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.
Glucose transporter type 1 deficiency syndrome (Glut-1DS) is caused by autosomal dominant haplodeficiency or autosomal recessive with homozygous mutation of the glucose transporter 1 (SLC2A1) gene and is characterized by severe seizures, developmental delay, ataxia and acquired microcephaly.
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.
Our purpose is (1) to describe epilepsy phenotypes in a large Glut 1 DS cohort, to facilitate diagnosis; and (2) to describe cases in which non-KD agents achieved seizure freedom (SF), highlighting potential adjunctive treatments.
We analyzed the SLC2A1 gene in 12 Japanese Glut1-DS patients who were diagnosed by characteristic clinical symptoms and hypoglycorrhachia as follows: all patients had infantile-onset seizures and mild to severe developmental delay, and ataxia was detected in 11 patients.
In 2002, we identified a heterozygous missense mutation substituting glycine at residue 75 for tryptophan in a 10-year-old girl with intractable seizures and low glucose concentrations in the cerebrospinal fluid indicative of GLUT1 deficiency.