RT Journal Article
SR Electronic
T1 Methionine supplementation for multi-organ dysfunction in MetRS-related pulmonary alveolar proteinosis
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 2101554
DO 10.1183/13993003.01554-2021
A1 Alice Hadchouel
A1 David Drummond
A1 Clément Pontoizeau
A1 Laura Aoust
A1 Maria-Margarita Hurtado Nedelec
A1 Jamel El Benna
A1 Elsa Gachelin
A1 Caroline Perisson
A1 Clémentine Vigier
A1 Manuel Schiff
A1 Florence Lacaille
A1 Thierry Jo Molina
A1 Laureline Berteloot
A1 Sylvain Renolleau
A1 Chris Ottolenghi
A1 Jean-Marc Tréluyer
A1 Jacques de Blic
A1 Christophe Delacourt
YR 2021
UL http://erj.ersjournals.com/content/early/2021/08/19/13993003.01554-2021.abstract
AB Introduction Pulmonary alveolar proteinosis related to mutations in the methionine tRNA synthetase (MARS1) gene is a severe, early-onset disease that results in death before the age of 2 years in one-third of patients. It is associated with a liver disease, growth failure and systemic inflammation. As methionine supplementation in yeast models restored normal enzymatic activity of the synthetase, we studied the tolerance, safety and efficacy of daily oral methionine supplementation in patients with severe and early disease.Methods Four patients received methionine supplementation and were followed for respiratory, hepatic, growth, and inflammation-related outcomes. Their course was compared to those of historical controls. Reactive oxygen species (ROS) production by patient monocytes before and after methionine supplementation was also studied.Results Methionine supplementation was associated with respiratory improvement, clearance of the extracellular lipoproteinaceous material, and discontinuation of whole-lung lavage in all patients. The three patients who required oxygen or non-invasive ventilation could be weaned off within 60 days. Liver dysfunction, inflammation, and growth delay also improved or resolved. At a cellular level, methionine supplementation normalised the production of reactive oxygen species by peripheral monocytes.Conclusion Methionine supplementation was associated with important improvements in children with pulmonary alveolar proteinosis related to mutations in the MARS1 gene. This study paves the way for similar strategies for other tRNA synthetase deficiencies.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Alice HADCHOUEL reports grants from APHP, grants from Fonds de Recherche en Santé Respiratoire - Fondation du Souffle, during the conduct of the study; In addition, Dr. HADCHOUEL has a patent EP 21 305 689.8 pending.Conflict of interest: Dr. David Drummond has nothing to disclose.Conflict of interest: Dr. Clément Pontoizeau has nothing to disclose.Conflict of interest: Dr. Laura Aoust has nothing to disclose.Conflict of interest: Dr. Maria-Margarita Hurtado Nedelec has nothing to disclose.Conflict of interest: Dr. Jamel El benna has nothing to disclose.Conflict of interest: Dr. Elsa Gachelin has nothing to disclose.Conflict of interest: Dr. Caroline Perisson has nothing to disclose.Conflict of interest: Dr. Clémentine Vigier has nothing to disclose.Conflict of interest: Dr. Manuel Schiff has nothing to disclose.Conflict of interest: Dr. Florence Lacaille has nothing to disclose.Conflict of interest: Dr. Thierry Jo Molina has nothing to disclose.Conflict of interest: Dr. Laureline Berteloot has nothing to disclose.Conflict of interest: Dr. Sylvain Renolleau has nothing to disclose.Conflict of interest: Dr. Chris Ottolenghi has nothing to disclose.Conflict of interest: Dr. Jean-Marc Tréluyer has nothing to disclose.Conflict of interest: Dr. Jacques de Blic has nothing to disclose.Conflict of interest: Dr. Christophe Delacourt has nothing to disclose.