title: Neonatal respiratory insufficiency caused by an (homozygous) ABCA3-stop mutation: a systematic evaluation of therapeutic options.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Neonatology, Children's Hospital of the University Medical Center of the Johannes Gutenberg University Mainz, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Winter
authors.affiliation: Neonatology, Children's Hospital of the University Medical Center of the Johannes Gutenberg University Mainz, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Essmann
authors.affiliation: Neonatology, Children's Hospital of the University Medical Center of the Johannes Gutenberg University Mainz, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Kidszun
authors.affiliation: Institute for Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Aslanidis
authors.affiliation: Pediatric Clinic and Policlinic, Dr. von Hauner Children's Hospital, University Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Griese
authors.affiliation: Pediatric Pulmonology, Children's Hospital of the University Medical Center of the Johannes -Gutenberg University Mainz, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Poplawska
authors.affiliation: Neonatology, Children's Hospital of the University Medical Center of the Johannes Gutenberg University Mainz, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Bartsch
authors.affiliation: Institute for Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Schmitz
authors.affiliation: Neonatology, Children's Hospital of the University Medical Center of the Johannes Gutenberg University Mainz, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Mildenberger
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D002869:Chromosome Aberrations; D018388:Codon, Terminator / Q000235:genetics*; D017809:Fatal Outcome; D005260:Female; D005808:Genes, Recessive / Q000235:genetics; D006720:Homozygote; D006801:Humans; D006886:Hydroxychloroquine / Q000627:therapeutic use; D007223:Infant; D007231:Infant, Newborn; D017563:Lung Diseases, Interstitial / Q000188:drug therapy / Q000235:genetics; D018942:Macrolides / Q000627:therapeutic use; D009154:Mutation / Q000235:genetics*; D012127:Respiratory Distress Syndrome, Newborn / Q000188:drug therapy / Q000235:genetics*; D012131:Respiratory Insufficiency / Q000188:drug therapy / Q000235:genetics*; D017211:Treatment Failure
chemical_list: C441524:ABCA3 protein, human; D018528:ATP-Binding Cassette Transporters; D000305:Adrenal Cortex Hormones; D018388:Codon, Terminator; D018942:Macrolides; D006886:Hydroxychloroquine