Methylenetetrahydrofolate reductase (MTHFR) Deficiency in Epileptic Children

Abstract

Epilepsy (from the Ancient Greek verb meaning to seize, possess, or afflict) is a group of long-term neurological disorders characterized by epileptic seizures.The Methylenetetrahydrofolate reductase enzyme is the rate-limiting enzyme in the methyl cycle, and it is encoded by the MTHFR gene. Disturbed function of the enzyme results in hyperhomocysteinemia and causes severe vascular and neurological disorders and developmental delay. Methylenetetrahydrofolate (MTHFR) deficiency is an inborn error of metabolism where the manifestations are usually restricted to the nervous system at initial presentation. The present study was conducted in order to detect methylenetetrahydrofolate reductase enzyme and its relation to homocysteine, folic acid, vitamine B12, and AEDs serum levels in epileptic children. This study was a case-control study, was conducted on 80 epileptic children diagnosed with idiopathic epilepsy according to guidelines of The Classifications of the International League Against Epilepsy (ILAE) [1989], with age ranging from 2-16 years old. They were recruited from the Pediatric Neurology outpatients 'clinic of children’s Hospital, Ain Shams University. Patients were divided into 4 groups each group comprised of 20 patients: Group1 on Valproic acid, Group 2 on Carbamazepine, Group3 on new drug (Levetiracetam), and Group4 on polytherapy. All groups were studied before and after folic acid administration for 1 month. Twenty non epileptic children with the same age and sex as patients served as controls. All included patients were subjected to detailed medical& developmental history (age of onset, duration of seizures, Seizures (types & frequency) & Chalfont seizures scale, AEDs therapy, symptoms of neurological and other systems involvement. Clinical examination with stress on assessment of EEG and neurological examination. Routine workup as CBC, liver & kidney function tests. Serum levels of Homocysteine, Folic acid; Vit B12 and MTHFR were measured by Enzyme-Linked ImmunoSorbent Assay (ELISA). The mean serum levels of MTHFR enzyme and folic acid were significantly decreased in epileptic patients compared to healthy controls, while serum level of Homocysteine (Hcy) was significantly increased in epileptic patients compared to controls before folic acid supplementation. The mean serum level of Hcy was significantly increased while serum level of folic acid was significantly decreased in epileptic patients on polytherapy compared to those on monotherapy. Furthermore, the mean serum levels of MTHFR were significantly higher in epileptic patients receiving single new AEDs (levetiracetam) compared to patients on carbamazepine before folic acid supplemetation. Also folic acid serum levels were significantly higher in patients on levetiracetam than patients on single old AEDs (valproate or carbamazepine). While Hcy serum levels were significantly lower in patients on levetiracetam compared to those on single old AEDs. Homocysteine serum levels were significantly decreased, while serum levels of folic acid were significantly increased in both patients on monotherapy and polytherapy after folic acid supplementation. The mean serum MTHFR levels were significantly increased among epileptic patients receiving levetiracetam and valproic compared to those on carbamazepine after folic acid supplementation. Also folic acid levels were significantly increased in patients on levetiracetam compared to patients on single old AEDs (valproic acid or carbamazepine), while Hcy serum levels were significantly decreased in the same patients. Serum levels of MTHFR were increased in patients on monotherapy more significant in patients on valproic and significantly in patients on polytherapy after folic acid supplementation. A significant positive correlation was found between mean serum MTHFR levels and severity of convulsion before and after folic acid supplementation.