Department of Pharmacy, Faculty of Medicine, University of Prishtina, Prishtina 10000, Kosovo.
Institute of Pharmacology and Toxicology, Faculty of Medicine, University of Prishtina, Prishtina 10000, Kosovo.
Int J Mol Sci. 2018 Jan 5;19(1):122. doi: 10.3390/ijms19010122.
Monogenic and polygenic mutations are important contributors in patients suffering from epilepsy, including metabolic epilepsies which are inborn errors of metabolism with a good respond to specific dietetic treatments. Heterozygous variation in solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1) and mutations of the GLUT1/SLC2A2 gene results in the failure of glucose transport, which is related with a glucose type-1 transporter (GLUT1) deficiency syndrome (GLUT1DS). GLUT1 deficiency syndrome is a treatable disorder of glucose transport into the brain caused by a variety of mutations in the SLC2A1 gene which are the cause of different neurological disorders also with different types of epilepsy and related clinical phenotypes. Since patients continue to experience seizures due to a pharmacoresistance, an early clinical diagnosis associated with specific genetic testing in SLC2A1 pathogenic variants in clinical phenotypes could predict pure drug response and might improve safety and efficacy of treatment with the initiation of an alternative energy source including ketogenic or analog diets in such patients providing individualized strategy approaches.
单基因和多基因突变是癫痫患者的重要致病因素,包括代谢性癫痫,这是一种先天性代谢错误,对特定的饮食治疗有很好的反应。溶质载体家族 2,易化葡萄糖转运蛋白成员 1(SLC2A1)的杂合变异和 GLUT1/SLC2A2 基因突变导致葡萄糖转运失败,与葡萄糖 1 型转运体(GLUT1)缺乏综合征(GLUT1DS)有关。GLUT1 缺乏综合征是一种可治疗的脑葡萄糖转运障碍,由 SLC2A1 基因的多种突变引起,这些突变导致不同的神经发育障碍,也伴有不同类型的癫痫和相关的临床表型。由于患者继续因药物耐药而出现癫痫发作,因此在临床表型中对 SLC2A1 致病性变异进行特定的基因检测与早期临床诊断相关,可以预测纯药物反应,并可能通过在这些患者中启动替代能源(包括生酮或类似饮食)来提高治疗的安全性和疗效,从而提供个体化的策略方法。