title: A disorder of surfactant metabolism without identified genetic mutations.
abstract: BACKGROUND
  Surfactant metabolism disorders may result in diffuse lung disease in children.
  
  
  METHODS
  We report a 3-years-old boy with dry cough, progressive hypoxemia, dyspnea and bilateral ground glass opacities at chest high-resolution computed tomography (HRCT) who had no variants in genes encoding surfactant proteins or transcription factors. Lung histology strongly suggested an abnormality of surfactant protein. A 7-month course of pulse intravenous high-dose methylprednisolone plus oral hydroxychloroquine and azithromycin led to gradual weaning from oxygen and oral steroids, and to improvement of cough and dyspnea. Over the follow-up period, hydroxychloroquine and azithromycin were not withdrawn as cough and dyspnea re-appeared at each attempt and disappeared at re-start. At 6 years of age chest HRCT still appeared unchanged, but clinical symptoms or signs were absent.
  
  
  CONCLUSIONS
  In children suspected of inborn errors of pulmonary surfactant metabolism who do not have a recognized genetic mutation, lung biopsy with consistent histology may help physicians to address the definitive diagnosis.
authors.affiliation: Department of Translational Medical Sciences, Federico II University, Via Sergio Pansini, 5 - 80131, Naples, Italy. amina2004@virgilio.it.
authors.forename: Silvia
authors.initials: S
authors.lastname: Montella
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, TX, USA. tjvece@texaschildrens.org.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Vece
authors.affiliation: Department of Pathology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX, USA. cxlangst@texaschildrens.org.
authors.forename: Claire
authors.initials: C
authors.lastname: Langston
authors.affiliation: Division of Genetics and Cell Biology, IRCCS Ospedale San Raffaele, Milano, Italy. carrerapaola9@gmail.com.
authors.forename: Paola
authors.initials: P
authors.lastname: Carrera
authors.affiliation: Department of Pediatrics, Division of Neonatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. lnogee@jhmi.edu.
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Nogee
authors.affiliation: Edward Mallinckrodt Department of Pediatrics, Division of Newborn Medicine, Washington University School of Medicine, St. Louis, MO, USA. ahamvas@luriechildrens.org.|Department of Pediatrics, Division of Neonatology, Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. ahamvas@luriechildrens.org.
authors.forename: Aaron
authors.initials: A
authors.lastname: Hamvas
authors.affiliation: Department of Translational Medical Sciences, Federico II University, Via Sergio Pansini, 5 - 80131, Naples, Italy. manna.ange@gmail.com.
authors.forename: Angelo
authors.initials: A
authors.lastname: Manna
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Cervasio
authors.affiliation: Department of Advanced Biomedical Sciences, Anatomo-Pathology Unit, Federico II University, Naples, Italy. mara.cervasio@tin.it.
authors.forename: Mara
authors.initials: M
authors.lastname: Cervasio
authors.affiliation: Department of Translational Medical Sciences, Federico II University, Via Sergio Pansini, 5 - 80131, Naples, Italy. santamar@unina.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Santamaria
mesh_terms: D001706:Biopsy; D002675:Child, Preschool; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D006801:Humans; D017563:Lung Diseases, Interstitial / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009154:Mutation; D037721:Pulmonary Surfactant-Associated Protein C / Q000235:genetics* / Q000378:metabolism; D014057:Tomography, X-Ray Computed
chemical_list: D037721:Pulmonary Surfactant-Associated Protein C; D004247:DNA