Dr. von Haunersches Kinderspital, University of Munich, Munich, Germany.
BMC Pediatr. 2011 Aug 17;11:72. doi: 10.1186/1471-2431-11-72.
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.
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.
由于 GM-CSF 受体突变导致的分子定义的先天性肺泡蛋白沉积症（PAP）的临床表现、诊断、治疗和转归尚不清楚。
一名 2 岁半的女孩被诊断为肺泡蛋白沉积症。使用新的气囊导管技术进行全肺灌洗，该技术适用于小气道。由于肺活检中有一些间质炎症，为了进一步改善病情，我们经验性地使用了全身类固醇和硫唑嘌呤、吸入和皮下 GMCSF 治疗。基于临床措施、全肺灌洗中总蛋白和脂质的恢复情况，所有这些治疗都没有效果。相反，发生了严重的呼吸道病毒感染和侵袭性曲霉病并形成曲霉肿。最近，在患者中发现了 GM-CSF 受体α链的新型纯合终止突变 p.Ser25X。该突变导致 GM-CSF 受体功能缺失和患者单核细胞对 GMCSF 刺激的 CD11b 表达反应降低。随后，我们开始进行每月一次的强烈灌洗治疗，这是首次完全缓解部分呼吸功能不全，并显著改善了患儿的整体身体-心理社会状况。
GM-CSF 受体缺乏导致的严重肺泡蛋白沉积症从幼儿期到青少年期的长期管理需要一个专门的专业团队来进行技术要求高的全肺灌洗，并应对并发症。
