Gene variations of glutamate metabolism pathway and epilepsy

Abstract

Background Epilepsy is a paroxysmal disorder of the brain, caused by an imbalance of neuronal excitation and inhibition. Glutamate is the most important excitatory neurotransmitter in the brain and plays an important role in epileptogenesis. Mutations in genes at any step/component of the glutamate metabolic pathway may lead to the development of epilepsy or epileptic encephalopathy. Methods Clinical history of 3 epilepsy patients with genetic variations of the glutamate metabolism pathway was collected. Electroencephalogram recording and magnetic resonance imaging were performed in each patient. We also reviewed recent literature for a variety of the genetic variations involved in epilepsy. Results Case 1 was a SLC1A2 mutation-carrier diagnosed with developmental and epileptic encephalopathy (DEE) 41, whose seizures decreased after start of the ketogenic diet. Case 2 carried a GRIN2A gene mutation and was seizure-free for three years after taking levetiracetam and vitamin B6. Case 3 was a GRIN2B mutation-carrier diagnosed with DEE 27, who seizures diminished after taking oxcarbazepine. Conclusions Preclinical and clinical evidence supports the therapeutic potential of glutamatergic signaling-targeting treatments for epilepsy. More studies are needed to discover novel DEE-related genetic mutations in the glutamate metabolic pathway.

Fundamental neurochemistry review: Glutamatergic dysfunction as a central mechanism underlying flavivirus‐induced neurological damage

“…Seizures are frequently reported in flavivirus‐infected patients, not only during the acute stages of infection but also late (months‐years) after disease resolution. It has been proposed that the identification of patients with mutations in glutamatergic system players may help identify the population at increased risk of epilepsy (Feng et al, 2022).…”

Movement Disorders in GRIA2‐Related Disorder – Expanding the Genetic Spectrum of Developmental Dyskinetic Encephalopathy

“…2 The GluR2 accounts for the majority of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR) in brain, thereby playing a vital role in the fastexcitatory glutamatergic transmission, synaptic communication and plasticity. 6,7 This subunit also regulates the Ca 2+ penetration and voltage rectification of AMPAR, causing abnormal excitation of the basal ganglia circuits. 8 These pathophysiological mechanisms may contribute to the various clinical manifestations described above.…”