title: Pulmonary alveolar proteinosis in patients with adenosine deaminase deficiency.
abstract: BACKGROUND
  Inherited defects in the function of adenosine deaminase (ADA) cause severe combined immunodeficiency (SCID) and affect many other cells and tissues.
  
  
  OBJECTIVE
  We sought to characterize the frequency and features of pulmonary alveolar proteinosis (PAP) in patients with ADA deficiency.
  
  
  METHODS
  Clinical and laboratory features of all patients with SCID caused by ADA deficiency in a single center were analyzed. Bronchoalveolar lavage (BAL) fluid and lung biopsy specimens were stained with hematoxylin and eosin and periodic acid-Schiff, visualized by means of electron microscopy, and studied for associated infections. As a control group, BAL fluid and biopsy specimens from 22 patients with SCID caused by other genetic abnormalities were similarly assessed.
  
  
  RESULTS
  Among 16 consecutive patients with ADA deficiency, 7 had BAL fluid containing periodic acid-Schiff-positive surfactant-like material with macrophages engulfing degenerating lamellar bodies and/or lung biopsy specimens with alveolar spaces filled with homogeneous granular eosinophilic material and large macrophages. The lung pathology was typical of PAP. Identification of various pathogens coincided with PAP in 3 of these patients. We have diagnosed PAP among patients with ADA deficiency more commonly in the last 10 years than previously (P= .05), likely reflecting increased awareness of this condition. There were no significant differences in the clinical or immunologic characteristics between patients with ADA deficiency with or without PAP. Similar findings of PAP were not found among patients with SCID caused by other genetic abnormalities (P= .001). ADA coupled to polyethylene glycol or allogeneic hematopoietic stem cell transplantation rapidly corrected this pulmonary complication. PAP seems to have contributed to the death of only 1 patient with ADA deficiency.
  
  
  CONCLUSIONS
  ADA deficiency predisposes to the development of PAP, which could be reversed after enzyme replacement or transplantation.
authors.affiliation: Division of Allergy and Clinical Immunology, Hospital for Sick Children and the University of Toronto, Toronto, Ontario, Canada. Eyal.grunebaum@sickkids.ca
authors.forename: Eyal
authors.initials: E
authors.lastname: Grunebaum
authors.forename: Ernest
authors.initials: E
authors.lastname: Cutz
authors.forename: Chaim M
authors.initials: CM
authors.lastname: Roifman
mesh_terms: D000243:Adenosine Deaminase / Q000172:deficiency / Q000627:therapeutic use; D000361:Agammaglobulinemia / Q000150:complications*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D056947:Enzyme Replacement Therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008168:Lung / Q000473:pathology; D011649:Pulmonary Alveolar Proteinosis / Q000175:diagnosis / Q000209:etiology* / Q000628:therapy; D016511:Severe Combined Immunodeficiency / Q000150:complications*; D014184:Transplantation, Homologous
chemical_list: D000243:Adenosine Deaminase