Familial interstitial disease with I73T mutation: A mid- and long-term study
Related Experiment Video
Updated: Jun 26, 2026
Immunoglobulin Gene Sequence Analysis In Chronic Lymphocytic Leukemia: From Patient Material To Sequence Interpretation
Published on: November 26, 2018
Rola Abou Taam1, Francis Jaubert, Sophie Emond
1Université Paris Descartes, Assistance Publique des Hôpitaux de Paris, Hôpital Necker Enfants Malades, Paris, France. rola.aboutaam@nck.aphp.fr
Insights
Chronic interstitial lung disease in children with the I73T mutation shows variable respiratory involvement. Genetic screening for surfactant protein gene mutations is valuable for diagnosis and management.
Area of Science:
- Pulmonology
- Genetics
- Pediatrics
Background:
- Chronic interstitial lung disease (chILD) in children can be associated with genetic mutations.
- The I73T mutation in surfactant protein genes is a rare cause of chILD.
Purpose of the Study:
- To describe the long-term course and management of chILD associated with the I73T mutation in a pediatric cohort.
- To evaluate the clinical, radiological, and histological features of this condition.
Main Methods:
- Retrospective and prospective analysis of clinical, radiological, and histological data from one family with five children and two adults.
- Genetic screening for surfactant protein gene mutations.
- Bronchoalveolar lavage (BAL) and lung biopsies in affected children.
Main Results:
- Children presented with respiratory symptoms around 6 months of age.
- Treatment with methylprednisolone pulses, oral prednisolone, hydroxychloroquine, and mycophenolate mofetil led to clinical improvement and cessation of oxygen support.
- CT scans showed initial ground-glass opacities evolving to cysts with clinical improvement.
Conclusions:
- The I73T mutation leads to variable respiratory involvement and prognosis in children.
- Genetic screening is crucial for diagnosing chILD related to surfactant protein gene mutations.
- Early diagnosis and appropriate management can significantly improve outcomes.
Objectives:
To describe the long-term course and the management in children of chronic interstitial lung disease associated with I73T 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.
