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Lung disease caused by ABCA3 mutations
  1. Carolin Kröner1,
  2. Thomas Wittmann1,
  3. Simone Reu2,
  4. Veronika Teusch3,
  5. Mathias Klemme4,
  6. Daniela Rauch1,
  7. Meike Hengst1,
  8. Matthias Kappler1,
  9. Nazan Cobanoglu5,
  10. Tugba Sismanlar6,
  11. Ayse T Aslan6,
  12. Ilaria Campo7,
  13. Marijke Proesmans8,
  14. Thomas Schaible9,
  15. Susanne Terheggen-Lagro10,
  16. Nicolas Regamey11,
  17. Ernst Eber12,
  18. Jürgen Seidenberg13,
  19. Nicolaus Schwerk14,
  20. Charalampos Aslanidis15,
  21. Peter Lohse16,
  22. Frank Brasch17,
  23. Ralf Zarbock1,
  24. Matthias Griese1
  1. 1Department of Pediatric Pneumology, Dr. von Hauner Children's Hospital, LMU Munich, Munich, Germany
  2. 2Department of Pathology, LMU Munich, Munich, Germany
  3. 3Department of Pediatric Radiology, Dr. von Hauner Children's Hospital, LMU Munich, Munich, Germany
  4. 4Department of Neonatology, Klinikum Großhadern, LMU Munich, Munich, Germany
  5. 5Department of Pediatric Pneumonology, Ankara University Children's Hospital, Ankara University, Ankara, Turkey
  6. 6Gazi University Hospital, Ankara University, Ankara, Turkey
  7. 7Pneumology Unit, IRCCS San Matteo Hospital Foundation and University of Pavia, Pavia, Italy
  8. 8Department of Pediatric Pneumology, University Hospital Leuven, University Leuven, Leuven, Belgium
  9. 9Department of Neonatology, University Hospital, University Mannheim, Mannheim, Germany
  10. 10Emma Children's Hospital, Academic Medical Center, Amsterdam, Netherlands
  11. 11Department of Pediatric Pneumology, Children's Hospital, Lucerne, Switzerland
  12. 12Department of Pediatrics and Adolescent Medicine, Division of Pediatric Pulmonology and Allergology, Medical University of Graz, Graz, Austria
  13. 13Department of Pediatric Pneumology and Allergology, Neonatology and Intensive Care, Klinikum Oldenburg, Medical Campus of University Oldenburg, Oldenburg, Germany
  14. 14Clinic of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany
  15. 15Institute for Clinical Chemistry and Laboratory Medicine, University of Regensburg, Regensburg, Germany
  16. 16Hohentwielstr. 32, 78250 Tengen, Germany
  17. 17Department of Pathology, Academic Teaching Hospital Bielefeld, Bielefeld, Germany
  1. Correspondence to Professor Dr Matthias Griese, Department of Pediatric Pneumology, Dr. von Hauner Children's Hospital, LMU, German Center for Lung research (DZL), Lindwurmstraße 4, Munich 80337, Germany; matthias.griese{at}


Background 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.

Methods We retrospectively analysed baseline and outcome characteristics of 40 patients with two disease-causing ABCA3 mutations collected between 2001 and 2015.

Results 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.

Conclusions 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.

  • ABCA3
  • Paediatric interstitial lung disease
  • Surfactant protein

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  • Contributors MG designed the study, collected the cases, analysed the data and drafted and revised the manuscript. He is the guarantor of the entire manuscript. CK organised and analysed the data and drafted the manuscript. MKl, MH, MKa, NC, TS, ATA, IC, MP, TS, ST-L, NR, EE, JS, NS, CA, CK and MG contributed and evaluated patients and performed chart review. RZ, DR and TW performed laboratory and immunohistochemical analyses, FB and SR performed the histological investigations, VT the radiological investigations. CA and PL performed genetic analysis and contributed to the long-term collection of subjects. All contributors read and critically revised the manuscript and agreed to the final version of the manuscript.

  • Funding The work of MG was supported by the Deutsche Forschungsgemeinschaft Gr970/8-1, chILD-EU (FP7, No. 305653) and the “Else Kröner-Fresenius-Stiftung” grant 2013_A72.

  • Competing interests None declared.

  • Ethics approval Institutional Review Board (EK 026-06), chILD-EU (EK 111-13).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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