C62-07 Genetic Surfactant Dysfunction in Infancy: A Pathogenic Sftpc Splicing Variant Presenting as Severe Viral Bronchiolitis

Abstract Background Interstitial lung disease (ILD) in infants represents a heterogeneous group of rare disorders with complex genetic and inflammatory mechanisms. Mutations in surfactant protein genes, particularly SFTPC, can lead to surfactant dysfunction and progressive respiratory failure. This report describes an uncommon case of surfactant protein C deficiency revealed after an acute viral bronchiolitis episode in a three-month-old infant, emphasizing the relevance of integrating clinical, radiological, and genetic findings for accurate diagnosis and management. Case Presentation A three-month-old male infant presented with rhinorrhea and progressive respiratory distress. On admission to the Pediatric Intensive Care Unit, he exhibited severe type I respiratory failure (oxygen saturation 92% on 0.5 L/min oxygen) and multilobar pneumonia confirmed by imaging and a positive FilmArray panel for Rhinovirus/Enterovirus. Initial management included high-flow nasal cannula oxygen therapy (FiO2 40%) and systemic corticosteroids, resulting in clinical improvement. However, persistent tachypnea after corticosteroid tapering raised suspicion for an underlying interstitial process. High-resolution chest CT revealed ground-glass opacities and subsegmental atelectasis, suggestive of early interstitial inflammation. Genetic testing (targeted exome sequencing) identified a heterozygous pathogenic SFTPC variant (c.202-2AG) affecting splicing on chromosome 8. This mutation alters pro-SP-C folding in type II pneumocytes, causing endoplasmic reticulum stress, apoptosis, and diffuse alveolar damage. Discussion This case illustrates how an acute viral infection may unmask an underlying surfactant dysfunction disorder. Rhinovirus binds to ICAM-1 receptors on respiratory epithelial cells, triggering IL-6 and IL-8 release, epithelial necrosis, and submucosal edema. In the context of SFTPC mutation, this inflammatory insult likely exacerbated surfactant dysfunction. The persistent tachypnea and interstitial imaging pattern were consistent with pediatric ILD associated with surfactant protein deficiency. Management included inhaled corticosteroids, bronchodilators, macrolide therapy for its immunomodulatory and antifibrotic effects, and bacterial lysates as immune support. The patient showed gradual improvement with no recurrent infections during follow-up. Conclusion This case highlights the importance of considering genetic surfactant disorders in infants with atypical evolution after viral bronchiolitis. The coexistence of viral injury and SFTPC mutation can precipitate early-onset interstitial lung disease. A multidisciplinary diagnostic approach integrating clinical, imaging, and molecular data is essential for precise diagnosis and tailored management. Genetic counseling and long-term respiratory follow-up are recommended due to the variable prognosis associated with SFTPC-related ILD. This abstract is funded by: None