Simultaneous quantification of alpha-aminoadipic semialdehyde, piperideine-6-carboxylate, pipecolic acid and alpha-aminoadipic acid in pyridoxine-dependent epilepsy

• Type of Material: Article
• Authors: Jiao Xue, Peking University; Junjuan Wang, Zhejiang Biosan Biochemical Technologies Co., Ltd.; Pan Gong, Peking University; Minhang Wu, Zhejiang Biosan Biochemical Technologies Co., Ltd.; Wenshuang Yang, Peking University; Shiju Jiang, Peking University; Ye Wu, Peking University; Yuwu Jiang, Peking University; Yuehua Zhang, Peking University; Tatiana Yuzyuk, University of Utah; Hong Li, Emory University; Zhixian Yang, Peking University
• Language: English
• Date: 2019-08-06
• Publisher: Nature Research (part of Springer Nature): Fully open access journals
• Publication Version: Final Published Version
• Copyright Statement: © 2019, The Author(s).
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41598-019-47882-2
• Title of Journal or Parent Work: Scientific Reports
• ISSN: 2045-2322
• Volume: 9
• Issue: 1
• Start Page: 11371
• End Page: 11371
• Grant/Funding Information: This work was supported by National Science Foundation of China (No. 81771393), Beijing Municipal Science & Technology Commission (No. Z171100001017125).
• Keywords: Science & Technology; Science & Technology - Other Topics; SEIZURES; DIAGNOSIS; ANTIQUITIN; PLASMA; Multidisciplinary Sciences; DIETARY LYSINE RESTRICTION; LC-MS/MS; MUTATIONS; ARGININE SUPPLEMENTATION
• Research Categories: Biology, Neuroscience; Health Sciences, Pathology; Chemistry, Biochemistry

Abstract

The measurements of lysine metabolites provide valuable information for the rapid diagnosis of pyridoxine-dependent epilepsy (PDE). Here, we aimed to develop a sensitive method to simultaneously quantify multiple lysine metabolites in PDE, including α-aminoadipic semialdehyde (a-AASA), piperideine-6-carboxylate (P6C), pipecolic acid (PA) and α-aminoadipic acid (α-AAA) in plasma, serum, dried blood spots (DBS), urine and dried urine spots (DUS). Fifteen patients with molecularly confirmed PDE were detected using liquid chromatography-mass spectrometry (LC-MS/MS) method. Compared to the control groups, the concentrations of a-AASA, P6C and the sum of a-AASA and P6C (AASA-P6C) in all types of samples from PDE patients were markedly elevated. The PA and a-AAA concentrations ranges overlapped partially between PDE patients and control groups. The concentrations of all the analytes in plasma and serum, as well as in urine and DUS were highly correlated. Our study provided more options for the diverse sample collection in the biochemical tests according to practical requirements. With treatment modality of newly triple therapy investigated, biomarker study might play important role not only on diagnosis but also on treatment monitoring and fine tuning the diet. The persistently elevated analytes with good correlation between plasma and DBS, as well as urine and DUS made neonatal screening using DBS and DUS possible.