arginase deficiency branched-chain amino acids guanidino compounds metabolomics urea cycle disorder
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摘要

PURPOSE:Untargeted metabolomic analysis is increasingly being used in the screening and management of individuals with inborn errors of metabolism (IEM). We aimed to test whether untargeted metabolomic analysis in plasma might be useful for monitoring the disease course and management of urea cycle disorders (UCDs).
METHODS:Untargeted mass spectrometry-based metabolomic analysis was used to generate z-scores for more than 900 metabolites in plasma from 48 individuals with various UCDs. Pathway analysis was used to identify common pathways that were perturbed in each UCD.
RESULTS:Our metabolomic analysis in plasma identified multiple potentially neurotoxic metabolites of arginine in arginase deficiency and, thus, may have utility in monitoring the efficacy of treatment in arginase deficiency. In addition, we were also able to detect multiple biochemical perturbations in all UCDs that likely reflect clinical management, including metabolite alterations secondary to dietary and medication management.
CONCLUSION:In addition to utility in screening for IEM, our results suggest that untargeted metabolomic analysis in plasma may be beneficial for monitoring efficacy of clinical management and off-target effects of medications in UCDs and potentially other IEM.

译文

目的: 非靶向代谢组学分析越来越多地被用于筛查和管理先天代谢错误个体 (IEM)。我们旨在测试血浆中的非靶向代谢组学分析是否有助于监测尿素循环障碍 (UCDs) 的病程和管理。
方法: 使用基于非靶向质谱的代谢组学分析来生成来自 48 个具有不同 ucd 个体的血浆中 900 多种代谢物的 z 值。通路分析被用来确定在每个 UCD 中被扰动的共同通路。
结果: 我们在血浆中的代谢组学分析确定了精氨酸酶缺乏症中精氨酸的多种潜在神经毒性代谢物,因此,可能有助于监测精氨酸酶缺乏症的治疗效果。此外,我们还能够检测到所有 ucd 中可能反映临床管理的多种生化扰动,包括膳食和药物管理继发的代谢物改变。
结论: 除了在 IEM 筛查中的效用, 我们的结果表明,血浆中的非靶向代谢组学分析可能有利于监测 ucd 和潜在的其他 IEM 中临床管理和药物脱靶效应的疗效。

Urea cycle disorders

内分泌 遗传性疾病 疾病
概述  :  

尿素循环系统疾病(UCD)是一种罕见的疾病,会导致机体难以从体内清除消化后的废物。UCD是遗传性疾病,在儿童和成人中均会发生,它可以从父级传递到子级,这些疾病是由于基因突变导致氮代谢缺陷而发展的UCD非常罕见,每3万个新生儿中就有1个发生这种情况。疾病的发作可以是新生儿发作或晚期发作。大约69%的疾病在新生儿期后发展。对于新生儿而言,该疾病将导致他们在出生后的头36-48小时内致命。病理机制这是从父母传给孩子的遗传疾病,婴儿若患上这种病,他们必须从父母双方那里获得缺陷基因。如果父母双方都有缺

urea   英 /jʊˈriːə/   美 /jʊˈriːə/

释    义   n. [肥料] 尿素

例    句   This paper introduces the synthesis and usage of urea Peroxide, and analyzes its prospect. 本文介绍了过氧化尿素的合成和用途,并着重分析了其发展前景。

 

cycle   英 /ˈsaɪkl/   美 /ˈsaɪkl/

释    义   n. 循环;周期;自行车;整套;一段时间

               vt. 使循环;使轮转

               vi. 循环;骑自行车;轮转

同根词   cyclical adj. 周期的,循环的

               cycling n. 骑脚踏车消遣;骑脚踏车兜风

例    句   At the beginning of each instruction cycle, the CPU fetches an instruction from memory.在每个指令周期的开始,CPU都从内存中取一条指令。

 

disorders   美 /dɪs'ɔrdɚ/

释    义   n. 无秩序,混乱;小病(disorder的复数形式)

               v. [电子] 扰乱(disorder的单三形式)

例    句   Sleep disorders are conditions that affect how much and how well you sleep.睡眠障碍是影响你睡眠时间多少和睡眠好坏的情况。

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