Molecular analysis and anticonvulsant therapy in two patients with glucose transporter 1 deficiency syndrome: a successful use of zonisamide for controlling the seizures.
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.
Takahashi
Satoru
S
Department of Pediatrics, Asahikawa Medical College, 2-1-1-1 Midorigaoka-Higashi, Asahikawa, Hokkaido 078-8510, Japan. satoru5p@asahikawa-med.ac.jp
Ohinata
Junko
J
Suzuki
Nao
N
Amamiya
Satoshi
S
Kajihama
Aya
A
Sugai
Rika
R
Araki
Akiko
A
Fujieda
Kenji
K
Tanaka
Hajime
H
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
D000927:Anticonvulsants; D051272:Glucose Transporter Type 1; D007555:Isoxazoles; D008756:Methylgalactosides; C031552:methyl beta-galactoside; D000078305:Zonisamide; D005947:Glucose