title: Lung disease caused byABCA3mutations.
abstract: Knowledge about the clinical spectrum of lung disease caused by variations in the ATP binding cassette subfamily A member 3 (ABCA3) gene is limited. Here we describe genotype-phenotype correlations in a European cohort.
  
  
  
  We retrospectively analysed baseline and outcome characteristics of 40 patients with two disease-causing ABCA3 mutations collected between 2001 and 2015.
  
  
  
  Of 22 homozygous (15 male) and 18 compound heterozygous patients (3 male), 37 presented with neonatal respiratory distress syndrome as term babies. At follow-up, two major phenotypes are documented: patients with (1) early lethal mutations subdivided into (1a) dying within the first 6 months or (1b) before the age of 5 years, and (2) patients with prolonged survival into childhood, adolescence or adulthood. Patients with null/null mutations predicting complete ABCA3 deficiency died within the 1st weeks to months of life, while those with null/other or other/other mutations had a more variable presentation and outcome. Treatment with exogenous surfactant, systemic steroids, hydroxychloroquine and whole lung lavages had apparent but many times transient effects in individual subjects.
  
  
  
  Overall long-term (>5 years) survival of subjects with two disease-causing ABCA3 mutations was <20%. Response to therapies needs to be ascertained in randomised controlled trials.
authors: Department of Pediatric Pneumology, Dr. von Hauner Children's Hospital, LMU Munich, Munich, Germany.
authors: Carolin
authors: C
authors: Kröner
authors: Department of Pediatric Pneumology, Dr. von Hauner Children's Hospital, LMU Munich, Munich, Germany.
authors: Thomas
authors: T
authors: Wittmann
authors: Department of Pathology, LMU Munich, Munich, Germany.
authors: Simone
authors: S
authors: Reu
authors: Department of Pediatric Radiology, Dr. von Hauner Children's Hospital, LMU Munich, Munich, Germany.
authors: Veronika
authors: V
authors: Teusch
authors: Department of Neonatology, Klinikum Großhadern, LMU Munich, Munich, Germany.
authors: Mathias
authors: M
authors: Klemme
authors: Department of Pediatric Pneumology, Dr. von Hauner Children's Hospital, LMU Munich, Munich, Germany.
authors: Daniela
authors: D
authors: Rauch
authors: Department of Pediatric Pneumology, Dr. von Hauner Children's Hospital, LMU Munich, Munich, Germany.
authors: Meike
authors: M
authors: Hengst
authors: Department of Pediatric Pneumology, Dr. von Hauner Children's Hospital, LMU Munich, Munich, Germany.
authors: Matthias
authors: M
authors: Kappler
authors: Department of Pediatric Pneumonology, Ankara University Children's Hospital, Ankara University, Ankara, Turkey.
authors: Nazan
authors: N
authors: Cobanoglu
authors: Gazi University Hospital, Ankara University, Ankara, Turkey.
authors: Tugba
authors: T
authors: Sismanlar
authors: Gazi University Hospital, Ankara University, Ankara, Turkey.
authors: Ayse T
authors: AT
authors: Aslan
authors: Pneumology Unit, IRCCS San Matteo Hospital Foundation and University of Pavia, Pavia, Italy.
authors: Ilaria
authors: I
authors: Campo
authors: Department of Pediatric Pneumology, University Hospital Leuven, University Leuven, Leuven, Belgium.
authors: Marijke
authors: M
authors: Proesmans
authors: Department of Neonatology, University Hospital, University Mannheim, Mannheim, Germany.
authors: Thomas
authors: T
authors: Schaible
authors: Emma Children's Hospital, Academic Medical Center, Amsterdam, Netherlands.
authors: Susanne
authors: S
authors: Terheggen-Lagro
authors: Department of Pediatric Pneumology, Children's Hospital, Lucerne, Switzerland.
authors: Nicolas
authors: N
authors: Regamey
authors: Department of Pediatrics and Adolescent Medicine, Division of Pediatric Pulmonology and Allergology, Medical University of Graz, Graz, Austria.
authors: Ernst
authors: E
authors: Eber
authors: Department of Pediatric Pneumology and Allergology, Neonatology and Intensive Care, Klinikum Oldenburg, Medical Campus of University Oldenburg, Oldenburg, Germany.
authors: Jürgen
authors: J
authors: Seidenberg
authors: Clinic of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.
authors: Nicolaus
authors: N
authors: Schwerk
authors: Institute for Clinical Chemistry and Laboratory Medicine, University of Regensburg, Regensburg, Germany.
authors: Charalampos
authors: C
authors: Aslanidis
authors: Hohentwielstr. 32, 78250 Tengen, Germany.
authors: Peter
authors: P
authors: Lohse
authors: Department of Pathology, Academic Teaching Hospital Bielefeld, Bielefeld, Germany.
authors: Frank
authors: F
authors: Brasch
authors: Department of Pediatric Pneumology, Dr. von Hauner Children's Hospital, LMU Munich, Munich, Germany.
authors: Ralf
authors: R
authors: Zarbock
authors: Department of Pediatric Pneumology, Dr. von Hauner Children's Hospital, LMU Munich, Munich, Germany.
authors: Matthias
authors: M
authors: Griese
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D001706:Biopsy; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D003952:Diagnostic Imaging; D005260:Female; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D017563:Lung Diseases, Interstitial / Q000235:genetics* / Q000401:mortality; D008297:Male; D008854:Microscopy, Electron; D009154:Mutation; D010641:Phenotype; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: C441524:ABCA3 protein, human; D018528:ATP-Binding Cassette Transporters
keywords: ABCA3; Paediatric interstitial lung disease; Surfactant protein