The expanding phenotype of GLUT1-deficiency syndrome

Brain Dev. 2009 Aug;31(7):545-52. doi: 10.1016/j.braindev.2009.02.008. Epub 2009 Mar 21.


Transport of glucose from the bloodstream across the blood-brain barrier to the central nervous system is facilitated by glucose transport protein type 1 (GLUT1), the first member of the solute carrier family 2 (SLC2). Heterozygous mutations in the GLUT1/SLC2A1 gene, occurring de novo or inherited as an autosomal dominant trait, result in cerebral energy failure and a clinical condition termed GLUT1-deficiency syndrome (GLUT1-DS). Clinical features usually comprise motor and mental developmental delay, seizures with infantile onset, deceleration of head growth often resulting in acquired microcephaly, and a movement disorder with ataxia, dystonia, and spasticity. Subsequent to the delineation of this classic phenotype the variability of signs and symptoms in GLUT1-DS is being recognized. Patients with (i) carbohydrate-responsive symptoms, with (ii) predominant ataxia or dystonia, but without seizures, and with (iii) paroxysmal exertion-induced dyskinesia and seizures have been reported. Common laboratory hallmark in all phenotypes is the reduced glucose level in cerebrospinal fluid with lowered CSF-to-blood glucose ratio. Treatment with a ketogenic diet results in marked improvement of seizures and movement disorders.

Publication types

  • Review

MeSH terms

  • Brain / pathology
  • Brain / physiopathology
  • Diet, Ketogenic
  • Dyskinesias / cerebrospinal fluid
  • Dyskinesias / genetics
  • Dyskinesias / pathology
  • Epilepsy / cerebrospinal fluid
  • Epilepsy / genetics
  • Epilepsy / pathology
  • Exercise
  • Glucose / cerebrospinal fluid
  • Glucose / metabolism
  • Glucose Metabolism Disorders / cerebrospinal fluid
  • Glucose Metabolism Disorders / genetics*
  • Glucose Metabolism Disorders / metabolism
  • Glucose Metabolism Disorders / pathology
  • Glucose Transporter Type 1 / deficiency*
  • Glucose Transporter Type 1 / genetics*
  • Humans
  • Movement Disorders / cerebrospinal fluid
  • Movement Disorders / genetics
  • Movement Disorders / pathology
  • Mutation
  • Phenotype
  • Syndrome
  • Video Recording


  • Glucose Transporter Type 1
  • SLC2A1 protein, human
  • Glucose