Mutations in the gene for adenosine triphosphate-binding cassette transporter subfamily A member 3 (ABCA3) have been reported in infants and children with surfactant deficiency and interstitial lung disease. We report a case of siblings found to be compound heterozygotes for two novel ABCA3 gene mutations but developing very different course of lung disease. The index case is a baby girl with severe interstitial lung disease that manifested on the first days of life. Her 4-year-old brother carrying the same mutations has no signs of lung disease so far. Our findings suggest the contribution of other genetic, epigenetic and environmental factors to discordant phenotype observed in patients carrying the same mutations in the ABCA3 gene. The clinical course of the index case suggests benefit of combined medical therapy in treating infants with ABCA3 deficiency.
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Adenosine triphosphate-binding cassette transporter subfamily A member 3
Continuous-positive airway pressure
Interstitial lung disease
Intensive care unit
Desquamative interstitial pneumonitis
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The authors thank the parents of the affected children, Dr. Alfred C. Looman for the genetic analyses results and Dr. Tuuli Metsvaht for the helpful comments on the manuscript. Tarmo Annilo is supported by University of Tartu (grant “Center of Translational Genomics”), Estonian Government (grant #SF0180142s08), European Commission through the European Regional Development Fund (grant “Centre of Excellence in Genomics”), Estonian Research Infrastructures Roadmap and FP7 (grant #313010).
Conflict of interest
The authors declare no conflict of interest.
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Hallik, M., Annilo, T. & Ilmoja, M. Different course of lung disease in two siblings with novel ABCA3 mutations. Eur J Pediatr 173, 1553–1556 (2014). https://doi.org/10.1007/s00431-013-2087-3
- Paediatric interstitial lung disease
- Newborn respiratory distress