Advanced Neuroprotective Systems, Ltd., Kaplan's Medical Center Pediatric Department, Rehovot, Israel.
Med Hypotheses. 2012 Aug;79(2):157-64. doi: 10.1016/j.mehy.2012.04.022. Epub 2012 May 29.
The study testifies an assumption on epilepsy as an inborn error of pyridoxine metabolism and suggests non-invasive quantitative biomarkers for clarified evaluation of clinical status and monitoring an individual treatment by antiepileptic drugs. Urinary parameters of pyridoxal-phosphate (PLP)-dependent tryptophan degradation and the level of 4-pyridoxic acid, the end product of pyridoxine metabolism, were measured by HPLC method with simultaneous ultraviolet and fluorimetric detection in children with different forms of epilepsy and matched healthy controls. The concentrations of compounds formed or metabolized in the course of tryptophan degradation (kynurenines, indoxyl-sulfate) along with correlations between them turned out to be quantitative biomarkers useful for both clarifying patient's clinical state and monitoring antiepileptic treatment. In particular, the value of the ratio of 4-pyridoxic acid to kynurenine appears to be an index of an experienced seizure attack, while the ratio of 3-hydroxyanthranilic acid to 3-hydroxykynurenine reflects activity of kynureninase, the enzyme of critical sensitivity to PLP supply. Growing progressively worse, epilepsy is accompanied by aggravation of PLP-dependent disturbances of tryptophan metabolism and expanding inhibition of kynureninase. The affected pyridoxine metabolism is discussed as an inborn genetic trait in epilepsy in general, rather than a specific sign of pyridoxine-dependent epilepsy solely.
这项研究证明了癫痫是一种吡哆醇代谢的先天性错误的假设，并提出了非侵入性的定量生物标志物，用于明确评估临床状况和监测抗癫痫药物的个体治疗。通过 HPLC 方法，同时进行紫外和荧光检测，测量了儿童不同形式癫痫和匹配的健康对照组中依赖吡哆醛-5-磷酸（PLP）的色氨酸降解的尿参数和吡哆醇代谢的终产物 4-吡啶羧酸的水平。在色氨酸降解过程中形成或代谢的化合物的浓度（犬尿氨酸、吲哚硫酸酯）及其之间的相关性被证明是有用的定量生物标志物，可用于明确患者的临床状况和监测抗癫痫治疗。特别是，4-吡啶羧酸与犬尿氨酸的比值似乎是经历癫痫发作攻击的指标，而 3-羟基邻氨基苯甲酸与 3-羟基犬尿氨酸的比值反映了犬尿氨酸酶的活性，犬尿氨酸酶对 PLP 供应的敏感性是关键。随着病情的逐渐恶化，癫痫会伴随着 PLP 依赖性色氨酸代谢紊乱的加重和犬尿氨酸酶抑制的扩大。受影响的吡哆醇代谢被讨论为一般癫痫中的一种先天性遗传特征，而不仅仅是吡哆醇依赖性癫痫的特定标志。
