Abstract：
Inborn errors of pyrimidine metabolism result from deficiencies in pyrimidine de novo synthesis, degradation, and salvage pathways. Enzymatic deficiencies in pyrimidine catabolism lead to mitochondrial neurogastrointestinal encephalopathy (MNGIE), pyrimidinuria, dihydropyrimidinuria, ureidopropionic aciduria, and other disorders. While MNGIE presents with gastrointestinal dysmotility, cachexia and leukoencephalopathy, pyrimidinuria, and dihydropyrimidinuria may show symptoms of epilepsy, autism, mental retardation, and dysmorphic features. The application of HPLC-MS/MS facilitates rapid screening of pyrimidine metabolites. Here we describe a sensitive and reliable LC-MS/MS method for quantitative determination of uracil, thymine, thymidine, dihydrouracil, and dihydrothymine in urine that are diagnostic biomarkers of MNGIE, pyrimidinuria, and dihydropyrimidinuria.
摘要：
嘧啶代谢的先天性错误是由于嘧啶从头合成的缺陷，降解，和救助途径。嘧啶分解代谢的酶缺乏导致线粒体神经胃肠脑病（MNGIE），嘧啶尿症,二氢嘧啶尿症,脲基丙酸尿症，和其他疾病。虽然MNGIE表现为胃肠动力障碍，恶病质和白质脑病,嘧啶尿症,二氢嘧啶尿症可能表现出癫痫的症状，自闭症,智力迟钝,和畸形特征。HPLC-MS/MS的应用有利于嘧啶代谢物的快速筛选。在这里，我们描述了一种灵敏可靠的LC-MS/MS方法，用于定量测定尿嘧啶，胸腺嘧啶,胸苷,二氢尿嘧啶,尿液中的二氢胸腺嘧啶是MNGIE的诊断生物标志物，嘧啶尿症,和二氢嘧啶尿症.
