Autosomal dominant Glut-1 deficiency syndrome and familial epilepsy

Knut Brockmann, Dong Wang, Christoph G. Korenke, Arpad Von Moers, Yuan Yuan Ho, Juan M. Pascual, Kunyan Kuang, Hong Yang, Ma Li, Pamela Kranz-Eble, Jorge Fischbarg, Folker Hanefeld, Darryl C. De Vivo

Research output: Contribution to journalArticlepeer-review

133 Scopus citations


Glut-1 deficiency syndrome was first described in 1991 as a sporadic clinical condition, later shown to be the result of haploinsufficiency. We now report a family with Glut-1 deficiency syndrome affecting 5 members over 3 generations. The syndrome behaves as an autosomal dominant condition. Affected family members manifested mild to severe seizures, developmental delay, ataxia, hypoglycorrhachia, and decreased erythrocyte 3-O-methyl-D-glucose uptake. Seizure frequency and severity were aggravated by fasting, and responded to a carbohydrate load. Glut-1 immunoreactivity in erythrocyte membranes was normal. A heterozygous R126H missense mutation was identified in the 3 patients available for testing, 2 brothers (Generation 3) and their mother (Generation 2). The sister and her father were clinically and genotypically normal. In vitro mutagenesis studies in Xenopus laevis oocytes demonstrated significant decreases in the transport of 3-O-methyl-D-glucose and dehydroascorbic acid. Xenopus oocyte membranes expressed high amounts of the R126H mutant Glut-1. Kinetic analysis indicated that replacement of arginine-126 by histidine in the mutant Glut-1 resulted in a lower Vmax. These studies demonstrate the pathogenicity of the R126H missense mutation and transmission of Glut-1 deficiency syndrome as an autosomal dominant trait.

Original languageEnglish (US)
Pages (from-to)476-485
Number of pages10
JournalAnnals of Neurology
Issue number4
StatePublished - 2001

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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