Interstitial lung disease in two brothers with novel compound heterozygous ABCA3 mutations

Eur J Pediatr. 2013 Jul;172(7):953-7. doi: 10.1007/s00431-013-1977-8. Epub 2013 Feb 27.


Mutations in genes critical for surfactant metabolism, including surfactant protein C (SP-C) and ABCA3, are well-recognized causes of interstitial lung disease. Recessive mutations in ABCA3 were first attributed to fatal respiratory failure in full-term neonates, but they are also increasingly being recognized as a cause of respiratory disorders with less severe phenotypes in older children and also adults. Here, we report a 20-month-old boy with interstitial lung disease caused by two distinct ABCA3 mutations. Initial treatment with methylprednisolone was unsuccessful, but the additional administration of hydroxychloroquine was effective. The family history revealed that the patient's older brother had died of idiopathic interstitial lung disease at 6 months of age, suggesting a genetic etiology of the disease. Sequence analyses of SP-C and ABCA3 genes were performed using DNA samples from the patient himself, his parents, and his brother. These analyses revealed novel compound heterozygous mutations in the coding exons of ABCA3 in both the patient and his brother: c.2741A > G, of paternal origin, and c.3715_3716insGGGGGG, of maternal origin. Conclusion Since ABCA3 mutations seem to be a heterogeneous entity with various phenotypes, we recommend genetic testing for mutations in SP-C and ABCA3 genes to be considered in children with unexplained interstitial lung disease.

Publication types

  • Case Reports

MeSH terms

  • ATP-Binding Cassette Transporters / genetics*
  • Fatal Outcome
  • Heterozygote
  • Humans
  • Hydroxychloroquine / therapeutic use*
  • Infant
  • Lung Diseases, Interstitial / drug therapy
  • Lung Diseases, Interstitial / genetics*
  • Male
  • Mutation
  • Phenotype
  • Pulmonary Surfactant-Associated Proteins / genetics*
  • Respiratory Distress Syndrome, Newborn / genetics
  • Sequence Analysis, DNA
  • Siblings


  • ABCA3 protein, human
  • ATP-Binding Cassette Transporters
  • Pulmonary Surfactant-Associated Proteins
  • Hydroxychloroquine