Surfactant deficiency syndrome in an infant with a C-terminal frame shift in ABCA3: A case report

Pediatr Pulmonol. 2018 May;53(5):E12-E14. doi: 10.1002/ppul.23994. Epub 2018 Mar 22.

Abstract

Deficiency in ATP binding cassette A3 (ABCA3) causes neonatal respiratory distress, hypoxemic respiratory failure, and interstitial lung disease. ABCA3 transports phospholipids into the lamellar bodies of type II alveolar cells, a critical step in alveolar surfactant production. We report a term infant with ABCA3 surfactant deficiency syndrome with the E292V (c.875A>T; p.Glu292Val) mutation in trans with a novel C-terminal frame shift mutation (c.4938delC; p.Met1647fs). This mutation removes the final 58 amino acids and substitutes 33 incorrect amino acids. The frame shift spares membrane spanning and nucleotide binding domains, but disrupts a highly conserved C-terminal domain, which includes sequence motifs necessary for the function of human paralogs ABCA1, ABCA4, and the bacterial homolog DrrA. This observation suggests the C-terminal domain is also required for normal function of ABCA3.

Keywords: ABCA3; childhood; genetics; interstitial lung disease (ILD); surfactant biology and pathophysiology.

Publication types

  • Case Reports

MeSH terms

  • ATP-Binding Cassette Transporters / genetics*
  • DNA Mutational Analysis
  • Frameshift Mutation / genetics*
  • Gastroscopy / methods*
  • Humans
  • Infant, Newborn
  • Male
  • Pulmonary Surfactant-Associated Proteins / deficiency*
  • Pulmonary Surfactant-Associated Proteins / genetics
  • Respiratory Distress Syndrome, Newborn / diet therapy
  • Respiratory Distress Syndrome, Newborn / genetics
  • Respiratory Distress Syndrome, Newborn / physiopathology*
  • Treatment Outcome

Substances

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