Simultaneous Quantification of Alpha-Aminoadipic Semialdehyde, Piperideine-6-Carboxylate, Pipecolic Acid and Alpha-Aminoadipic Acid in Pyridoxine-Dependent Epilepsy
Abstract number :
3.090
Submission category :
2. Translational Research / 2C. Biomarkers
Year :
2018
Submission ID :
501779
Source :
www.aesnet.org
Presentation date :
12/3/2018 1:55:12 PM
Published date :
Nov 5, 2018, 18:00 PM
Authors :
Zhixian Yang, Peking University First Hospital; Jiao Xue, Peking University First Hospital; Pan Gong, Peking University First Hospital; Junjuan Wang, Zhejiang Biosan Biochemical Technologies Co., Ltd; Minhang Wu, Zhejiang Biosan Biochemical Technologies C
Rationale: Monitoring biomarkers could provide valuable information for the diagnosis and treatment of pyridoxine-dependent epilepsy (PDE). Here, we aimed to develop a sensitive method to simultaneously quantification multiple lysine metabolites including a-aminoadipic semialdehyde (a-AASA), piperideine-6-carboxylate (P6C), the sum of AASA and P6C (AASA-P6C), pipecolic acid (PA) and a-aminoadipic acid (a-AAA) in plasma, serum and dried blood spots (DBS), as well as in urine and dried urine spots (DUS). Methods: Fifteen patients with molecularly confirmed PDE were studied. Control samples were collected from the patients with genetic generalized epilepsy, tic disorders or simple upper respiratory infection. All samples were freshly prepared. The concentrations of analytes were determined using liquid chromatography-mass spectrometry (LC-MS/MS) method. Results: Compared to the control groups, the concentrations of a-AASA, P6C and 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. As for each patient, PA and a-AAA could be moderate elevated or within the reference range. The concentrations of all the analytes in plasma and serum, as well as in urine and DUS were highly correlated. The PA, a-AASA and AASA-P6C concentrations were highly correlated between the DBS and plasma samples, but no obvious correlations were found in P6C and a-AAA. Conclusions: Our study provided more options for the diverse sample collection in the biochemical tests according to practical requirements, and made neonatal screening possible. It seemed that DBS and DUS were the best choices for neonatal screening due to its easier to be prepared, stored and transported. No definite correlations were found between the metabolites levels and age, pyridoxine dosage or psychomotor development in PDE patients. Triple therapy is newly investigated treatment modality, biomarker study plays important role on fine toning the diet and treatment morning. Funding: None