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GLUT1 deficiency syndrome

Reviewed March 2014

What is GLUT1 deficiency syndrome?

GLUT1 deficiency syndrome is a disorder affecting the nervous system that can have a variety of neurological signs and symptoms. Approximately 90 percent of affected individuals have a form of the disorder often referred to as common GLUT1 deficiency syndrome. These individuals generally have frequent seizures (epilepsy) beginning in the first months of life. In newborns, the first sign of the disorder may be involuntary eye movements that are rapid and irregular. Babies with common GLUT1 deficiency syndrome have a normal head size at birth, but growth of the brain and skull is often slow, which can result in an abnormally small head size (microcephaly). People with this form of GLUT1 deficiency syndrome may have developmental delay or intellectual disability. Most affected individuals also have other neurological problems, such as stiffness caused by abnormal tensing of the muscles (spasticity), difficulty in coordinating movements (ataxia), and speech difficulties (dysarthria). Some experience episodes of confusion, lack of energy (lethargy), headaches, or muscle twitches (myoclonus), particularly during periods without food (fasting).

About 10 percent of individuals with GLUT1 deficiency syndrome have a form of the disorder often known as non-epileptic GLUT1 deficiency syndrome, which is usually less severe than the common form. People with the non-epileptic form do not have seizures, but they may still have developmental delay and intellectual disability. Most have movement problems such as ataxia or involuntary tensing of various muscles (dystonia); the movement problems may be more pronounced than in the common form.

Several conditions that were originally given other names have since been recognized to be variants of GLUT1 deficiency syndrome. These include paroxysmal choreoathetosis with spasticity (dystonia 9); paroxysmal exercise-induced dyskinesia and epilepsy (dystonia 18); and certain types of epilepsy. In rare cases, people with variants of GLUT1 deficiency syndrome produce abnormal red blood cells and have uncommon forms of a blood condition known as anemia, which is characterized by a shortage of red blood cells.

How common is GLUT1 deficiency syndrome?

GLUT1 deficiency syndrome is a rare disorder. Approximately 500 cases have been reported worldwide since the disorder was first identified in 1991. In Australia, the prevalence of the disorder has been estimated at 1 in 90,000 people. However, researchers suggest that the disorder may be underdiagnosed, because many neurological disorders can cause similar symptoms.

What genes are related to GLUT1 deficiency syndrome?

GLUT1 deficiency syndrome is caused by mutations in the SLC2A1 gene. This gene provides instructions for producing a protein called the glucose transporter protein type 1 (GLUT1). The GLUT1 protein is embedded in the outer membrane surrounding cells, where it transports a simple sugar called glucose into cells from the blood or from other cells for use as fuel.

In the brain, the GLUT1 protein is involved in moving glucose, which is the brain's main energy source, across the blood-brain barrier. The blood-brain barrier acts as a boundary between tiny blood vessels (capillaries) and the surrounding brain tissue; it protects the brain's delicate nerve tissue by preventing many other types of molecules from entering the brain. The GLUT1 protein also moves glucose between cells in the brain called glia, which protect and maintain nerve cells (neurons).

SLC2A1 gene mutations reduce or eliminate the function of the GLUT1 protein. Having less functional GLUT1 protein reduces the amount of glucose available to brain cells, which affects brain development and function.

Related Gene(s)

Changes in this gene are associated with GLUT1 deficiency syndrome.

  • SLC2A1

How do people inherit GLUT1 deficiency syndrome?

This condition is usually inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. About 90 percent of cases of GLUT1 deficiency syndrome result from new mutations in the gene. These cases occur in people with no history of the disorder in their family. In other cases, an affected person inherits the mutation from an affected parent.

In a small number of families, GLUT1 deficiency syndrome is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of GLUT1 deficiency syndrome?

These resources address the diagnosis or management of GLUT1 deficiency syndrome and may include treatment providers.

  • G1D Registry (https://www.g1dregistry.org/)
  • Gene Review: Glucose Transporter Type 1 Deficiency Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1430)
  • Genetic Testing Registry: Glucose transporter type 1 deficiency syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1847501)
  • The Glucose Transporter Type 1 Deficiency Syndrome Research Consortium (G1DRC) (http://www.utsouthwestern.edu/education/medical-school/departments/neurology/programs/rare-brain-disorders/g1drc.html)

You might also find information on the diagnosis or management of GLUT1 deficiency syndrome in Educational resources (http://www.ghr.nlm.nih.gov/condition/glut1-deficiency-syndrome/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/glut1-deficiency-syndrome/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about GLUT1 deficiency syndrome?

You may find the following resources about GLUT1 deficiency syndrome helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for GLUT1 deficiency syndrome?

