Long-term follow-up and treatment of congenital alveolar proteinosis

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.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.Pulmonary alveolar proteinosis (PAP) is characterized by a substantial and persistent increase in surfactant pool size [1,2]. There are several causes of this rare condition; mouse models with deletion of granulocyte-macrophage-colony stimulating factor (GM-CSF) or the GM-CSF receptor (GM-CSFR) beta-chain showed the first evidence for involved molecularly mechanisms [3,4]. Autoantibodies against GM-CSF, blocking GM-CSF signaling, are the cause for the most frequent form of PAP, mainly found in adults and also called autoimmune PAP [5]. In 2008 the first two families with congenital PAP and