Germany.

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.

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