Pathogenesis, Presentation, Diagnosis, and Therapy

Rationale:Weidentifieda6-year-oldgirlwithpulmonaryalveolarproteinosis(PAP),impairedgranulocyte-macrophagecolony‐stimulating factor (GM-CSF) receptor function, and increased GM-CSF. Objectives: Increased serum GM-CSF may be useful to identify individuals with PAP caused by GM-CSF receptor dysfunction. Methods: We screened 187 patients referred to us for measurement of GM-CSF autoantibodies to diagnose autoimmune PAP. Five were childrenwithPAPandincreasedserumGM-CSFbutwithoutGM-CSF autoantibodies or any disease causing secondary PAP; all were studied with family members, subsequently identified patients, and controls. Measurement and Main Results: Eight children (seven female, one male) were identified with PAP caused by recessive CSF2RA mutations. Six presented with progressive dyspnea of insidious onset at 4.8 6 1.6 years and two were asymptomatic at ages 5 and 8 years. Radiologicandhistopathologicmanifestationsweresimilartothose