Facilitated glucose transporter protein type 1 (GLUT1) deficiency syndrome: impaired glucose transport into brain-- a review

Eur J Pediatr. 2002 Jun;161(6):295-304. doi: 10.1007/s00431-002-0939-3. Epub 2002 Apr 16.

Abstract

Facilitated glucose transporter protein type 1 (GLUT1) deficiency syndrome (MIM 138140) defines a prototype of a novel group of disorders resulting from impaired glucose transport across blood-tissue barriers. It is caused by a defect in glucose transport into brain, mediated by the facilitative glucose transporter GLUT1. Since 1991, more than 70 patients have been identified. The hallmark of the disease is a low glucose concentration in the CSF (hypoglycorrhachia) in the presence of normoglycaemia (CSF/blood glucose ratio <0.4). Clinical features are variable and include seizures, developmental delay, acquired microcephaly, hypotonia, and a complex motor disorder with elements of ataxia, dystonia, and spasticity. The GLUT1 defect can be confirmed in erythrocytes by glucose uptake studies and GLUT1 immunoreactivity, and by molecular analysis of the GLUT1 gene. Several heterozygous mutations resulting in GLUT1 haploinsufficiency have been identified. An effective treatment is available by means of a ketogenic diet as ketone bodies serve as an alternative fuel for the developing brain.

Conclusion: this treatable condition should be suspected in children with unexplained neurological disorders associated with epilepsy and developmental delay and confirmed by a lumbar puncture.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Blood-Brain Barrier
  • Brain / metabolism*
  • Carbohydrate Metabolism, Inborn Errors / blood
  • Carbohydrate Metabolism, Inborn Errors / cerebrospinal fluid
  • Carbohydrate Metabolism, Inborn Errors / diagnosis*
  • Child, Preschool
  • Glucose / cerebrospinal fluid
  • Glucose / metabolism*
  • Glucose Transporter Type 1
  • Humans
  • Monosaccharide Transport Proteins / antagonists & inhibitors
  • Monosaccharide Transport Proteins / deficiency*
  • Monosaccharide Transport Proteins / genetics
  • Mutation
  • Syndrome

Substances

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