2.A.29.14.3
Mitochondrial glutamate carrier 1 (GC1); glutamate:H⁺ symporter 1 (SLC25A22). It plays a role in glucose-stimulated insulin secretion by β-cells (Casimir et al., 2009), and is responsible for migrating partial seizures in neonatal infancy (MPSI), a severe condition with few known etiologies (Poduri et al. 2013). Early infantile epileptic encephalopathy (EIEE) is a heterogeneous group of severe forms of age-related developmental and epileptic encephalopathies with onset during the first weeks or months of life. EIEE type 3 is caused by variants affecting the function of SLC25A22, which is also responsible for epilepsy of infancy with migrating focal seizures (EIMFS). Lemattre et al. 2019 reported a family with a less severe phenotype of EIEE type 3. Functional studies showed that glutamate oxidation was defective. There are three groups according to the severity of the SLC25A22-related disorders. The variants were classified according to the location of the mutation, depending on the protein domain; patients with two variants located in helical transmembrane domains presented a severe phenotype, whereas patients with at least one variant outside helical transmembrane domains presented a milder phenotype. Thus, there seems to be a continuum of disorders related to SLC25A22 (Lemattre et al. 2019).