title: Clinical, radiological and pathological features of ABCA3 mutations in children.
abstract: BACKGROUND
  Mutations in the ABCA3 gene can result in fatal surfactant deficiency in term newborn infants and chronic interstitial lung disease in older children. Previous studies on ABCA3 mutations have focused primarily on the genetic abnormalities and reported limited clinical information about the resultant disease. A study was undertaken to analyse systematically the clinical presentation, pulmonary function, diagnostic imaging, pathological features and outcomes of children with ABCA3 mutations.
  
  
  METHODS
  The records of nine children with ABCA3 mutations evaluated at Texas Children's Hospital between 1992 and 2005 were reviewed and their current clinical status updated. Previous diagnostic imaging studies and lung biopsy specimens were re-examined. The results of DNA analyses were confirmed.
  
  
  RESULTS
  Age at symptom onset ranged from birth to 4 years. Cough, crackles, failure to thrive and clubbing were frequent findings. Mean lung function was low but tended to remain static. CT scans commonly revealed ground-glass opacification, septal thickening, parenchymal cysts and pectus excavatum. Histopathological patterns included pulmonary alveolar proteinosis, desquamative interstitial pneumonitis and non-specific interstitial pneumonitis, and varied with age. Dense abnormalities of lamellar bodies, characteristic of ABCA3 mutations, were seen by electron microscopy in all adequate specimens. Outcomes varied with the age at which the severity of lung disease warranted open lung biopsy, and some patients have had prolonged survival without lung transplantation.
  
  
  CONCLUSIONS
  The presentation and course of interstitial lung disease due to ABCA3 mutations are variable, and open lung biopsy and genetic testing are warranted early in the evaluation of children with a consistent clinical picture.
authors.affiliation: Texas Children's Hospital, 6621 Fannin, CC1040.00, Houston, TX 77030, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Doan
authors.forename: R P
authors.initials: RP
authors.lastname: Guillerman
authors.forename: M K
authors.initials: MK
authors.lastname: Dishop
authors.forename: L M
authors.initials: LM
authors.lastname: Nogee
authors.forename: C
authors.initials: C
authors.lastname: Langston
authors.forename: G B
authors.initials: GB
authors.lastname: Mallory
authors.forename: M M
authors.initials: MM
authors.lastname: Sockrider
authors.forename: L L
authors.initials: LL
authors.lastname: Fan
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D017563:Lung Diseases, Interstitial / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D008297:Male; D009154:Mutation / Q000235:genetics*; D012129:Respiratory Function Tests / Q000379:methods; D016896:Treatment Outcome
chemical_list: C441524:ABCA3 protein, human; D018528:ATP-Binding Cassette Transporters