  • De Vivo disease
  • encephalopathy due to GLUT1 deficiency
  • G1D
  • glucose transport defect, blood-brain barrier
  • glucose transporter protein syndrome
  • glucose transporter type 1 deficiency syndrome
  • Glut1 deficiency
  • GLUT1 DS
  • GTPS

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about GLUT1 deficiency syndrome?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding GLUT1 deficiency syndrome?

anemia ; ataxia ; autosomal ; autosomal dominant ; autosomal recessive ; blood-brain barrier ; capillaries ; cell ; deficiency ; developmental delay ; disability ; dysarthria ; dyskinesia ; dystonia ; encephalopathy ; epilepsy ; epileptic ; fasting ; gene ; glia ; glucose ; inherited ; involuntary ; lethargy ; microcephaly ; mutation ; myoclonus ; nervous system ; neurological ; prevalence ; protein ; recessive ; sign ; simple sugar ; spasticity ; syndrome ; tissue

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Brockmann K. The expanding phenotype of GLUT1-deficiency syndrome. Brain Dev. 2009 Aug;31(7):545-52. doi: 10.1016/j.braindev.2009.02.008. Epub 2009 Mar 21. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19304421?dopt=Abstract)
  • Gene Review: Glucose Transporter Type 1 Deficiency Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1430)
  • Klepper J, Scheffer H, Elsaid MF, Kamsteeg EJ, Leferink M, Ben-Omran T. Autosomal recessive inheritance of GLUT1 deficiency syndrome. Neuropediatrics. 2009 Oct;40(5):207-10. doi: 10.1055/s-0030-1248264. Epub 2010 Mar 10. (http://www.ncbi.nlm.nih.gov/pubmed/20221955?dopt=Abstract)
  • Klepper J. GLUT1 deficiency syndrome in clinical practice. Epilepsy Res. 2012 Jul;100(3):272-7. doi: 10.1016/j.eplepsyres.2011.02.007. Epub 2011 Mar 5. Review. (http://www.ncbi.nlm.nih.gov/pubmed/21382692?dopt=Abstract)
  • Leen WG, Klepper J, Verbeek MM, Leferink M, Hofste T, van Engelen BG, Wevers RA, Arthur T, Bahi-Buisson N, Ballhausen D, Bekhof J, van Bogaert P, Carrilho I, Chabrol B, Champion MP, Coldwell J, Clayton P, Donner E, Evangeliou A, Ebinger F, Farrell K, Forsyth RJ, de Goede CG, Gross S, Grunewald S, Holthausen H, Jayawant S, Lachlan K, Laugel V, Leppig K, Lim MJ, Mancini G, Marina AD, Martorell L, McMenamin J, Meuwissen ME, Mundy H, Nilsson NO, Panzer A, Poll-The BT, Rauscher C, Rouselle CM, Sandvig I, Scheffner T, Sheridan E, Simpson N, Sykora P, Tomlinson R, Trounce J, Webb D, Weschke B, Scheffer H, Willemsen MA. Glucose transporter-1 deficiency syndrome: the expanding clinical and genetic spectrum of a treatable disorder. Brain. 2010 Mar;133(Pt 3):655-70. doi: 10.1093/brain/awp336. Epub 2010 Feb 2. (http://www.ncbi.nlm.nih.gov/pubmed/20129935?dopt=Abstract)
  • Leen WG, Wevers RA, Kamsteeg EJ, Scheffer H, Verbeek MM, Willemsen MA. Cerebrospinal fluid analysis in the workup of GLUT1 deficiency syndrome: a systematic review. JAMA Neurol. 2013 Nov;70(11):1440-4. doi: 10.1001/jamaneurol.2013.3090. Review. (http://www.ncbi.nlm.nih.gov/pubmed/23999624?dopt=Abstract)
  • Pascual JM, Wang D, Hinton V, Engelstad K, Saxena CM, Van Heertum RL, De Vivo DC. Brain glucose supply and the syndrome of infantile neuroglycopenia. Arch Neurol. 2007 Apr;64(4):507-13. Epub 2007 Feb 12. (http://www.ncbi.nlm.nih.gov/pubmed/17296829?dopt=Abstract)
  • Pascual JM, Wang D, Lecumberri B, Yang H, Mao X, Yang R, De Vivo DC. GLUT1 deficiency and other glucose transporter diseases. Eur J Endocrinol. 2004 May;150(5):627-33. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15132717?dopt=Abstract)
  • Pearson TS, Akman C, Hinton VJ, Engelstad K, De Vivo DC. Phenotypic spectrum of glucose transporter type 1 deficiency syndrome (Glut1 DS). Curr Neurol Neurosci Rep. 2013 Apr;13(4):342. doi: 10.1007/s11910-013-0342-7. Review. (http://www.ncbi.nlm.nih.gov/pubmed/23443458?dopt=Abstract)
  • Rotstein M, Engelstad K, Yang H, Wang D, Levy B, Chung WK, De Vivo DC. Glut1 deficiency: inheritance pattern determined by haploinsufficiency. Ann Neurol. 2010 Dec;68(6):955-8. doi: 10.1002/ana.22088. (http://www.ncbi.nlm.nih.gov/pubmed/20687207?dopt=Abstract)
  • Wang D, Pascual JM, Yang H, Engelstad K, Jhung S, Sun RP, De Vivo DC. Glut-1 deficiency syndrome: clinical, genetic, and therapeutic aspects. Ann Neurol. 2005 Jan;57(1):111-8. (http://www.ncbi.nlm.nih.gov/pubmed/15622525?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: March 2014
Published: October 20, 2014