Table 1.

The basic characteristics features, treatment, and outcome of the patients with GATA2 mutation and HLH

Study	Country	Age, Sex	PMH	Presentation	Genetic findings	HLH diagnosis	Infection	Treatment	Follow-up and outcome	Note
Wu et al., 2024	China	28, M	NA	Recurrent fever (Tmax 39.5 °C), night sweats, and afternoon/evening spikes temperature spikes for > 4 months prior to presentation; weight lost approximately 5 kg since onset.	Heterozygous missense variant in GATA2 gene (Gene location: chr3.128200691; Variant: c.1072G > A: p.A358T; Source: De novo).	Based on HLH-2004 diagnostic index (7/8).	M. avium, EBV.	HLH treatment: Ruxolitinib combined with doxorubicin-etoposide-methylprednisolone regimen; M. avium treatment: azithromycin, clofazimine, and amikacin.	1-year follow-up: Smaller lymph nodes, intermittent pulmonary infections, thrombocytopenia, enlarged spleen, negative for M. avium (NGS) and EBV-DNA.	The patient’s 3-year-old daughter had the same pathogenic GATA2 variant, but his parents and older brother did not; Patient unable to undergo allo-HSCT due to economic constraints.
		22, F	NA	Intermittent fever (Tmax 41 °C) without obvious cause, since 4 months prior to presentation.	Heterozygous missense variant in GATA2 gene (Gene location: chr3.128200155; Variant: c.1108 A > G: p.R370G; Source: De novo).	Based on HLH-2004 diagnostic index (5/8).	EBV	HLH treatment: Ruxolitinib combined with doxorubicin-etoposide-methylprednisolone regimen; patient proposed for allo-HSCT.	Condition stabilized, intermittently positive for EBV-DNA post-treatment, diagnosed with MDS three years later.	No GATA2 gene variant found in her parents;
		26, M	Fever, fatigue, and leukopenia for over 10 years; BM cytology suggests MDS not excluded.	Chest tightness and fever without obvious triggers, since 1 month prior to presentation.	Heterozygous missense variant in GATA2 gene (Gene location: chr3.128200118; Variant: c.1145G > A: p.R382Q; Source: Unverified).	Based on HLH-2004 diagnostic index (6/8).	M. kansasii, EBV.	Rifampicin, doxycycline, and gentamicin with a poor anti-infection effects.	Patient experienced sustained pancytopenia and repeated infections.	His father died of acute leukemia; Patient unable to undergo allo-HSCT due to economic constraints.
Huang et al., 2023	china	28, M	Intermittent fever (for 3 years) and erythema nodosa (for 7 months) that treated with various antibiotics, but fever persisted mostly in the afternoon and at night.	Recurrent fever; lymphadenopathy; pancytopenia; splenomegaly; erythema nodosa	Heterozygous nonsense variant in GATA2 gene (Variant: c.599dupG, p.Ser201*)	Based on HLH-2004 diagnostic index.	M. avium; Klebsiella pneumonia	Cyclosporin, dexamethasone, ruxolitinib, and 4-drug antituberculosis therapy.	Died from severe pulmonary infection one month later.	The GATA2 variant in this patient creates stop codons, leading to the absence of both zinc finger domains; his father and sister carried the wild type of the GATA2 gene. The absence of this variant in the proband’s father and sister suggesting it might be a de novo mutation.
Burak et al., 2021	USA	22, F	Congenital absence of the right kidney, right-sided hearing loss, and leukopenia (negative BM biopsy); history of infectious mononucleosis at age 13 years; frequent upper respiratory viral infections, vaginal candida infections, and severe acne.	Generalized malaise, fever, chest pain, cough, and shortness of breath for 3 weeks; At admission: headaches, weakness, fevers, chills, lack of appetite, palpitations, severe anxiety, sinus tachycardia, tachypnea, and fever (Tmax 39.4 °C), splenomegaly.	Heterozygous mutation in the GATA2 gene (Variant: c.1009 C > T, p.Arg337*)	Based on HLH-2004 diagnostic index (5/8).	CMV	Ganciclovir, intravenous Ig, dexamethasone 10 mg/m², followed by high dosage corticosteroids (IV methylprednisolone, 40 mg/d);	After 18 days in hospital, discharged for acute rehabilitation on a steroid taper and valganciclovir, 900 mg every 12 h. Finally, haploidentical human leukocyte antigen bone marrow transplant approximately 11 months after being diagnosed with GATA2 deficiency.	Her father had benign leukopenia, but no other pertinent family history; this patient exhibits loss of C-terminal zinc-finger domain.
