Abstract: Objective  To discuss the clinical significance of elevated serum citrulline levels in patients with epilepsy, and to provide new idea for improving the curative effect of antiepileptic drugs (AEDs).  Methods  Select 159 child and adolescent patients with cryptogenic epilepsy but without brain structural damage, screen serum concentration of citrulline in these patients by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and perform citrulline metabolism-related gene testing, including SLC25A13 gene and ASS1 gene, in part of those patients with a higher citrulline level, in order to identify the etiology of epilepsy.  Results  Among 159 patients, the citrulline levels of 18 cases were searched for 1.53-3.61 times higher than normal, and no causative mutation or novel mutation of SLC25A13 gene and ASS1 gene was found in 6 cases who were performed gene testing. AEDs were given to those 18 patients for at least one year. Seven cases (7/18) were free of clinical seizures, and 3 cases (3/18) had at least 75% reduction in seizure frequency, 3 cases (3/18) 50%-75% reduction in seizure frequency, 5 cases (5/18) seizure reduction below 50% . Compared with 30 cases with normal citrulline level (control group), the efficacy of AEDs in those 18 cases were significantly lower (Z = 1.759, P = 0.039). There was no significant difference between these 2 groups in basic features including sex, onset age, duration of seizure, seizure type, seizure frequency and kind of AEDs.  Conclusions  Higher citrulline level (1.53-3.61 times) may lead to a negative effect on the efficacy of AEDs of child and adolescent patients with cryptogenic epilepsy in this study.

Key words: Epilepsy, Citrullinemia, Anticonvulsants, Mass spectrometry

摘要： 目的 探讨癫痫患者血清瓜氨酸水平升高的临床意义，为临床提高抗癫痫药物疗效提供参考思路。方法 采用液相色谱-串联质谱法筛查无脑结构性损伤的儿童或青少年隐源性癫痫患者血清瓜氨酸水平，部分患者行瓜氨酸代谢相关基因SLC25A13 和ASS1 基因检测，以明确癫痫病因诊断。结果 共159 例隐源性癫痫病例，18 例血清瓜氨酸水平高于正常参考值上限1.53 ~ 3.61 倍，其中6 例行SLC25A13 和ASS1 基因检测，均未发现致病性突变或新突变。经抗癫痫药物治疗至少1 年，发作完全控制率为7/18、发作频率减少> 75%者占3/18、减少50% ~ 75%者占3/18、减少< 50%者占5/18，抗癫痫药物疗效较血清瓜氨酸水平正常患者降低（Z = 1.759，P = 0.039）。结论 儿童或青少年隐源性癫痫患者血清瓜氨酸水平升高至正常参考值上限1.53 ~ 3.61倍时，其抗癫痫药物疗效可能降低。

关键词: 癫痫, 瓜氨酸血症, 抗惊厥药, 质谱分析法