Neonatal respiratory insufficiency caused by an (homozygous) ABCA3-stop mutation: a systematic evaluation of therapeutic options

Klin Padiatr. 2014 Apr;226(2):53-8. doi: 10.1055/s-0033-1363687. Epub 2014 Mar 14.

Abstract

Background: Autosomal recessive ABCA3 (ATP-binding cassette protein A3) gene mutations have been associated with neonatal respiratory distress and pediatric interstitial lung disease. The clinical course of the disease depends on the underlying mutations. Therefore, knowledge of course, symptoms and treatment of the disease is important.

Patient and methods: A term newborn suffered from progressive respiratory insufficiency, which led to death at the age of 4.8 months. The girl developed interstitial lung disease. Infections as well as structural and functional disorders of the lung were systematically excluded. A homozygous c.4681C > T (Arg 1561 Stop) mutation of the ABCA3 gene was identified. A literature review of the pathophysiology and treatment options of the disease was done. Therapeutic approaches with corticosteroids, macrolide, and hydroxychloroquine did not improve the clinical course.

Results: Therapeutic strategies for chronic interstitial lung disease have been used successfully in cases of a mild clinical course in juvenile patients with ABCA3 gene mutation. In our patient with homozygous ABCA3 gene mutation,they were not effective. Lung transplantation remains as a therapeutic option, but because of donor organ shortage and associated morbidity and mortality it is rarely feasible.

Conclusion: More experience in the treatment of newborns with ABCA3 gene mutations is needed. Randomized, prospective evaluation of the different therapeutic approaches in a specific registry may improve prognosis and treatment of affected individuals.

Publication types

  • Case Reports
  • Review

MeSH terms

  • ATP-Binding Cassette Transporters / genetics*
  • Adrenal Cortex Hormones / therapeutic use
  • Chromosome Aberrations
  • Codon, Terminator / genetics*
  • Fatal Outcome
  • Female
  • Genes, Recessive / genetics
  • Homozygote*
  • Humans
  • Hydroxychloroquine / therapeutic use
  • Infant
  • Infant, Newborn
  • Lung Diseases, Interstitial / drug therapy
  • Lung Diseases, Interstitial / genetics
  • Macrolides / therapeutic use
  • Mutation / genetics*
  • Respiratory Distress Syndrome, Newborn / drug therapy
  • Respiratory Distress Syndrome, Newborn / genetics*
  • Respiratory Insufficiency / drug therapy
  • Respiratory Insufficiency / genetics*
  • Treatment Failure

Substances

  • ABCA3 protein, human
  • ATP-Binding Cassette Transporters
  • Adrenal Cortex Hormones
  • Codon, Terminator
  • Macrolides
  • Hydroxychloroquine