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Table 1 Genetic variations in the pathway of glutamate metabolism and related phenotypes

From: Gene variations of glutamate metabolism pathway and epilepsy

Pathway

Gene name

Phenotype

Inheritance

Treatment

Prognosis

Glutamate synthesis

GLS

DEE71, DD, ataxia

AR, AD

Unknown

DRE, DD

GLUD1

Hyperinsulinism-hyperammonemia syndrome

AD

diazoxide, ASM (LEV, ZNS)

DRE, DD

Glutamate transport

SLC1A2

DEE41

AD

EAAT2 translation, ketogenic diet

Unknown

EAAT1, 3, 4, 5

    

Glutamate receptors

GRIN1

Neurodevelopmental disorder with or without hyperkinetic movements and seizures

AD, AR

ASM (VGB, VPA, TPM, LEV, CBZ, CZP)

DRE, DD

GRIN2A

Focal epilepsy with speech disorder, intellectual disability 

AD

MAT, ASM (TPM, CBZ, FBM, LEV)

DRE, DD

GRIN2B

DEE27, intellectual disability 

AD

MAT, OXC

DRE, DD

GRIN2D

DEE46

AD

MAT, intravenous immunoglobulin, oral steroids, and magnesium

DRE, DD

GRIA2

Neurodevelopmental disorder with language impairment and behavioral abnormalities

AD

AMPA receptor inhibitors (perampanel)

Unknown

GRIA4

Neurodevelopmental disorder with or without seizures and gait abnormalities

AD

Unknown

Unknown

GRM7

Neurodevelopmental disorder with seizures, hypotonia, and brain abnormalities

AR

PAM

DRE, DD

Glutamate metabolism

GLUL

Glutamine deficiency

AR

Glutamine

Effective drug control

  1. Abbreviations: ASM antiseizure medications, AR autosomal recessive, AD autosomal dominant, CBZ carbamazepine, CZP clonazepam, CBZ carbamazepine, DD developmental delay, DRE medically refractory epilepsy, DEE developmental epileptic encephalopathy, EAATs excitatory amino acid transporters, FBM felbamate, KA kainite, LEV levetiracetam, MAT memantine, OXC oxcarbazepine, PAM positive allosteric modulator, TPM Topamax, VPA valproic acid, VGB vigabatrin, ZNS zonisamide