TY - JOUR
T1 - GATA2 deficiency in children and adults with severe pulmonary alveolar proteinosis and hematologic disorders
AU - Griese, Matthias
AU - Zarbock, Ralf
AU - Costabel, Ulrich
AU - Hildebrandt, Jenna
AU - Theegarten, Dirk
AU - Albert, Michael
AU - Thiel, Antonia
AU - Schams, Andrea
AU - Lange, Joanna
AU - Krenke, Katazyrna
AU - Wesselak, Traudl
AU - Schön, Carola
AU - Kappler, Matthias
AU - Blum, Helmut
AU - Krebs, Stefan
AU - Jung, Andreas
AU - Kröner, Carolin
AU - Klein, Christoph
AU - Campo, Ilaria
AU - Luisetti, Maurizio
AU - Bonella, Francesco
PY - 2015/8/12
Y1 - 2015/8/12
N2 - Background: The majority of cases with severe pulmonary alveolar proteinosis (PAP) are caused by auto-antibodies against GM-CSF. A multitude of genetic and exogenous causes are responsible for few other cases. Goal of this study was to determine the prevalence of GATA2 deficiency in children and adults with PAP and hematologic disorders. Methods: Of 21 patients with GM-CSF-autoantibody negative PAP, 13 had no other organ involvement and 8 had some form of hematologic disorder. The latter were sequenced for GATA2. Results: Age at start of PAP ranged from 0.3 to 64 years, 4 patients were children. In half of the subjects GATA2-sequence variations were found, two of which were considered disease causing. Those two patients had the typical phenotype of GATA2 deficiency, one of whom additionally showed a previously undescribed feature - a cholesterol pneumonia. Hematologic disorders included chronic myeloic leukemia, juvenile myelo-monocytic leukemia, lymphoblastic leukemia, sideroblastic anemia and two cases of myelodysplastic syndrome (MDS). A 4 year old child with MDS and DiGeorge Syndrome Type 2 was rescued with repetitive whole lung lavages and her PAP was cured with heterologous stem cell transplant. Conclusions: In children and adults with severe GM-CSF negative PAP a close cooperation between pneumologists and hemato-oncologists is needed to diagnose the underlying diseases, some of which are caused by mutations of transcription factor GATA2. Treatment with whole lung lavages as well as stem cell transplant may be successful.
AB - Background: The majority of cases with severe pulmonary alveolar proteinosis (PAP) are caused by auto-antibodies against GM-CSF. A multitude of genetic and exogenous causes are responsible for few other cases. Goal of this study was to determine the prevalence of GATA2 deficiency in children and adults with PAP and hematologic disorders. Methods: Of 21 patients with GM-CSF-autoantibody negative PAP, 13 had no other organ involvement and 8 had some form of hematologic disorder. The latter were sequenced for GATA2. Results: Age at start of PAP ranged from 0.3 to 64 years, 4 patients were children. In half of the subjects GATA2-sequence variations were found, two of which were considered disease causing. Those two patients had the typical phenotype of GATA2 deficiency, one of whom additionally showed a previously undescribed feature - a cholesterol pneumonia. Hematologic disorders included chronic myeloic leukemia, juvenile myelo-monocytic leukemia, lymphoblastic leukemia, sideroblastic anemia and two cases of myelodysplastic syndrome (MDS). A 4 year old child with MDS and DiGeorge Syndrome Type 2 was rescued with repetitive whole lung lavages and her PAP was cured with heterologous stem cell transplant. Conclusions: In children and adults with severe GM-CSF negative PAP a close cooperation between pneumologists and hemato-oncologists is needed to diagnose the underlying diseases, some of which are caused by mutations of transcription factor GATA2. Treatment with whole lung lavages as well as stem cell transplant may be successful.
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U2 - 10.1186/s12890-015-0083-2
DO - 10.1186/s12890-015-0083-2
M3 - Article
AN - SCOPUS:84938899728
VL - 15
JO - BMC Pulmonary Medicine
JF - BMC Pulmonary Medicine
SN - 1471-2466
IS - 1
M1 - 87
ER -