{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:26:51Z","timestamp":1791898011335,"version":"4.3.4"},"reference-count":25,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,9,7]],"date-time":"2020-09-07T00:00:00Z","timestamp":1599436800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005941","name":"Dietmar Hopp Stiftung","doi-asserted-by":"publisher","award":["23011235"],"award-info":[{"award-number":["23011235"]}],"id":[{"id":"10.13039\/501100005941","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000921","name":"European Cooperation in Science and Technology","doi-asserted-by":"publisher","award":["16125 ENTeR\u2010chILD"],"award-info":[{"award-number":["16125 ENTeR\u2010chILD"]}],"id":[{"id":"10.13039\/501100000921","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["GR 970\/9\u20101"],"award-info":[{"award-number":["GR 970\/9\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Pulmonology"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pulmonary alveolar proteinosis (PAP) is a heterogeneous condition with more than 100 different underlying disorders that need to be differentiated to target therapeutic options, which are generally limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The clinical course of two brothers with pathogenic variants in the methionyl\u2010tRNA synthetase (\n                      <jats:italic>MARS)1<\/jats:italic>\n                      gene was compared to previously published patients. Functional studies in patient\u2010derived fibroblasts were performed and therapeutic options evaluated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The younger brother was diagnosed with PAP at the age of 1 year. Exome sequencing revealed the homozygous\n                      <jats:italic>MARS1<\/jats:italic>\n                      variant p.(Arg598Cys), leading to interstitial lung and liver disease (ILLD). At 2 years of age, following surgery hypoglycemia was detected, the pulmonary condition deteriorated, and the patient developed multiorgan failure. Six therapeutic whole lung lavages (WLL) were necessary to improve respiratory insufficiency. Methionine supplementation was started and a high protein diet ensured, leading to complete respiratory recovery. The older brother, homozygous for the same\n                      <jats:italic>MARS1<\/jats:italic>\n                      variant, had a long\u2010known distinct eating preference of methionine\u2010rich food and showed a less severe clinical phenotype. Decreased aminoacylation activity confirmed the pathogenicity of p.(Arg598Cys) in vitro. In agreement with our review of currently published ILLD patients, the presence of hepatopathy, developmental delay, muscular hypotonia, and anemia support the multisystemic character of the disease.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Catabolic events can provoke a severe deterioration of the pulmonary situation in ILLD with a need for repetitive WLL. Although the precise role of oral methionine supplementation and high protein intake are unknown, we observed an apparent treatment benefit, which needs to be evaluated systematically in controlled trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ppul.25031","type":"journal-article","created":{"date-parts":[[2020,8,24]],"date-time":"2020-08-24T19:37:29Z","timestamp":1598297849000},"page":"3057-3066","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Rescue of respiratory failure in pulmonary alveolar proteinosis due to pathogenic\n                    <i>MARS1<\/i>\n                    variants"],"prefix":"10.1002","volume":"55","author":[{"given":"Dominic","family":"Lenz","sequence":"first","affiliation":[{"name":"Division of Neuropediatrics and Pediatric Metabolic Medicine, Center for Pediatric and Adolescent Medicine University Hospital Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirjam","family":"Stahl","sequence":"additional","affiliation":[{"name":"Department of Translational Pulmonology, Translational Lung Research Center Heidelberg (TLRC), German Centre for Lung Research (DZL) University of Heidelberg Heidelberg Germany"},{"name":"Department of Pediatric Pulmonology, Immunology and Intensive Care Medicine Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6610-3756","authenticated-orcid":false,"given":"Elias","family":"Seidl","sequence":"additional","affiliation":[{"name":"Dr. von Haunersches Kinderspital, University of Munich German Center for Lung Research (DZL) Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Sch\u00f6ndorf","sequence":"additional","affiliation":[{"name":"Division of Pediatric Pulmonology and Allergy and Cystic Fibrosis Center, Department of Pediatrics University of Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6909-0003","authenticated-orcid":false,"given":"Heiko","family":"Brennenstuhl","sequence":"additional","affiliation":[{"name":"Division of Neuropediatrics and Pediatric Metabolic Medicine, Center for Pediatric and Adolescent Medicine University Hospital Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Gesenhues","sequence":"additional","affiliation":[{"name":"Dr. von Haunersches Kinderspital, University of Munich German Center for Lung Research (DZL) Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Heinzmann","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Department of Pediatrics University of Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Longerich","sequence":"additional","affiliation":[{"name":"Institute of Pathology University Hospital Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisa