Interstitial lung disease in a child with a novel mutation of SFTPC successfully treated with lung transplantation
Interstitial lung disease in a child with a novel mutation of SFTPC successfully treated with lung transplantation
Abstract
The gene SFTPC encodes a 197-amino-acid precursor surfactant protein C (proSP-C), which is cleaved into a mature 3.7kDa surfactant protein C (SP-C). Mutations of SFTPC have been reported to be associated with neonatal respiratory distress syndrome (RDS) or childhood interstitial lung disease (ILD). In this report we present a child who had suffered neonatal RDS and developed ILD due to a novel heterozygous SFTPC mutation (c.203T>A, p.Val68Asp), who was successfully treated with lung transplantation. A 20-month-old patient presented at our emergency room with chronic tachypnea, cough, and failure to thrive. She was born at term after an uneventful pregnancy, but developed respiratory distress within hours. She was intubated and was given 2 doses of exogenous surfactant, followed by a 1-week course of dexamethasone support. She was successfully weaned off mechanical ventilation, but after discharge from the NICU, she had gradually worsening symptoms of cough, tachypnea and failure to thrive. Since 16 months of age, symptoms aggravated despite treatment with antibiotics and several courses of oral prednisolone. At 20 months of age after no improvement with 2 cycles of methylprednisolone pulse therapy and 2 cycles of IVIG, she visited our hospital for a second opinion. At our hospital, CT scan showed diffuse mosaic pattern with GGO and subpleural cysts that was compatible with interstitial lung disease. VATS lung biopsy revealed nonspecific interstitial pneumonia with eosinophilic proteinaceous material in alveolar space. Genetic analysis was done, but results were not available at the time. She was listed at KONOS as a lung transplant candidate, and within a week, received bilateral lung transplant from a 30-month-old child. After post-transplant care, she was discharged at room air. We detected a novel c.203T>A, p.Val68Asp mutation of SFTPC, based on the same exon as a known pathogenic mutation p.Glu66Lys. To our knowledge, this is the first genetically diagnosed SFTPC mutation causative of a childhood ILD in Korea. Had we been able to detect the mutation earlier, we could have spared the need for a VATS lung biopsy. We propose that if a patient presents with full-term neonatal RDS and childhood ILD, surfactant protein deficiency should be considered to spare unnecessary invasive studies and initiate early treatment.