Characteristics of disorders associated with genetic mutations of surfactant protein C

Abstract

Initial diagnosis is based on clinical presentation, radiological features and BALF analysis, but the definitive diagnosis requires genetic analysis. Although progressive improvement was seen in most patients, the development of new therapeutic strategies with minimal side effects is needed.

Clinical and ultrastructural spectrum of diffuse lung disease associated with surfactant protein C mutations

“…Although linker domain mutations have been reported to have a less severe clinical expression than BRICHOS mutation in some series, 7,17 our own data and the literature do not necessarily support this concept. We found three BRICHOS domain rare variants in our series.…”

“…However, even though human SP-C mutations are mono-allelic and both the wild-type and the mutated alleles are transcribed, mature SP-C peptide is not (or barely) detected in lung tissue and bronchoalveolar lavage fluid. 17,36 Overall, these findings and data suggest that surfactant deficiency, owing to a toxic gain-of-function mechanism affecting LB formation and surfactant synthesis, may contribute in part to the pathogenesis in human. In addition, in the three carriers of linker domain mutations in whom lung biopsy was performed (cases no.…”

“…34 Infiltrates and air leaks are frequent complication in acute exacerbations. 17 Focal or diffuse reticulonodular patterns, centrolobular and subpleural nodules and cystic lesions are described in adults. 29,30 We did not observe specific differences in lung histology between our cases, in whom lung biopsy was obtained at a median age of 6 months.…”

An Official American Thoracic Society Clinical Practice Guideline: Classification, Evaluation, and Management of Childhood Interstitial Lung Disease in Infancy

“…66), but only a few studies have addressed BAL findings in specific chILD entities, such as SFTPC mutations (70). The evidence that informed our recommendation was from several case series in which BAL found an infectious etiology in approximately one-half of infants with DLD who were immunosuppressed due to the treatment of malignancy (64) and roughly one-third of immunocompetent infants with diffuse pulmonary infiltrates (64,73,87).…”

“…The prevalence of mutations in SFTPC or ABCA3 are estimated from more than 20 case reports (169)(170)(171)(172) and case series (42,70,151,152,157,167,168,171,(173)(174)(175)(176)(177). Our confidence in the estimates is limited by the potential selection bias inherent in some of these studies, which could have biased the results toward a higher estimated prevalence.…”