Evaluating the suitability of 6-oxo-PIP as a novel biomarker for pyridoxine-dependent epilepsy in multiple samples

Objective To evaluate the suitability of 6-oxo-PIP as a possible new biomarker for PDE-ALDH7A1, and to compare it with α-AASA-P6C, PA, and α-AAA. Methods The biomarkers of 12 PDE-ALDH7A1 patients and age-matched epilepsy control patients were quantitatively assayed by LC-MS/MS. Four types of samples were prepared, including plasma, dried blood spots (DBS), urine, and dried urine spots (DUS). Results In PDE-ALDH7A1 group, the values of α-AASA-P6C and 6-oxo-PIP were above the reference range, while α-AAA and PA could be normal or slightly elevated. The concentration ranges of PA and α-AAA overlapped partially between PDE-ALDH7A1 group and epilepsy group in all specimens, while α-AASA-P6C and 6-oxo-PIP did not overlap between the two groups. A positive correlation between plasma and DBS, or urine and DUS of 6-oxo-PIP was found, and the level of 6-oxo-PIP in urine and DUS was much higher than other types of samples. Although the values of α-AASA-P6C was positively correlated in plasma and DBS or urine and DUS, the difference between plasma and DBS was significant. The concentrations of PA and α-AAA were positively correlated only in plasma and DBS or urine and DUS, respectively. Regardless of storage temperature, the concentrations of 6-oxo-PIP were above 95% of the initial value after 28 days in all specimens. Conclusions In PDE-ALDH7A1, 6-oxo-PIP was specific when compared with other epilepsy patients even under pyridoxine treatment. 6-oxo-PIP could be prepared into DUS for detection, making it possible for non-invasive screening of PDE. Regardless of sample type, 6-oxo-PIP is relatively stable at RT.