Glucose Transporter Type 1 Deficiency
Our primary concern as Matthew's Friends is the use of the ketogenic diet to treat childhood epilepsies. However, we feel that it is important to offer information of other areas where the diet has proved useful. The following information has been provided by Dr. Joerg Klepper, a world expert in this field:
Joerg Klepper PD Dr. med.
In certain metabolic diseases affecting brain energy metabolism the ketogenic diet is the treatment of choice.
GLUT1 deficiency syndrome is such a disorder. Glucose is the essential fuel for brain metabolism A defect in the GLUT1-transporter at the blood-brain barrier results in insufficient glucose transfer – the result is an “energy crisis” in brain. Here the ketogenic diet provides ketones as an alternative fuel to restore brain energy metabolism. Most patients become seizure-free on the diet and improve in motor and mental development. We know of 84 patients with this entity worldwide and currently follow 20 patients at our institution. Research is going on to understand this treatable disease and to provide novel therapies in the future.
In intractable childhood epilepsy unresponsive to anticonvulsant drugs the ketogenic diet is now increasingly recognized as an effective treatment alternative. Researchers worldwide have developed an increasing interest in the ketogenic diet and provided exciting novel insights into anticonvulsive and disease mechanisms. Our current efforts along with other experts in the field are are aiming to establish international treatment protocols and coordinate research efforts worldwide. This will improve our understanding of ketogenic diet mechanisms and treatment effects. Establishing standard protocols will also help to establish novel indications for the diet and coordinate research efforts worldwide.
Thanks for all your work - Matthews friends is an excellent organisation and site!
PD Dr. med.
Medical director of Childrens’ Hospital Aschaffenburg, Germany
affiliated to the University of Würzburg, Germany
A short interview with Dr. Klepper
GLUT 1 workshop
|PD Dr. Jörg Klepper
|Medical degree||Frankfurt and Würzburg University, Germany|
|Paediatric training||Würzburg und Essen University, Germany|
|Postdoc fellowship||Columbia University, New York, USA|
|Consultant for paediatric neurology||Essen University, Germany|
|Lecturer for Paediatrics||Essen University
Fields of clinical and research interest
My main field of work are disorders of brain energy metabolism such as GLUT1 deficiency syndrome or pyruvate dehydrogenase deficiency. Both disorders are associated with intractable epilepsy and respond to the ketogenic diet. Research interests are mechanisms and adverse effects of the diet, as well as establishing international protocols for the use of the diet in epilepsy and metabolic disorders.
Neuropaedric Society (German-speaking countries; board member)
European Paediatric Neurology Society (board member)
Klepper J, Leiendecker B (2007) GLUT1 deficiency syndrome – update 2007. Dev Med Child Neurol, Dev Med Child Neurol. 2007 Sep;49(9):707-16. Review
Klepper J, Scheffer H, Leiendecker B, Gertsen E, Binder S, Leferink M, Hertzberg C, Nake A, Voit T, Willemsen MA Seizure control and acceptance of the ketogenic diet in GLUT1 deficiency syndrome: a 2- to 5-year follow-up of 15 children enrolled prospectively. Neuropediatrics. 2005 Oct;36(5):302-8.
Klepper J, Salas-Burgos A, Gertsen E, Fischbarg J. Bench meets bedside: a 10-year-old girl and amino acid residue glycine 75 of the facilitative glucose transporter GLUT1. Biochemistry. 2005 Sep 27;44(38):12621-6.
Ito Y, Gertsen E, Oguni H, Nakayama T, Matsuo M, Funatsuka M, Voit T, Klepper J, Osawa M. Clinical presentation, EEG studies, and novel mutations in two cases of GLUT1 deficiency syndrome in Japan. Brain Dev. 2005 Jun;27(4):311-7.
Klepper J. Impaired glucose transport into the brain: the expanding spectrum of glucose transporter type 1 deficiency syndrome. Curr Opin Neurol 2004 Apr;17(2):193-6.
Klepper J, Leiendecker B, Riemann E, Baumeister FA. [The ketogenic diet in German-speaking countries: update 2003] Klin Padiatr. 2004 Sep-Oct;216(5):277-85. German.
Seidner G, Garcia-Alvarez M, Yeh JI, O'Driscoll K, Klepper J, R, Stump TS, Wang D, Spinner NB, Birnbaum MJ, De Vivo DC. Glut-1 deficiency syndrome caused by haploinsufficiency of the blood-brain barrier hexose carrier. Nature Gen 1998;18:1-4
The following information is provided courtesy of CLIMB - Children Living with Inherited Metabolic Diseases.
Other names for this condition are:
· De Vivo Disease
· Glucose Transporter Protein Syndrome
· Glucose Transporter Type 1 Deficiency Syndrome
· GLUT1 Deficiency
Glucose Transporter Type 1 Deficiency is a rare disorder characterized by infantile seizures, developmental delay and learning disabilities. Glucose Transporters are part of glycoproteins, which are involved in transporting glucose to most cells in the body. This disorder is caused by defects on the Glucose Transporter Type 1 Deficiency gene (SLC2A1) which encodes the Glut-1 protein. This gene is located on the short arm of chromosome 1.
This disorder is inherited by a method called autosomal dominant inheritance. One set of genes comes from the mother and one set of genes comes from the father. This method of inheritance is when a single copy of the diseased gene will dominate the other normal gene. Therefore, if a defective gene is inherited from either parent the child will be affected with the disorder. This means for each pregnancy if either of the parents has a defective gene, there is a 50% chance of a child being affected by the disease. These are general descriptions of the methods of inheritance, for further information a genetic counselling service should be consulted.
Symptoms of Glucose Transporter Type 1 Deficiency are not present at birth and do not usually show until infancy. Symptoms include low glucose levels in the fluid that surrounds the brain and spinal cord (hypoglycorrhachia), a small head (microcephaly), involuntary uncoordinated movements (ataxia), erratic eye movements such as rolling of the eyes (opsoclonus), unclear pronunciation of words (dysarthia), decreased muscle tone (hypotonia), movement and posture abnormalities and paralysis of one side (hemiparesis) or both sides of the body. Other symptoms include the child becoming inactive and unresponsive, sometimes verging on unconsciousness, a hypnotic-like trance (somnolence), confusion, epilepsy, sleep disturbances and recurrent headaches.
Diagnosis of Glucose Transporter Type 1 Deficiency is made through clinical tests, as the disorder is not apparent at birth prenatal diagnosis is not usually available. Treatment of this disorder includes a ketogenic diet in which most carbohydrates are replaced by fats and proteins. This diet has been known to help control seizures. Those affected by this disorder are recommended to avoid drugs called barbiturates and methylxanthines. Methylxanthines are found in coffee and other caffeine related products. Genetic counselling is recommended.
This information is fully sourced and referenced, for more detailed information and references please contact CLIMB by email, letter or telephone.
This information about metabolic diseases is provided by Climb and is intended for educational purposes only. It should not be used for diagnostic or treatment purposes. Should you require more detailed information please contact Climb by email (firstname.lastname@example.org) or by telephone (0800 652 3181). For specific medical information regarding a particular disease or individual please contact your GP or Paediatrician.
Climb accepts no responsibility for any errors or omissions nor does Climb assume any liability of any kind for the content of any information contained within this summary or any use that you may make of it.
Glut 1 chat site for help and support:
Following is a link that one of our parents kindly sent us to demonstrate the random episodic eye movements that can occur in Glut1:www.youtube.com/watch?v=_-M0dj_M49M