RT Journal Article
SR Electronic
T1 Pulmonary alveolar proteinosis due to a novel mutation in CSF2RA
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P3344
VO 40
IS Suppl 56
A1 C. Happle
A1 M. Wetzke
A1 A.M. Dittrich
A1 G. Hansen
A1 N. Schwerk
YR 2012
UL http://erj.ersjournals.com/content/40/Suppl_56/P3344.abstract
AB Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by pulmonary accumulation of surfactant protein. Congenital forms can result from mutations in granulocyte macrophage-colony stimulating factor (GM-CSF) receptor genes, leading to a terminal differentiation block of alveolar macrophages.We present the case of a 3yr-old girl born to consanguineous parents presenting with progressive dyspnoea, cough and failure to thrive. Her arterial oxygen saturation was 80% while breathing ambient air and dropped to 50% during agitation. Chest radiographs showed bilateral opacities, and high-resolution computed tomography (CT) revealed interlobular densification with typical “crazy paving” pattern. Due to a milky, opaque appearance of bronchioalveolar lavage fluid (BALF) and a strongly PAS-positive staining in histology, the diagnosis of PAP was suspected. After whole lung lavage (WLL), significant clinical improvement occurred. Oxygen saturation increased to >90% and follow-up chest radiographs showed partial clearance.Currently, the patient is undergoing WLL every 4-6 weeks. After 10 months of treatment, she has gained 9 kg of weight, visits kindergarten, and has a good quality of life.The patient's serum- and BALF- GM-CSF concentrations were significantly elevated. Functional analyses of neutrophils and monocytes showed significantly reduced GM-CSF responsiveness. Sequencing revealed a novel mutation in exon seven of the GM-CSF receptor alpha chain gene (CSF2RA). Regarding long-term perspectives, hematopoietic stem cell transplantation (HSCT) has to be considered. However, only one case HSCT in paediatric PAP has been described, with fatal outcome due to a transplantation-associated infection.