In vitro evaluation of fatty acid oxidation capacity for accurate prognosis of fatty acid oxidation disorders

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K08300
• 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: Shimane University
• Principal Investigator: Yamada Kenji 島根大学, 医学部, 特別協力研究員 (70624930)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 脂肪酸代謝異常症 / VLCAD欠損症 / CPT2欠損症 / IVPアッセイ / グルタル酸血症2型

Outline of Final Research Achievements

Fatty acid oxidation disorders can lead to sudden death triggered by starvation and high fever, but many patients with milder form remain asymptomatic. This study aims to differentiate between severe and milder forms by in vitro analysis using fibroblasts obtained from patients, in order to determine therapeutic plan and management based on the severity of the disease. Changing conditions of cell culture, such as culture temperature and substrate type/concentration, and using various methods to assess fatty acid oxidation capacity, such as ATP levels of culture medium and in vitro prove assay, could partially distinguish between the severe and milder forms. However, it was challenging to completely distinguish between severe and milder forms. On the other hand, it was found that culture temperature and various drugs/substrates could affect fatty acid oxidation capacity, suggesting the potential for predicting milder form through their application.

Free Research Field

先天代謝異常症

Academic Significance and Societal Importance of the Research Achievements

脂肪酸代謝異常症は非常に稀な疾患ではあるが、新生児スクリーニングで発症前診断されるケースが多い。一回の急性発作で死に至る事もあることから、乳幼児期には発熱したら入院するといった厳重な管理が行われている。しかしながら、生涯にわたって発症しないような軽症例も多く見つかっている。本研究結果からは、発症前に病気の重症度を正確に予測することは難しく、軽症が予想される症例であっても厳重な管理を行わざるを得ないことが分かった。
一方、患者由来細胞を使った実験系である程度の予後予測が出来ることから、一部の患者については重症度に見合った管理を提供できる可能性はあり、これは患者QOL向上や医療費抑制に寄与する。