Mika et al., 2021	Germany	29, F	None.	Recurrent fever (Tmax 40 °C) for more than 1 year, admitted after fever persisted for over two weeks.	Heterozygous nonsense variant in GATA2 gene (Variant: c.177 C > G, p.Tyr59Ter; Source: De novo)	Based on HLH-2004 diagnostic index (7/8); HScore of 239 points (98–99% probability of HLH).	M. avium.	Treatment with amikacin, azithromycin, ethambutol, rifampicin, high-dose dexamethasone, ciclosporin A, IVIG, and repetitive courses of etoposide (75 mg/m², twice weekly) was initiated promptly. Prior to allo-HSCT, the antimycobacterial treatment was switched to azithromycin, clofazimine, and ethambutol. Finally, allo-HSCT therapy following fludarabine (150 mg/m²) and treosulfan (30 g/m²); GVHD prophylaxis: post-transplant cyclophosphamide (100 mg/kg), mycophenolate-mofetil, and ciclosporin.	Complete remission of all inflammatory manifestations was achieved on day + 240 post-allo-HSCT, following 12 months of tuberculostatic therapy.	Family history and GATA2 genetic analysis of first-degree relatives revealed no additional affected individuals; this patient exhibits loss of both zinc finger domains in GATA2.
Sun et al., 2021	China	17, F	At age 6, recurrent fever was observed. At age 10, she had severe pneumonia, pleural effusion, and an erythematous and vesicular skin rash. Anti-VZV antibodies and DNA were detected in her peripheral blood. Three months later, she was diagnosed with HLH. Two years later, erythema nodosa on her lower limbs, accompanied by panniculitis.	Recurrent fever; pancytopenia; splenomegaly; erythema nodosa; panniculitis	Heterozygous nonsense mutation in the GATA2 gene (Variant: c.610 C > T, p.Arg204*)	Based on HLH-2004 diagnostic index	VZV at age 10.	Dexamethasone 10 mg/12 h and GCSF.	Death.	Her father had GATA2 mosaicism, while her 32-year-old sister carried the same mutation as the patient without manifestations; this patient exhibits loss of both zinc finger domains in GATA2;
Oleaga-Quintas et al., 2021	Spain	27?/M	NA	Inferior vena cava thrombosis; deafness	Mutation in the GATA2 gene (Variant: c.1035_1036insTC TGGCC/WT)	NA.	At the age of 24 years, M. kansasii infection of the lymph nodes, followed by a disseminated infection three years later; other: C. freundii (bacteremia), Staphylococcus spp., and Candida spp (esophagitis).	Long-term antibiotic therapy.	Death.	Patient didn’t undergo allo-HSCT.
Barber et al., 2021	USA	21, F	Multiple ear infections within the first few years of life; multiple episodes of pneumonia, bronchitis, and sinusitis; osteomyelitis of her finger occurred after a fracture at two years of age; probable PCD.	Intermittent lower respiratory tract infections.	Heterozygous mutation in the GATA2 gene (Variant: c.1009 C > T, p.Arg337*)	Based on BM biopsy.	EBV	NA.	Over the three-month hospitalization she developed progressive respiratory failure secondary to HLH and died.	Patient didn’t undergo allo-HSCT.
