NMR-based metabolomics in pediatric drug resistant epilepsy – preliminary results

Abstract

Epilepsy in children is the most frequent, heterogeneous and difficult to classify chronic neurologic condition with the etiology found in 35–40% of patients. Our aim is to detect the metabolic differences between the epileptic children and the children with no neurological abnormalities in order to define the metabolic background for therapy monitoring. The studied group included 28 epilepsy patients (median age 12 months) examined with a diagnostic protocol including EEG, videoEEG, 24-hour-EEG, tests for inborn errors of metabolism, chromosomal analysis and molecular study. The reference group consisted of 20 patients (median age 20 months) with no neurological symptoms, no development delay nor chronic diseases. 1H-NMR serum spectra were acquired on 400 MHz spectrometer and analyzed using multivariate and univariate approach with the application of correction for age variation. The epilepsy group was characterized by increased levels of serum N-acetyl-glycoproteins, lactate, creatine, glycine and lipids, whereas the levels of citrate were decreased as compared to the reference group. Choline, lactate, formate and dimethylsulfone were significantly correlated with age. NMR-based metabolomics could provide information on the dynamic metabolic processes in drug-resistant epilepsy yielding not only disease-specific biomarkers but also profound insights into the disease course, treatment effects or drug toxicity.

The First Metabolome Analysis in Children with Epilepsy and ALG13-CDG Resulting from c.320A>G Variant

“…Figure 1 shows the 1H-NMR CPMG spectra of the serum samples obtained from three ALG13-CDG patients. The NMR spectra of the EG and RG groups are available in [ 15 ].…”

“…The age-dependency was determined from the carnitine relative intensities measured for RG, and the correction was made using the residual method for RG, EG, and ALG13 c.320A>G carriers. The detailed procedure for the age correction is described in detail in [ 15 ].…”

“…The mammalian glycome consists of up to several thousand glycan structures and may be larger even than the proteome. Aberrations in the glycosylation anabolic and catabolic mechanisms may disturb cell adhesion, cell signaling, and endocytosis, with congenital disorders of glycosylation (CDGs) affecting the central and peripheral nervous system, the endocrine system, and coagulation [ 15 , 16 , 19 , 20 ]. The metabolic effects of such aberrations can be monitored using NMR-based metabolomics.…”

“…The obtained metabolic profiles were then compared with the ones from the pediatric drug-resistant epilepsy patients (EG) as well as from the pediatric reference group (RG). The characteristics of the EG and RG groups and the detailed description of the blood samples collection, as well as the NMR acquisition protocol, are described in [ 15 ], and a brief summary is given below.…”

Oxidative Stress, a Crossroad Between Rare Diseases and Neurodegeneration

“…Although oxidative stress is not the primary cause of DS, the available evidence strongly indicates that oxidative stress and neuroinflammation are involved in the pathology pediatric epilepsy, mainly in the ensuing encephalopathy and deterioration of cognitive capabilities. Nuclear Metabolic Resonance (NMR) metabolomic analysis of pediatric drug-resistant epilepsies revealed changes in lactate, creatine, citrate, and lipids consistent with an increase in oxidative stress [192]. Regarding DS, GABAergic neurons differentiated from patient-derived iPSCs displayed a defective response to oxidative stress [193].…”