title: Pulmonary alveolar proteinosis in children on La Réunion Island: a new inherited disorder?
abstract: BACKGROUND
  Pulmonary alveolar proteinosis (PAP) is very rare in children. Only a few small series have been published, with little information about long-term progression. The objective of our study was to describe the clinical, radiological and pathological features, and the long-term course of PAP in a cohort of 34 children from La Réunion Island.
  
  
  METHODS
  Data were retrospectively collected from medical files. Radiological and pathological elements were reviewed by two pediatric radiologists and three pathologists, respectively.
  
  
  RESULTS
  Thirteen cases were familial and 32/34 (94%) cases were family connected. Disease onset occurred in the first six months of life in 82% of the patients. Thoracic computed tomography scans showed the typical "crazy-paving" pattern in 94% of cases. Respiratory disease was associated with a liver disorder, with the detection of liver enlargement at diagnosis in 56% of cases. The course of the disease was characterized by frequent progression to chronic respiratory insufficiency, accompanied by the appearance of cholesterol granulomas and pulmonary fibrosis. Overall prognosis was poor, with a mortality of 59% and an overall five-year survival rate from birth of 64%. Whole-lung lavages were performed in 21 patients, with no significant effect on survival. Liver disease progressed to cirrhosis in 18% of children, with no severe complication.
  
  
  CONCLUSIONS
  PAP in children from la Réunion Island is characterized by an early onset, associated liver involvement, poor prognosis and frequent progression to lung fibrosis, despite whole-lung lavages treatment. The geographic clustering of patients and the detection of many familial links between most of the cases strongly suggest a genetic etiology, with an autosomal recessive mode of inheritance.
authors.forename: Laurent
authors.initials: L
authors.lastname: Enaud
authors.affiliation: Service de Pneumologie Pédiatrique, AP-HP, Hôpital Necker-Enfants Malades, service de Pneumologie Pédiatrique, Centre de Référence pour les Maladies Respiratoires Rares de l'Enfant, 149-161 rue de Sèvres, 75015 Paris, France. alice.hadchouel-duverge@nck.aphp.fr.
authors.forename: Alice
authors.initials: A
authors.lastname: Hadchouel
authors.forename: Aurore
authors.initials: A
authors.lastname: Coulomb
authors.forename: Laureline
authors.initials: L
authors.lastname: Berteloot
authors.forename: Florence
authors.initials: F
authors.lastname: Lacaille
authors.forename: Liliane
authors.initials: L
authors.lastname: Boccon-Gibod
authors.forename: Vincent
authors.initials: V
authors.lastname: Boulay
authors.forename: Françoise
authors.initials: F
authors.lastname: Darcel
authors.forename: Matthias
authors.initials: M
authors.lastname: Griese
authors.forename: Mélinée
authors.initials: M
authors.lastname: Linard
authors.forename: Malek
authors.initials: M
authors.lastname: Louha
authors.forename: Michel
authors.initials: M
authors.lastname: Renouil
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Rivière
authors.forename: Bruno
authors.initials: B
authors.lastname: Toupance
authors.forename: Virginie
authors.initials: V
authors.lastname: Verkarre
authors.forename: Christophe
authors.initials: C
authors.lastname: Delacourt
authors.forename: Jacques
authors.initials: J
authors.lastname: de Blic
mesh_terms: D002648:Child; D002675:Child, Preschool; D005260:Female; D005602:France; D006801:Humans; D007223:Infant; D008297:Male; D010375:Pedigree; D011649:Pulmonary Alveolar Proteinosis / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics; D011859:Radiography; D012189:Retrospective Studies