Biomaker analysis and exploration for early diagnosis of vitamin B6-dependent epilepsies

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07798
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Okayama University
• Principal Investigator: Akiyama Tomoyuki 岡山大学, 医歯薬学域, 准教授 (10379737)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ビタミンB6依存性てんかん / バイオマーカー / 遺伝子解析 / 酵素活性測定

Outline of Final Research Achievements

In order to establish an early diagnosis system for VB6-dependent epilepsies, we attempted to add measurable diagnostic biomarkers, improve genetic/enzyme diagnosis methods, and search for biomarkers for PLPBP deficiency, for which no biomarker has yet been discovered.
As a result, we expanded the existing VB6 measurement system and were able to almost determine the analysis conditions. It is currently undergoing validation. The analytical conditions for the biomarker of ALDH7A1 deficiency have been established. We were able to set up a system for genetic diagnosis. Regarding enzyme activity assays, the measurement conditions for ALDH7A1 protein have almost been determined. Clinical specimens from patients with PLPBP deficiency are currently being collected for metabolome analysis.

Free Research Field

小児神経学

Academic Significance and Societal Importance of the Research Achievements

VB6測定系の拡張とALDH7A1欠損症の新規バイオマーカーの測定条件が整ったため、本邦では今まで行えなかったPNPO欠損症の生化学診断や、ALDH7A1欠損症のより正確な生化学診断への糸口がつかめた。また、ALDH7A欠損症に関しては、遺伝子バリアントの機能解析体制の準備が進んだ。これらの成果によりVB6依存性てんかんの早期診断が可能になれば、早期治療による発作・発達予後の改善が期待され、患者のQOL向上が見込まれる。