title: Diffuse parenchymal lung disease as first clinical manifestation of GATA-2 deficiency in childhood.
abstract: BACKGROUND
  GATA-2 transcription factor deficiency has recently been described in patients with a propensity towards myeloid malignancy associated with other highly variable phenotypic features: chronic leukocytopenias (dendritic cell-, monocyto-, granulocyto-, lymphocytopenia), increased susceptibility to infections, lymphatic vasculature abnormalities, and sensorineural deafness. Patients often suffer from opportunistic respiratory infections; chronic pulmonary changes have been found in advanced disease.
  
  
  METHODS
  We present a case of a 17-year-old previously healthy Caucasian male who was admitted to the hospital with fever, malaise, headache, cough and dyspnea. A chest X-ray revealed bilateral interstitial infiltrates and pneumonia was diagnosed. Despite prompt clinical improvement under antibiotic therapy, interstitial changes remained stable. A high resolution computer tomography showed severe diffuse parenchymal lung disease, while the patient's pulmonary function tests were normal and he was asymptomatic. Lung tissue biopsy revealed chronic reparative and resorptive reaction with organizing vasculitis. At the time of the initial presentation to the hospital, serological signs of acute infection with Epstein-Barr virus (EBV) were present; EBV viremia with atypical serological response persisted during two-year follow up. No other infectious agents were found. Marked monocytopenia combined with B-cell lymphopenia led to a suspicion of GATA-2 deficiency. Diagnosis was confirmed by detection of the previously published heterozygous mutation in GATA2 (c.1081 C > T, p.R361C). The patient's brother and father were both carriers of the same genetic defect. The brother had no clinically relevant ailments despite leukocyte changes similar to the index patient. The father suffered from spondylarthritis, and apart from B-cell lymphopenia, no other changes within the leukocyte pool were seen.
  
  
  CONCLUSIONS
  We conclude that a diagnosis of GATA-2 deficiency should be considered in all patients with diffuse parenchymal lung disease presenting together with leukocytopenia, namely monocyto-, dendritic cell- and B-lymphopenia, irrespective of severity of the clinical phenotype. Genetic counseling and screening for GATA2 mutations within the patient's family should be provided as the phenotype is highly variable and carriers without apparent immunodeficiency are still in danger of developing myeloid malignancy. A prompt recognition of this rare condition helps to direct clinical treatment strategies and follow-up procedures.
authors: Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic. tamara.svobodova@lfmotol.cuni.cz.
authors: Tamara
authors: T
authors: Svobodova
authors: Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic. ester.mejstrikova@lfmotol.cuni.cz.
authors: Ester
authors: E
authors: Mejstrikova
authors: Center for Chronic Immunodeficiency (CCI), University Medical Center and University of Freiburg, Freiburg im Breisgau, Germany. ulrich.salzer@uniklinik-freiburg.de.
authors: Ulrich
authors: U
authors: Salzer
authors: Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic. martina.sukova@fnmotol.cz.
authors: Martina
authors: M
authors: Sukova
authors: Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic. petr.hubacek@lfmotol.cuni.cz.|Department of Medical Microbiology, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic. petr.hubacek@lfmotol.cuni.cz.
authors: Petr
authors: P
authors: Hubacek
authors: Department of Pathology and Molecular Medicine, Thomayer's University Hospital, Prague, Czech Republic. radoslav.matej@ftn.cz.
authors: Radoslav
authors: R
authors: Matej
authors: Department of Respiratory Medicine, Thomayer's University Hospital, Prague, Czech Republic. martina.vasakova@ftn.cz.
authors: Martina
authors: M
authors: Vasakova
authors: Department of Pathology and Molecular Medicine, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic. hornofova@centrum.cz.
authors: Ludmila
authors: L
authors: Hornofova
authors: Department of Radiology, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic. marcela.dvorakova@fnmotol.cz.
authors: Marcela
authors: M
authors: Dvorakova
authors: Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic. eva.fronkova@lfmotol.cuni.cz.
authors: Eva
authors: E
authors: Fronkova
authors: Department of Pediatrics, 3rd Faculty of Medicine, Charles University in Prague and University Hospital Kralovske Vinohrady, Prague, Czech Republic. felix.votava@fnkv.cz.
authors: Felix
authors: F
authors: Votava
authors: Molecular Genetics Lab, Centre for Cardiovascular Surgery and Transplantation, Brno, Czech Republic. tomas.freiberger@cktch.cz.|Department of Clinical Immunology and Allergology, Medical Faculty, Masaryk University Brno, Brno, Czech Republic. tomas.freiberger@cktch.cz.
authors: Tomas
authors: T
authors: Freiberger
authors: Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic. petr.pohunek@lfmotol.cuni.cz.
authors: Petr
authors: P
authors: Pohunek
authors: Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic. jan.stary@lfmotol.cuni.cz.
authors: Jan
authors: J
authors: Stary
authors: Center for Chronic Immunodeficiency (CCI), University Medical Center and University of Freiburg, Freiburg im Breisgau, Germany. ales.janda@uniklinik-freiburg.de.|Department of Pediatric Infectious Diseases and Rheumatology, Center of Pediatrics and Adolescent Medicine, University Medical Center and University of Freiburg, Mathildenstrasse 1, 79106, Freiburg im Breisgau, Germany. ales.janda@uniklinik-freiburg.de.
authors: Ales
authors: A
authors: Janda
mesh_terms: D000293:Adolescent; D001402:B-Lymphocytes / Q000276:immunology; D020031:Epstein-Barr Virus Infections / Q000235:genetics* / Q000276:immunology; D050989:GATA2 Transcription Factor / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007970:Leukopenia / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000000981:diagnostic imaging / Q000473:pathology*; D017563:Lung Diseases, Interstitial / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D008231:Lymphopenia / Q000235:genetics* / Q000276:immunology; D008297:Male; D009000:Monocytes / Q000276:immunology; D009154:Mutation; D011859:Radiography; D013577:Syndrome; D014657:Vasculitis / Q000175:diagnosis / Q000235:genetics / Q000276:immunology
chemical_list: D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human