ABCA3 mutations associated with pediatric interstitial lung disease

Am J Respir Crit Care Med. 2005 Oct 15;172(8):1026-31. doi: 10.1164/rccm.200503-504OC. Epub 2005 Jun 23.


Rationale: ABCA3 is a member of the ATP-binding cassette family of proteins that mediate the translocation of a wide variety of substrates, including lipids, across cellular membranes. Mutations in the gene encoding ABCA3 were recently identified in full-term neonates with fatal surfactant deficiency.

Objective: To test the hypothesis that ABCA3 mutations are not always associated with fatal neonatal lung disease but are a cause of pediatric interstitial lung disease.

Methods: DNA samples were obtained from 195 children with chronic lung disease of unknown etiology. The 30 coding exons of the ABCA3 gene were sequenced in four unrelated children with a referring diagnosis of desquamative interstitial pneumonitis and who were older than 10 years at the time of enrollment.

Results: Three of four patients (ages 16, 23, and 11 years) with desquamative interstitial pneumonitis had ABCA3 mutations identified on both alleles. All three had the same missense mutation (E292V) and a second unique mutation. The E292V mutation was not found on 200 control alleles from adults without lung disease, but seven additional patients of the remaining study patients had the E292V mutation on one allele. Immunohistochemical analysis of surfactant protein expression in three patients revealed a specific staining pattern for surfactant protein-B, which was the same pattern observed in several infants with fatal lung disease due to ABCA3 mutations.

Conclusion: ABCA3 mutations cause some types of interstitial lung disease in pediatric patients.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / genetics*
  • Adolescent
  • Age Distribution
  • Amino Acid Sequence / genetics
  • Case-Control Studies
  • Causality
  • Child
  • Child, Preschool
  • Chronic Disease
  • DNA Mutational Analysis
  • Female
  • Genotype
  • Humans
  • Immunohistochemistry
  • Infant
  • Lung Diseases, Interstitial / diagnosis
  • Lung Diseases, Interstitial / epidemiology
  • Lung Diseases, Interstitial / genetics*
  • Male
  • Molecular Sequence Data
  • Mutation, Missense / genetics*
  • Pedigree
  • Phenotype
  • Pulmonary Surfactant-Associated Protein B / genetics
  • Severity of Illness Index


  • ABCA3 protein, human
  • ATP-Binding Cassette Transporters
  • Pulmonary Surfactant-Associated Protein B