Exploration of urine metabolic biomarkers for new-onset, untreated pediatric epilepsy: A gas and liquid chromatography mass spectrometry-based metabolomics study

IF 1.4 4区 医学 Q4 CLINICAL NEUROLOGY
Tomoyuki Akiyama , Daisuke Saigusa , Takushi Inoue , Chiho Tokorodani , Mari Akiyama , Rie Michiue , Atsushi Mori , Eiji Hishinuma , Naomi Matsukawa , Takashi Shibata , Hiroki Tsuchiya , Katsuhiro Kobayashi
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引用次数: 0

Abstract

Objective

The discovery of objective indicators for recent epileptic seizures will help confirm the diagnosis of epilepsy and evaluate therapeutic effects. Past studies had shortcomings such as the inclusion of patients under treatment and those with various etiologies that could confound the analysis results significantly. We aimed to minimize such confounding effects and to explore the small molecule biomarkers associated with the recent occurrence of epileptic seizures using urine metabolomics.

Methods

This is a multicenter prospective study. Subjects included pediatric patients aged 2 to 12 years old with new-onset, untreated epilepsy, who had had the last seizure within 1 month before urine collection. Controls included healthy children aged 2 to 12 years old. Those with underlying or chronic diseases, acute illnesses, or recent administration of medications or supplements were excluded. Targeted metabolome analysis of spot urine samples was conducted using gas chromatography (GC)- and liquid chromatography (LC)-tandem mass spectrometry (MS/MS).

Results

We enrolled 17 patients and 21 controls. Among 172 metabolites measured by GC/MS/MS and 41 metabolites measured by LC/MS/MS, only taurine was consistently reduced in the epilepsy group. This finding was subsequently confirmed by the absolute quantification of amino acids. No other metabolites were consistently altered between the two groups.

Conclusions

Urine metabolome analysis, which covers a larger number of metabolites than conventional biochemistry analyses, found no consistently altered small molecule metabolites except for reduced taurine in epilepsy patients compared to healthy controls. Further studies with larger samples, subjects with different ages, expanded target metabolites, and the investigation of plasma samples are required.

探索新发、未治疗的小儿癫痫的尿液代谢生物标志物:基于气相色谱和液相色谱质谱法的代谢组学研究。
目的:发现癫痫近期发作的客观指标将有助于确诊癫痫和评估治疗效果。以往的研究存在不足之处,例如纳入了正在接受治疗的患者和有各种病因的患者,这可能会对分析结果造成很大的干扰。我们的目的是尽量减少这种混淆效应,并利用尿液代谢组学研究与近期癫痫发作相关的小分子生物标记物:这是一项多中心前瞻性研究。研究对象包括2至12岁的新发、未经治疗的癫痫小儿患者,他们的最后一次癫痫发作是在尿液采集前1个月内。对照组包括 2 至 12 岁的健康儿童。患有基础疾病或慢性疾病、急性疾病或最近服用过药物或补充剂的儿童不包括在内。采用气相色谱(GC)和液相色谱(LC)-串联质谱法(MS/MS)对定点尿样进行靶向代谢组分析:我们招募了 17 名患者和 21 名对照组。在通过气相色谱/质谱/串联质谱(GC/MS/MS)测定的 172 种代谢物和通过液相色谱/串联质谱(LC/MS/MS)测定的 41 种代谢物中,只有牛磺酸在癫痫组中持续减少。随后,氨基酸的绝对定量也证实了这一发现。结论:尿液代谢组分析比传统的生化分析涵盖更多的代谢物,与健康对照组相比,除了牛磺酸减少外,癫痫患者的小分子代谢物没有发生一致的变化。还需要对更大的样本、不同年龄的受试者、更多的目标代谢物进行进一步研究,并对血浆样本进行调查。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Brain & Development
Brain & Development 医学-临床神经学
CiteScore
3.60
自引率
0.00%
发文量
153
审稿时长
50 days
期刊介绍: Brain and Development (ISSN 0387-7604) is the Official Journal of the Japanese Society of Child Neurology, and is aimed to promote clinical child neurology and developmental neuroscience. The journal is devoted to publishing Review Articles, Full Length Original Papers, Case Reports and Letters to the Editor in the field of Child Neurology and related sciences. Proceedings of meetings, and professional announcements will be published at the Editor''s discretion. Letters concerning articles published in Brain and Development and other relevant issues are also welcome.
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