Scholarlink

<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>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Characterization and treatment monitoring of ureagenesis disorders using stable isotopes

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年5月6日

查看全文
  • 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

摘要

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.