Metabolomic and Molecular Genetic Markers of Obesity-associated Epilepsy in Children

Background. Various epileptic syndromes can be comorbid with other pathologies, in particular, with excess weight. Research on the correlation between obesity and epilepsy in children is quite controversial. Identifying various metabolomic and molecular genetic markers of epilepsy is an extremely interesting task, which will allow the development of diagnostic algorithms for this pathological condition. The aim of the work is to identify the main metabolic and molecular genetic changes in epilepsy in children associated with obesity. Methods. The study included 24 patients aged from 1 year to 17 years: 16 patients with with epilepsy due to obesity and 8 patients of the control. The gender distribution was 15 girls and 9 boys. The study of the profile of 60 organic acids in urine was carried out by HPLC-MS. Targeted sequencing of mitochondrial dynamics genes (MFN1, MFN2, OPA1, DRP1) was performed using the NGS method. Results. In the case-group the upper reference limit of a number of markers of the Krebs cycle, mitochondrial dysfunction, bacterial dysbiosis and lactic acid levels were exceeded. Targeted NGS sequencing of four mitochondrial dynamics genes (MFN1, MFN2, OPA1, DRP1) of patients with epilepsy due to obesity and comparison group did not reveal pathological mutations in mitochondrial dynamics genes. However, 14 of the 16 patients with obesity-associated epilepsy were found to have the heterozygous OPA1 rs76426470 genetic variant (GA genotype), while all patients in the control group had the homozygous variant (GG genotype). Conclusion. Thus, we have identified a number of metabolic markers associated with epilepsy in children against the background of obesity.