Diagnostic method for inborn errors of pyrimidine metabolism

2015 Fiscal Year Final Research Report

• Project/Area Number: 26860818
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Fujita Health University
• Principal Investigator: NAKAJIMA Yoko 藤田保健衛生大学, 医学部, 助教 (70598309)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: ピリミジン代謝異常症 / 尿中ピリミジン代謝物分析 / 5-フルオロウラシル / ハイリスクスクリーニング / UPLC-MS/MS / 遺伝子診断

Outline of Final Research Achievements

Inborn errors of pyrimidine degradation pathway have wide clinical aspects and show very severe side effects of 5-fluorouracil related anticancer drugs. However, the details of these diseases, such as disease frequency or genetic mutations are unclear, because the number of reported patients is limited.
In this study, we established the diagnostic system for inborn errors of pyrimidine degradation pathway by simultaneous analysis of urinary pyrimidine metabolites using UPLC-MS/MS followed by genetic analysis. The genetic analysis revealed that UPB1 R326Q mutation was identified in all patients with beta-ureidopropionase deficiency and 70% of these patients were homozygote of this mutation. Population study showed that 2% of healthy Japanese were carrier of the R326Q mutation. This result showed that beta-ureidopropionase deficiency is not as rare as generally considered in Japan.

Free Research Field

先天代謝異常症