The authors describe two sporadic children with pure and complex hereditary spastic paraplegia (HSP) without paroxysmal non-epileptic movement disorders harboring heterozygous de novo SLC2A1 pathogenic variants.
Future research should focus on subpopulations of focal epilepsy with lower age of seizure onset particularly with co-existent movement disorders in which GLUT1 mutations may play a more important role.
Dysfunction of the cerebral glucose transporter GLUT1 (encoded by SLC2A1) is known to result in epilepsy, intellectual disability (ID), and movement disorder.
No significant differences were found in terms of type of movement disorder, whilst Paroxysmal Exertion-induced Dyskinesia (PED) is confirmed to be the most characteristic movement disorder type in GLUT1DS.
Mutations in SLC2A1 were detected in 5 (10%) of 50 patients with absence epilepsy, and in one (2.7%) of 37 patient with unselected epilepsies, ID, and/or various movement disorders.
Familial paroxysmal exercise-induced dyskinesia (PED) is a rare movement disorder that is mostly caused by mutations in the solute carrier family 2, member 1 (SLC2A1) gene and inherited in an autosomal dominant manner.
A part from this classic phenotype, clinical conditions associated with a deficiency of GLUT1 are highly variable and several atypical variants have been described; in particular, patients with movement disorders, but without seizures, with paroxysmal exertion-induced dyskinesia, have been reported.
GLUT1-DS is characterized by movement disorders, including paroxysmal exercise-induced dystonia (PED), as well as seizures, mental retardation and hypoglycorrhachia.