Glut1 deficiency: when to suspect and how to diagnose?

Eur J Paediatr Neurol. 2012 Jan;16(1):3-9. doi: 10.1016/j.ejpn.2011.09.005. Epub 2011 Oct 1.

Abstract

Impaired glucose transport across the blood-brain barrier results in GLUT1 deficiency syndrome (GLUT1-DS), characterized by infantile seizures, developmental delay, acquired microcephaly, spasticity, ataxia, and hypoglycorrhachia. A part from this classic phenotype, clinical conditions associated with a deficiency of GLUT1 are highly variable and several atypical variants have been described; in particular, patients with movement disorders, but without seizures, with paroxysmal exertion-induced dyskinesia, have been reported. Most patients carry heterozygous de novo mutations in the GLUT1-gene but autosomal dominant and recessive transmission has been identified. Diagnosis is based on low cerebrospinal fluid glucose, in the absence of hypoglycemia, and it is confirmed by molecular analysis of the GLUT1-gene and by glucose uptake studies and immunoreactivity in human erythrocytes. Treatment with a ketogenic diet results in marked improvement of seizures and movement disorders. This review summarizes recent advances in understanding of GLUT1-DS and highlights the diagnostic and therapeutic approach to GLUT1-DS.

Publication types

  • Review

MeSH terms

  • Brain Diseases, Metabolic / diagnosis
  • Brain Diseases, Metabolic / genetics
  • Developmental Disabilities / diagnosis
  • Developmental Disabilities / genetics
  • Epilepsy / diagnosis
  • Epilepsy / genetics
  • Genetic Variation / genetics
  • Glucose Transporter Type 1 / deficiency*
  • Glucose Transporter Type 1 / genetics*
  • Humans

Substances

  • Glucose Transporter Type 1
  • SLC2A1 protein, human