Comprehensive laboratory assessment of energy metabolism disorders in children with epilepsy: diagnostic significance of lactate/pyruvate and 3-hydroxybutyrate/acetate ratios

Relevance. Early-onset epilepsy in children is often a clinical manifestation of neuronal energy metabolism disorders, including mitochondrial dysfunction, pyruvate metabolism defects, and fatty acid β-oxidation. However, standard clinical and instrumental diagnostic methods do not always allow for the early identification of the metabolic nature of the disease. Objective. To substantiate a laboratory approach to the early diagnosis of metabolically mediated epilepsy in children based on the comprehensive determination of lactate, pyruvate, acetoacetate, and 3-hydroxybutyrate, with calculation of diagnostically significant ratios. Material and methods. The study included 54 children with seizure disorder and 80 apparently healthy children, matched for age and gender. Lactate, pyruvate, 3-hydroxybutyrate, and acetoacetate were determined using enzymatic spectrophotometric methods in deproteinized blood samples in accordance with the recommendations of specialized laboratory guidelines. Reference intervals and interpretation thresholds were formed based on data from pediatric test catalogs (Mayo Clinic Laboratories, Children’s Minnesota, CHOP, Canterbury Health Laboratories, Newcastle NHS) and verified using CALIPER principles. Results. Comparative analysis of energy metabolism parameters revealed a statistically significant increase in the lactate/pyruvate (L/P) ratio in children with seizure disorder compared to the control group (p<0.001), with a partial overlap of absolute lactate values with reference intervals. ROC analysis demonstrated high diagnostic performance of the L/P ratio (AUC=0.84; 95% CI 0.77—0.90) with an optimal cutoff value of ≥14.5, which is consistent with data from specialized laboratory and clinical studies. Conclusion. Comprehensive laboratory assessment of energy metabolism parameters with calculation of lactate/pyruvate and 3-hydroxybutyrate/acetoacetate ratios is a valid and clinically significant approach to the early diagnosis of metabolically induced epilepsy in children and can be recommended for implementation in clinical diagnostic laboratories.