Pulmonary surfactant metabolism dysfunction-5 (SMDP5) is an autosomal recessive lung disorder manifest clinically and pathologically as pulmonary alveolar proteinosis. Pulmonary alveolar proteinosis is a rare lung disease characterized by the ineffective clearance of surfactant by alveolar macrophages. This ... Pulmonary surfactant metabolism dysfunction-5 (SMDP5) is an autosomal recessive lung disorder manifest clinically and pathologically as pulmonary alveolar proteinosis. Pulmonary alveolar proteinosis is a rare lung disease characterized by the ineffective clearance of surfactant by alveolar macrophages. This results in the accumulation of surfactant-derived lipoproteinaceous material in the alveoli and terminal bronchioles, causing respiratory failure (summary by Greenhill and Kotton, 2009). For a general phenotypic description and a discussion of genetic heterogeneity of pulmonary surfactant metabolism dysfunction, see SMDP1 (265120).
Dirksen et al. (1997) described an expression defect of the CSF2RB gene in 4 of 7 pediatric patients with pulmonary alveolar proteinosis. Three patients were diagnosed as neonates, and 1 at age 1 month, after presenting with severe ... Dirksen et al. (1997) described an expression defect of the CSF2RB gene in 4 of 7 pediatric patients with pulmonary alveolar proteinosis. Three patients were diagnosed as neonates, and 1 at age 1 month, after presenting with severe respiratory distress. All were ventilation-dependent. Patient cells failed to express normal levels of beta-c, as shown by flow cytometry, and reduced or absent function of beta-c was demonstrated by ligand binding studies and progenitor clonogenic assays. However, molecular analysis of the CSF2RB gene failed to identify pathogenic mutations. Tanaka et al. (2011) reported a Japanese woman, born of consanguineous parents, who developed gradual dyspnea on exertion beginning at age 36 years. Chest radiographs showed diffuse homogeneous ground-glass opacities and paving appearance, and lung biopsy showed accumulation of amorphous eosinophilic material in the alveolar space, consistent with a diagnosis of pulmonary alveolar proteinosis. GMCSF was very high in serum and bronchoalveolar lavage, but autoantibodies to GMCSF were not found. In vitro studies showed that the patient's monocytes failed to differentiate into macrophages after stimulation with GMCSF. There was also a lack of STAT5 (601511) phosphorylation in response to GMCSF or IL3 stimulation, suggesting defective signaling by the common beta subunit of the GMCSF receptor (CSF2RB). Flow cytometry of patient monocytes showed lack of CSF2RB expression, and CSF2RB mRNA was not detected in patient cells. Neither parent was affected.
In a Japanese woman with late-onset hereditary pulmonary alveolar proteinosis, Tanaka et al. (2011) identified a homozygous truncating mutation in the CSF2RB gene (138981.0001). Each unaffected parent was heterozygous for the mutation. Tanaka et al. (2011) speculated that ... In a Japanese woman with late-onset hereditary pulmonary alveolar proteinosis, Tanaka et al. (2011) identified a homozygous truncating mutation in the CSF2RB gene (138981.0001). Each unaffected parent was heterozygous for the mutation. Tanaka et al. (2011) speculated that the late onset in this patient may have been due to compensatory factors such as increased serum GMCSF acting through an intact CSF2RA subunit (306250) or increased levels of other inflammatory cells.