No abstract

The International League Against Epilepsy officially revised its classification in 2017, which amended “epileptic encephalopathy” to “developmental and epileptic encephalopathy”. With the development of genetic testing technology, an increasing number of genes that cause developmental and epileptic encephalopathies are being identified. Among these, solute transporter dysfunction is part of the etiology of developmental and epileptic encephalopathies. Solute carrier transporters play an essential physiological function in the human body, and their dysfunction is associated with various human diseases. Therefore, in-depth studies of developmental and epileptic encephalopathies caused by solute carrier transporter dysfunction can help develop new therapeutic modalities to facilitate the treatment of refractory epilepsy and improve patient prognosis. In this article, the concept of transporter protein disorders is first proposed, and nine developmental and epileptic encephalopathies caused by solute carrier transporter dysfunction are described in detail in terms of pathogenesis, clinical manifestations, ancillary tests, and precise treatment to provide ideas for the precise treatment of epilepsy.

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.