Suzuki et al., 2020	Japan	27, F	History of pancytopenia with refractory fever of unknown origin at ages 18 and 23; history of cervical dysplasia, and urticarial rash induced by physical stimulus since age 21;	Eight-day history of persistent fever and pancytopenia; at admission: fever (Tmax 40.2 °C), hepatosplenomegaly, and urticarial rash on her right forearm;	Heterozygous mutation in the GATA2 gene (Variant: c.1061 C > T, p. Thr354Met)	Based on HLH-2004 diagnostic index.	CMV; MRSA	HLH treatment: methylprednisolone pulse therapy (1000 mg for 5 days) was followed by maintenance therapy with prednisolone (1 mg/kg/day); MRSA treatment: CT-guided drainage for femoral abscess, vancomycin, daptomycin, teicoplanin, trimethoprim/sulfamethoxazole, doxycycline, minocycline.	NA	There was no similar family history;
Eguchi et al., 2018	Japan	14, M	Diagnosed with MDS at age 11.	Prolonged fever and weight loss.	Heterozygous frameshift mutation in the GATA2 gene (Variant: c.1077_1078insA)	Based on HLH-2004 diagnostic index.	M. kansasii	HLH treatment: etoposide, cyclosporine, and prednisolone; Antituberculosis therapy: isoniazid, rifampin, and ethambutol; Six months later, he underwent unrelated BM transplantation with conditioning using total body irradiation, etoposide, fludarabine, and melphalan.	He remains well with full donor chimerism 16 months post-transplant.	The patient’s healthy mother had the same mutation with reduced B cells but not monocytes.
Prader et al., 2018	Switzerland	8, F	In the preceding month, persistent warts and recurrent furuncles on the hands and feet.	Abdominal pain, erythematous vesicular skin rash, and subfebrile body temperatures over 4 days.	Heterozygous mutation in the GATA2 gene (Variant: c.1172_1175del, p.E391Gfs∗85)	Based on HLH-2004 diagnostic index (5/8)	VZV	VZV treatment: acyclovir, intravenous Ig (0.4 g/kg); HLH treatment: corticosteroids (1.5 mg/kg/d).	Relapsed after one year, recovered with corticosteroids and broadspectrum antibiotic	The patient’s spleen was not enlarged;
		7, M	Known case of GATA2 mutation for three years, manifesting as recurrent fever, oral aphthosis, recurrent furunculosis, and lymphopenia (affecting CD4 T cells, B cells, and NK cells).	Mild fever (Tmax 38.5 °C); erythematous vesicular skin rash; cough; splenomegaly.	Mutation in the GATA2 gene (Variant: c.(16 bp tandem repeat in exon 4), p.T347fs)	Based on HLH-2004 diagnostic index (4/6)	VZV	VZV treatment: acyclovir, VZIG (22 IU/kg), IVIG (0.4 g/kg); HLH treatment: corticosteroids (2 mg/kg/d).	NA.	The patient’s mother had treatment-resistant warts on her hands with an identical genotype (p.T347fs).
Parta et al., 2018	USA	17, F	Known case of GATA2 mutation for five years,	NA.	Karyotype: trisomy 8; mutation in the GATA2 gene (Variant: p.R396Q)	NA.	CMV; parvovirus	HSCT therapy from haploidentical related donor recipients with BM donor source.	The patient experienced grade 2 upper gastrointestinal acute GVHD despite post-transplantation cyclophosphamide treatment; After 12 months post-transplant, the patient is alive.	Negative family history.
Donadieu et al., 2018	France And Belgium	26, F	Known case of GATA2 mutation since age 19.	NA.	Karyotype: Trisomy 1q Der9 t(1;9)(q12;q1 2), r(9)(q12 ;q ?3 4), 11q23(2); nonsense mutation in the GATA2 gene (Variant: c.610 C > T, p.R204*)	NA.	CMV; EBV; M. avium; VZV; HPV (cutaneous warts);	GCSF; EPO; interferon; chemotherapy.	Death.	CMV infection caused HLH.
		57, ?	Known case of GATA2 mutation since age 21.	NA.	Karyotype: Del5 Del7 T8 Add 10 Del12 Monosomy 18, Monosomy 21; missense mutation in the GATA2 gene (Variant: c.937 C > T, p.H313Y)	NA.	EBV, HSV.	HSCT.	Death.	EBV-related hemophagocytic syndrome and lymphoproliferative disease occurred post-HSCT.
