Aktuelle Neurologie 2009; 36 - V79
DOI: 10.1055/s-0029-1238350

A GLUT1 mutation in patients with spastic paraplegia and paroxysmal dyskinesia

YG Weber 1, C Kamm 1, J Kempfle 1, A Suls 1, T Wuttke 1, A Salvo-Vargas 1, A Bellan-Koch 1, S Maljevic 1, T Gasser 1, P DeJonge 1, G Auburger 1, H Lerche 1
  • 1Ulm, Tübingen; Antwerpen, B; Frankfurt/Main

Glut1 is the glucose transporter of the blood brain barrier, thus a crucial molecule to deliver the most important energy carrier to the brain. Mutations in Glut1 have been found in Glut1-deficiency syndrome, a severe syndrome of early childhood with drug resistant epilepsy, microcephaly and progressive mental retardation. Recently, we detected mutations in Glut1 in patients with paroxysmal exercise-induced dyskinesia. Previously, Auburger and colleagues described a family with paroxysmal dyskinesia in combination with mild gait ataxia and constant spastic paraplegia in some patients (CSE, DYT9; Genomics 1996; 31:90–94). The family included 18 affected family members and 11 unaffected probands. Linkage had been found close to the Glut1 locus on chromosome 1p. We now re-analyzed the family clinically, recruited more family members, and sequenced the Glut1 gene SLC2A1. We found a p.R212C missense mutation. Functional analysis of the mutation expressed in Xenopus laevis oocytes revealed a significant reduction of glucose uptake compared to the wildtype. Western blots indicated a possibly slight reduction in protein stability, but surface expression was not altered in oocytes. Our findings indicate that constant spastic paraplegia may be part of the phenotype associated with Glut1 mutations, which appear to be more common than previously assumed. Since such patients can be treated successfully with a ketogenic diet, mutation screening should be performed in appropriate cases.