Familial Interstitial Disease With 173T Mutation: A Mid- and Long-Term Study

Objectives: To describe the long-term course and the management in children of chronic interstitial lung disease associated with 173T mutation. Materials and Methods: Clinical, radiological, and histological data from one family including five children and two adults were analyzed retrospectively for three patients and prospectively for the others. Results: Mean age of onset of respiratory symptoms for children was 6 months (2-15 months). The follow up was 14 months to 15 years (mean 55 months). The children were treated by intravenous high dose methylprednisolone pulses (6-15, mean 12). Four received oral prednisolone (mean 16 months) and hydroxychloroquine, one of these had additional mycophenolate mofetil. One adult with mild respiratory symptoms in infancy and another who was symptom free were also diagnosed. Both of them received no treatment. BAL fluids were obtained in all children: pro-SPC and SPB were positive in all. Lung biopsies were performed in two children respectively at 7 months, showing interstitial pneumonia features with endoluminal macrophage and type II alveolar cells hyperplasia, and at 33 months, showing subpleural microbullae, areas of interstitial pneumonia and type II alveolar cells hyperplasia. Immunohistochemistry showed for both an increased SPB and TTF1 staining in type II cells nuclei and a faint staining for pro-SPC and for ABCA3. Genetic diagnosis obviated the need for biopsy in other cases. The clinical status progressively improved and oxygen supplementation could be stopped after 3-14 months (mean 9 months). The CT scans initially showed ground glass opacities, then reduction in the ground glass pattern associated with clinical improvement and development of cysts. Conclusion: This kindred illustrates the variability of respiratory involvement and prognosis. It confirms the value of genetic screening for surfactant protein genes mutations. Pediatr Pulmonol. 2009; 44:167-175. (c) 2009 Wiley-Liss, Inc.