Glucose transporter type I deficiency and other glucose flux disorders

Research output: Chapter in Book/Report/Conference proceedingChapter


Most (but not all) patients with glucose transporter (GLUT) type I deficiency (G1D) are haploinsufficient in SLC2A1, the gene that encodes the GLUT isoforms present in red blood cells, endothelial cells of the blood-brain barrier, and astrocytes. G1D is expected, on biochemical principles, to result in decreased blood to brain (i.e., either plasma to brain or, virtually, red blood cell to brain) and intracerebral glucose flux and, in mice, this is associated with diminished cerebral acetyl-coenzyme A contents. Thus G1D probably stems from depletion (or perhaps from the detrimental consequences of repletion) of energetic precursors centrally situated with respect to cerebral metabolism. However, it is unknown how this impacts other aspects of brain development and even postdevelopment brain function since there are seemingly refractory aspects of the disorder after metabolic treatment. Paradoxically, G1D is not associated with global neural hypoexcitability as a result of diminished glucose influx, but with focal hyperexcitability: Spike-wave epilepsy and paroxysmal dyskinesia constitute the best defined G1D syndromes, but as many as 1% of idiopathic generalized epilepsies are probably caused by G1D. Many patients also exhibit dystonia, ataxia, and dysarthria, either in isolation or in conjunction with other nonmotor manifestations such as intellectual disability and microcephaly. A modified Atkins diet or a ketogenic diet has proved effective in controlling seizures but has had little measurable effect on the associated cognitive impairment and behavioral disturbances. As with all neurometabolic disorders, it is important to expand our understanding of disease mechanisms (whether reversible or potentially irreversible) if more effective treatments are to be developed.

Original languageEnglish (US)
Title of host publicationRosenberg’s Molecular and Genetic Basis of Neurological and Psychiatric Disease
Subtitle of host publicationVolume 1
Number of pages15
ISBN (Electronic)9780128139554
StatePublished - Jan 1 2020
Externally publishedYes


  • Absence
  • Astrocyte
  • Ataxia
  • Blood-brain barrier
  • Chorea
  • Dyskinesia
  • Dystonia
  • Epilepsy
  • G1D
  • GABA
  • Glut1
  • Glut1 deficiency
  • Glutamate
  • Hemolysis
  • Ketogenic diet
  • Modified atkins diet
  • Spasticity
  • Spike-wave
  • Synapse
  • Thalamocortical

ASJC Scopus subject areas

  • Medicine(all)


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