Glucose transporter type 1 deficiency due to SLC2A1 gene mutations--a rare but treatable cause of metabolic epilepsy and extrapyramidal movement disorder; own experience and literature review

Dev Period Med. 2015 Oct-Dec;19(4):454-63.

Abstract

The aim: To present the molecular and clinical characteristics of three children with glucose deficiency syndrome, an inborn rare metabolic disease, caused by mutations in the SLC2A1 gene.

Material and methods: The investigation was carried out in three children: two girls and one boy showing symptoms of GLUT1 deficiency syndrome (GLUT1-DS). They were referred for SLC2A1 gene analysis.

Results: The presence of mutations in all of them was confirmed. Only point mutations were identified, two missenses p.Gly132Ser, p.Arg212Cys and amino acid insertion p.Ser_Val227insValProPro. In two cases the mutations arose de novo, one was heritable of paternal origin.

Conclusions: GLUT1-DS shows high clinical variability. It should be suspected in children of any age presenting with single features or a combination of any form of intractable epilepsy with seizures of various types, movement disorders and paroxysmal events, especially triggered by exercise, exertion, or fasting, and any unexplainable neurological deterioration. The basic diagnostic hallmarks of GLUT1-DS are CSF hypoglycorrhachia and lowered CSF/Blood serum glucose ratio. This is why lumbar punction should be considered more frequently than it is in practice being performed nowadays. Antiepileptic drug treatment may be ineffective or even potentially detrimental. Early identification and molecular confirmation of GLUT1-DS is important, because this is a metabolic disorder and patients should as soon as possible primarily be treated with a ketogenic diet.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Child
  • DNA Mutational Analysis
  • Epilepsy / genetics*
  • Female
  • Glucose Transporter Type 1 / deficiency*
  • Glucose Transporter Type 1 / genetics*
  • Humans
  • Male
  • Mutation
  • Neurodegenerative Diseases / genetics

Substances

  • Glucose Transporter Type 1
  • SLC2A1 protein, human