癫癇患者血清瓜氨酸水平升高临床意义

Clinical significance of elevated serum citrulline levels in patients with epilepsy

目的探讨癫癇患者血清瓜氨酸水平升高的临床意义,为临床提高抗癫癇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癇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,以明确癫癇病因诊断。结果共159例隐源性癫癇病例,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。经抗癫癇药物治疗至少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,抗癫癇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癇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,其抗癫癇药物疗效可能降低。

Objective To discuss the clinical significance of elevated serum citrulline levels inpatients with epilepsy, and to provide new idea for improving the curative effect of antiepileptic drugs（AEDs）.MethodsSelect 159 child and adolescent patients with cryptogenic epilepsy but without brainstructural 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, includingSLC25A13 gene and ASS1 gene, in part of those patients with a higher citrulline level, in order to identifythe etiology of epilepsy.ResultsAmong 159 patients, the citrulline levels of 18 cases were searched for1.53-3.61 times higher than normal, and no causative mutation or novel mutation of SLC25A13 gene andASS1 gene was found in 6 cases who were performed gene testing. AEDs were given to those 18 patientsfor 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）, theefficacy of AEDs in those 18 cases were significantly lower（Z = 1.759, P = 0.039）. There was no significantdifference between these 2 groups in basic features including sex, onset age, duration of seizure, seizuretype, seizure frequency and kind of AEDs.ConclusionsHigher citrulline level（1.53-3.61 times） maylead to a negative effect on the efficacy of AEDs of child and adolescent patients with cryptogenic epilepsyin this study.