		24, F	Known case of GATA2 mutation since age 21.	NA.	Karyotype: 46,XX [20] / 92,XXXX [2]; missense mutation in the GATA2 gene (Variant: c.1061 C > G, p.T354R)	NA.	M. avium; pulmonary aspergillosis; mucormycosis; HPV (genital warts.	NA.	Death.	M. avium was the cause of HLH and death; the patient also experienced sarcoidosis;
		28, ?	Known case of GATA2 mutation since age 14.	NA.	Karyotype: normal; frameshift mutation in the GATA2 gene (Variant: c.1142del, p.Asn381Metfs*6)	NA.	Influenza A; aspergillosis; candidiasis; streptococcus sepsis; HPV (cutaneous warts);	NA.	Alive.	Influenza A virus infection caused HLH.
		10, ?	Known case of GATA2 mutation since age 9.	NA.	Karyotype: monosomy 7; missense mutation in the GATA2 gene (Variant: c.1186 C > T, p.R396W)	NA.	Aspergillosis post-HSCT.	HSCT	Death.	The patient also experienced atypical Kawasaki disease.
		40, ?	Known case of GATA2 mutation since age 19.	NA.	Karyotype: normal; missense mutation in the GATA2 gene (Variant: c.1193G > A, p.R398Q)	NA.	Mycobacteriosis.	HSCT	Alive.	The patient developed splenic vein thrombosis and had a rectal adenoma (low-grade dysplasia).
Yamamoto et al., 2018	Japan	20, M	Treated EBV-associated HLH with prednisolone 2 years ago.	NA.	Karyotype: normal; mutation in the GATA2 gene (Variant: p.R230Hfs*44); acquired STAG2 mutation (splicing site change, c.820–2 A > G)	NA.	EBV	allo-HSCT from an unrelated donor;	Alive without relapse.	The patient’s father was diagnosed with MDS in his youth and died from leukoencephalopathy around the age of 50; acquired STAG2 mutation could contribute to MDS progression.
Cohen et al., 2016	USA	24, F	At age 10: vesicular eruption; at age 20: necrotizing lymphadentitis, urinary Histoplasmosis; at age 21: small and large intestine perforation, panniculitis, Weber-Christian disease, two cerebral ischemic infarcts, E. faecium bacteremia, disseminated M. avium infection, DVT, PE, vertebral compression fracture, multiple deep skin ulcers, and osteomyelitis	Fever, diffuse ulcerations in the small intestine and skin.	Unialleleic expression; heterozygous for genomic SNPs exon 2 bp 55 A > C and exon 3 c.15 C > G, hemizygous by cDNA sequence	Based on HLH-2004 diagnostic index (6/8)	EBV	Dexamethasone; etoposide; alemtuzumab; allo-HSCT.	HSCT complicated by liver GVHD, no lymphoma detected, low EBV DNA in blood (low thousands/ml), virus mainly in B cells.	She was finally treated with haploidentical HSCT from her unaffected sister.
Spinner et al., 2016	USA	18, F	At age 9: severe bilateral lower extremity lymphedema; at age 12: necrotizing pneumonia with pulmonary abscess, lung biopsy identified thick-walled budding yeasts identified as Blastomyces dermatitidis on culture.	Fever; headache	frameshift mutation in the GATA2 gene (Variant: c.871 + 2_3insT)	NA.	HSV-1; Blastomyces dermatitidis	Dexamethasone; vancomycin; meropenem; levofloxacin; acyclovir; liposomal amphotericin B	Death.	None.

PMH, past medical history; HLH, hemophagocytic lymphohistiocytosis; M, male; NA, not applicable/available; Tmax, maximum temperature; M. avium, mycobacterium avium; EBV, epstein-barr virus; NGS, next-generation sequencing; allo-HSCT, allogeneic hematopoietic stem cell transplantation; F, female; MDS, myelodysplastic syndrome; BM, bone marrow; M. kansasii, mycobacterium kansasii; USA, united states of america; CMV, cytomegalovirus; IV, intravenous; IVIG, intravenous immunoglobulin; GVHD, graft-versus-host disease; VZV, varicella-zoster virus; GCSF, granulocyte colony-stimulating factor; C. freundii, citrobacter freundii; PCD, primary ciliary dyskinesia; MRSA, methicillin-resistant staphylococcus aureus; VZIG, varicella zoster immune globulin; IU/kg, international unit per kilogram; HPV, human papillomavirus; EPO, erythropoietin; HSV, herpes simplex virus; E. faecium, enterococcus faecium; DVT, deep vein thrombosis; PE, pulmonary embolism