The many faces of Glut1 deficiency syndrome

J Child Neurol. 2014 Mar;29(3):349-59. doi: 10.1177/0883073812471718. Epub 2013 Jan 22.


Glucose transporter protein type 1 deficiency syndrome is a metabolic disorder manifesting as cognitive impairment, acquired microcephaly, epilepsy, and/or movement disorder caused by mutations in the SLC2A1 gene. We describe a cohort of isolated and familial cases of glucose transporter protein type 1 deficiency syndrome, emphasizing seizure semiology, electroencephalographic (EEG) features, treatment response and mutation pathogenicity. SLC2A1 mutations were detected in 3 sporadic and 4 familial cases. In addition, mutations were identified in 9 clinically unaffected family members in 2 families. The phenotypic spectrum of glucose transporter protein type 1 deficiency is wider than previously recognized, with considerable intra-familial variation. Diagnosis requires either hypoglycorrachia followed by SLC2A1 sequencing or direct gene sequencing. A ketogenic diet should be the first line of treatment, but more flexible diets, like the Atkins modified diet, can also be followed. Carbonic anhydrase inhibitors, such as acetazolamide or zonisamide, can be effective for seizure control.

Keywords: SLC2A1 gene; carbonic anhydrase inhibitors; glucose transporter protein type 1 deficiency syndrome; ketogenic diet.

MeSH terms

  • Adolescent
  • Brain / physiopathology
  • Carbohydrate Metabolism, Inborn Errors / diagnosis
  • Carbohydrate Metabolism, Inborn Errors / genetics*
  • Carbohydrate Metabolism, Inborn Errors / physiopathology*
  • Carbohydrate Metabolism, Inborn Errors / therapy
  • Carbonic Anhydrase Inhibitors / therapeutic use
  • Child
  • Child, Preschool
  • Cohort Studies
  • DNA Mutational Analysis
  • Diagnosis, Differential
  • Diet, Ketogenic
  • Electroencephalography
  • Family
  • Glucose Transporter Type 1 / deficiency*
  • Glucose Transporter Type 1 / genetics
  • Humans
  • Monosaccharide Transport Proteins / deficiency*
  • Monosaccharide Transport Proteins / genetics
  • Mutation
  • Pedigree
  • Phenotype
  • Seizures / genetics
  • Seizures / physiopathology
  • Seizures / therapy
  • Young Adult


  • Carbonic Anhydrase Inhibitors
  • Glucose Transporter Type 1
  • Monosaccharide Transport Proteins
  • SLC2A1 protein, human

Supplementary concepts

  • Glut1 Deficiency Syndrome