I.","family":"Mendes","sequence":"additional","affiliation":[{"name":"Metabolic Unit, Department of Clinical Chemistry, Amsterdam Neuroscience, Amsterdam Gastroenterology &amp; Metabolism, Amsterdam UMC Vrije Universiteit Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Prokisch","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Klinikum rechts der Isar Technical University of Munich Munich Germany"},{"name":"Institute of Human Genetics Helmholtz Zentrum Munich Neuherberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gajja S.","family":"Salomons","sequence":"additional","affiliation":[{"name":"Metabolic Unit, Department of Clinical Chemistry, Amsterdam Neuroscience, Amsterdam Gastroenterology &amp; Metabolism, Amsterdam UMC Vrije Universiteit Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carola","family":"Sch\u00f6n","sequence":"additional","affiliation":[{"name":"Dr. von Haunersches Kinderspital, University of Munich German Center for Lung Research (DZL) Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Desir\u00e9e E. C.","family":"Smith","sequence":"additional","affiliation":[{"name":"Metabolic Unit, Department of Clinical Chemistry, Amsterdam Neuroscience, Amsterdam Gastroenterology &amp; Metabolism, Amsterdam UMC Vrije Universiteit Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3941-8944","authenticated-orcid":false,"given":"Olaf","family":"Sommerburg","sequence":"additional","affiliation":[{"name":"Department of Translational Pulmonology, Translational Lung Research Center Heidelberg (TLRC), German Centre for Lung Research (DZL) University of Heidelberg Heidelberg Germany"},{"name":"Dr. von Haunersches Kinderspital, University of Munich German Center for Lung Research (DZL) Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matias","family":"Wagner","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Klinikum rechts der Isar Technical University of Munich Munich Germany"},{"name":"Institute of Human Genetics Helmholtz Zentrum Munich Neuherberg Germany"},{"name":"Institute of Neurogenomics Helmholtz Zentrum Munich Neuherberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9837-9383","authenticated-orcid":false,"given":"Jens H.","family":"Westhoff","sequence":"additional","affiliation":[{"name":"Department of Pediatrics I, Center for Pediatric and Adolescent Medicine University Hospital Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Reiter","sequence":"additional","affiliation":[{"name":"Dr. von Haunersches Kinderspital, University of Munich German Center for Lung Research (DZL) Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Staufner","sequence":"additional","affiliation":[{"name":"Division of Neuropediatrics and Pediatric Metabolic Medicine, Center for Pediatric and Adolescent Medicine University Hospital Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0113-912X","authenticated-orcid":false,"given":"Matthias","family":"Griese","sequence":"additional","affiliation":[{"name":"Dr. von Haunersches Kinderspital, University of Munich German Center for Lung Research (DZL) Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,9,7]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-3003.1999.13f36.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra023226"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2017-0610"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.03.010"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi101375d"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1999.3339"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1994.1601"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2013-305049"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1247363"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-9-85"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.14510"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2018.04.005"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-019-1020-x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-0974-4"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2006-924458"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2017-210519"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2431-11-72"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9592.2010.03442.x"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.05.027"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-015-9849-1"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-020-0904-4"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmd2.12092"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2005.08.004"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.01342"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-018-0048-y"}],"container-title":["Pediatric Pulmonology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ppul.25031","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ppul.25031","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ppul.25031","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T06:39:51Z","timestamp":1693895991000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ppul.25031"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,7]]},"references-count":25,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2020,11]]}},"alternative-id":["10.1002\/ppul.25031"],"URL":"https:\/\/doi.org\/10.1002\/ppul.25031","archive":["Portico"],"relation":{},"ISSN":["8755-6863","1099-0496"],"issn-type":[{"value":"8755-6863","type":"print"},{"value":"1099-0496","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,7]]},"assertion":[{"value":"2020-06-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}