title: Molecular analysis and anticonvulsant therapy in two patients with glucose transporter 1 deficiency syndrome: a successful use of zonisamide for controlling the seizures.
abstract: Glucose transporter 1 (GLUT1) deficiency syndrome is caused by a deficit in glucose transport to the brain during the pre- and postnatal periods. Here, we report two cases of GLUT1 deficiency syndrome diagnosed on the basis of clinical features, reduced GLUT1 activities, and mutations in the GLUT1 gene. Patient 1 had a novel heterozygous 1bp insertion in exon 7 that resulted in a shift of the reading frame and the introduction of a premature stop codon at amino acid position 380. His clinical phenotype appeared to be more severe than that of Patient 2 who had a missense mutation in exon 8 resulting in an arginine-to-tryptophan substitution at amino acid position 333. Patient 1 had no meaningful words and could not walk unassisted, while Patient 2 could speak and walk unassisted. Both the patients developed seizures of various types that have been successfully treated with zonisamide. Although several antiepileptic drugs, including barbiturates, diazepam, chloralhydrate, and valproic acid, have been shown to inhibit GLUT1 function, the present study demonstrated no inhibitory effect of zonisamide on GLUT1-mediated glucose transport. Our data suggested that zonisamide might be preferable if add-on anticonvulsant therapy is required to control the seizures in patients with this disorder.
authors.affiliation: Department of Pediatrics, Asahikawa Medical College, 2-1-1-1 Midorigaoka-Higashi, Asahikawa, Hokkaido 078-8510, Japan. satoru5p@asahikawa-med.ac.jp
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.forename: Junko
authors.initials: J
authors.lastname: Ohinata
authors.forename: Nao
authors.initials: N
authors.lastname: Suzuki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Amamiya
authors.forename: Aya
authors.initials: A
authors.lastname: Kajihama
authors.forename: Rika
authors.initials: R
authors.lastname: Sugai
authors.forename: Akiko
authors.initials: A
authors.lastname: Araki
authors.forename: Kenji
authors.initials: K
authors.lastname: Fujieda
authors.forename: Hajime
authors.initials: H
authors.lastname: Tanaka
mesh_terms: D000927:Anticonvulsants / Q000627:therapeutic use*; D001692:Biological Transport / Q000187:drug effects; D002648:Child; D004252:DNA Mutational Analysis; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000172:deficiency*; D006801:Humans; D007555:Isoxazoles / Q000627:therapeutic use*; D008297:Male; D008756:Methylgalactosides / Q000378:metabolism; D012640:Seizures / Q000188:drug therapy* / Q000235:genetics*; D000078305:Zonisamide
chemical_list: D000927:Anticonvulsants; D051272:Glucose Transporter Type 1; D007555:Isoxazoles; D008756:Methylgalactosides; C031552:methyl beta-galactoside; D000078305:Zonisamide; D005947:Glucose