title: Long-term follow-up and treatment of congenital alveolar proteinosis.
abstract: BACKGROUND
  Clinical presentation, diagnosis, management and outcome of molecularly defined congenital pulmonary alveolar proteinosis (PAP) due to mutations in the GM-CSF receptor are not well known.
  
  
  METHODS
  A 2 1/2 years old girl was diagnosed as having alveolar proteinosis. Whole lung lavages were performed with a new catheter balloon technique, feasible in small sized airways. Because of some interstitial inflammation in the lung biopsy and to further improve the condition, empirical therapy with systemic steroids and azathioprin, and inhaled and subcutaneous GMCSF, were used. Based on clinical measures, total protein and lipid recovered by whole lung lavages, all these treatments were without benefit. Conversely, severe respiratory viral infections and an invasive aspergillosis with aspergilloma formation occurred. Recently the novel homozygous stop mutation p.Ser25X of the GMCSF receptor alpha chain was identified in the patient. This mutation leads to a lack of functional GMCSF receptor and a reduced response to GMCSF stimulation of CD11b expression of mononuclear cells of the patient. Subsequently a very intense treatment with monthly lavages was initiated, resulting for the first time in complete resolution of partial respiratory insufficiency and a significant improvement of the overall somato-psychosocial condition of the child.
  
  
  CONCLUSIONS
  The long term management from early childhood into young adolescence of severe alveolar proteinosis due to GMCSF receptor deficiency requires a dedicated specialized team to perform technically demanding whole lung lavages and cope with complications.
authors.affiliation: Dr. von Haunersches Kinderspital, University of Munich, Munich, Germany. Matthias.griese@med.uni-muenchen.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Griese
authors.forename: Jan
authors.initials: J
authors.lastname: Ripper
authors.forename: Anke
authors.initials: A
authors.lastname: Sibbersen
authors.forename: Pia
authors.initials: P
authors.lastname: Lohse
authors.forename: Peter
authors.initials: P
authors.lastname: Lohse
authors.forename: Frank
authors.initials: F
authors.lastname: Brasch
authors.forename: Andrea
authors.initials: A
authors.lastname: Schams
authors.forename: Asli
authors.initials: A
authors.lastname: Pamir
authors.forename: Bianca
authors.initials: B
authors.lastname: Schaub
authors.forename: Oliver J
authors.initials: OJ
authors.lastname: Muensterer
authors.forename: Carola
authors.initials: C
authors.lastname: Schön
authors.forename: Judith
authors.initials: J
authors.lastname: Glöckner-Pagel
authors.forename: Thomas
authors.initials: T
authors.lastname: Nicolai
authors.forename: Karl
authors.initials: K
authors.lastname: Reiter
authors.forename: Andreas
authors.initials: A
authors.lastname: Hector
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D001379:Azathioprine / Q000627:therapeutic use; D018893:Bronchoalveolar Lavage; D002648:Child; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008168:Lung / Q000000981:diagnostic imaging; D009154:Mutation; D011649:Pulmonary Alveolar Proteinosis / Q000151:congenital* / Q000235:genetics / Q000628:therapy*; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics; D011994:Recombinant Proteins; D012131:Respiratory Insufficiency / Q000209:etiology / Q000628:therapy; D014057:Tomography, X-Ray Computed
chemical_list: D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D001379:Azathioprine