Gabriella Allegri, Martin Poms, Nadia Zürcher, Véronique Rüfenacht, Nicole Rimann, Déborah Mathis, Beat Thöny, Matthias Gautschi, Ralf A Husain, Daniela Karall, Karolina Orchel-Szastak, Francesco Porta, Dominique Roland, Barbara Siri, Carlo Dionisi-Vici, René Santer, Johannes Häberle
{"title":"利用稳定同位素对尿源性疾病进行表征和治疗监测。","authors":"Gabriella Allegri, Martin Poms, Nadia Zürcher, Véronique Rüfenacht, Nicole Rimann, Déborah Mathis, Beat Thöny, Matthias Gautschi, Ralf A Husain, Daniela Karall, Karolina Orchel-Szastak, Francesco Porta, Dominique Roland, Barbara Siri, Carlo Dionisi-Vici, René Santer, Johannes Häberle","doi":"10.1038/s44324-025-00051-8","DOIUrl":null,"url":null,"abstract":"<p><p>Urea cycle disorders (UCDs) are a group of rare conditions, possibly life-threatening and without definitive cure besides liver transplantation. Traditional biochemical analyses/biomarkers cannot reliably determine changes in the UC-function from baseline to post-intervention. We describe a UHPLC-HRMS method to assess ureagenesis in plasma and dried blood spots for [<sup>15</sup>N]urea and [<sup>15</sup>N]amino acids, using [<sup>15</sup>N]ammonium chloride as tracer. [<sup>15</sup>N]enrichment of urea and amino acids was studied in controls (<i>n</i> = 22) and patients (<i>n</i> = 59), the latter showing characteristic ureagenesis variations according to their underlying metabolic defect. Follow-up of therapies was successful, as we observed restoration of [<sup>15</sup>N]urea production and lowering of [<sup>15</sup>N]glutamine. There were no adverse events, and only minimal amounts of tracer and samples required with a short sample preparation time and analysis. Thus, the method proved to be safe and efficient to monitor UCD patients of variable severity pre- and post-therapy, being suitable as physiological endpoint for development of therapies.</p>","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":"3 1","pages":"19"},"PeriodicalIF":0.0000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12055570/pdf/","citationCount":"0","resultStr":"{\"title\":\"Characterization and treatment monitoring of ureagenesis disorders using stable isotopes.\",\"authors\":\"Gabriella Allegri, Martin Poms, Nadia Zürcher, Véronique Rüfenacht, Nicole Rimann, Déborah Mathis, Beat Thöny, Matthias Gautschi, Ralf A Husain, Daniela Karall, Karolina Orchel-Szastak, Francesco Porta, Dominique Roland, Barbara Siri, Carlo Dionisi-Vici, René Santer, Johannes Häberle\",\"doi\":\"10.1038/s44324-025-00051-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Urea cycle disorders (UCDs) are a group of rare conditions, possibly life-threatening and without definitive cure besides liver transplantation. Traditional biochemical analyses/biomarkers cannot reliably determine changes in the UC-function from baseline to post-intervention. We describe a UHPLC-HRMS method to assess ureagenesis in plasma and dried blood spots for [<sup>15</sup>N]urea and [<sup>15</sup>N]amino acids, using [<sup>15</sup>N]ammonium chloride as tracer. [<sup>15</sup>N]enrichment of urea and amino acids was studied in controls (<i>n</i> = 22) and patients (<i>n</i> = 59), the latter showing characteristic ureagenesis variations according to their underlying metabolic defect. Follow-up of therapies was successful, as we observed restoration of [<sup>15</sup>N]urea production and lowering of [<sup>15</sup>N]glutamine. There were no adverse events, and only minimal amounts of tracer and samples required with a short sample preparation time and analysis. Thus, the method proved to be safe and efficient to monitor UCD patients of variable severity pre- and post-therapy, being suitable as physiological endpoint for development of therapies.</p>\",\"PeriodicalId\":501710,\"journal\":{\"name\":\"npj Metabolic Health and Disease\",\"volume\":\"3 1\",\"pages\":\"19\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12055570/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"npj Metabolic Health and Disease\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1038/s44324-025-00051-8\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/5/6 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"npj Metabolic Health and Disease","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1038/s44324-025-00051-8","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/5/6 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
Characterization and treatment monitoring of ureagenesis disorders using stable isotopes.
Urea cycle disorders (UCDs) are a group of rare conditions, possibly life-threatening and without definitive cure besides liver transplantation. Traditional biochemical analyses/biomarkers cannot reliably determine changes in the UC-function from baseline to post-intervention. We describe a UHPLC-HRMS method to assess ureagenesis in plasma and dried blood spots for [15N]urea and [15N]amino acids, using [15N]ammonium chloride as tracer. [15N]enrichment of urea and amino acids was studied in controls (n = 22) and patients (n = 59), the latter showing characteristic ureagenesis variations according to their underlying metabolic defect. Follow-up of therapies was successful, as we observed restoration of [15N]urea production and lowering of [15N]glutamine. There were no adverse events, and only minimal amounts of tracer and samples required with a short sample preparation time and analysis. Thus, the method proved to be safe and efficient to monitor UCD patients of variable severity pre- and post-therapy, being suitable as physiological endpoint for development of therapies.