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

  • Sci Rep. 2019 Aug 6;9(1):11371. doi: 10.1038/s41598-019-47882-2.
Jiao Xue  1 ,  Junjuan Wang  2 ,  Pan Gong  1 ,  Minhang Wu  2 ,  Wenshuang Yang  3 ,  Shiju Jiang  3 ,  Ye Wu  1 ,  Yuwu Jiang  1 ,  Yuehua Zhang  1 ,  Tatiana Yuzyuk  4  5 ,  Hong Li  6 ,  Zhixian Yang  7
Affiliations
  • 1. Department of Pediatrics, Peking University First Hospital, Beijing, China.
  • 2. Zhejiang Biosan Biochemical Technologies Co., Ltd, Zhejiang, China.
  • 3. Department of Clinical Laboratory, Peking University First Hospital, Beijing, China.
  • 4. Department of Pathology, University of Utah, Salt Lake City, UT, USA.
  • 5. ARUP Laboratories, ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT, USA.
  • 6. Department of Human Genetics, Emory University, School of Medicine, America, Atlanta, USA.
  • 7. Department of Pediatrics, Peking University First Hospital, Beijing, China. [email protected].
PMID: 31388081 DOI: 10.1038/s41598-019-47882-2
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.