Glut1 Deficiency Syndrome

A hereditary, usually autosomal dominant, neurologic disorder showing wide phenotypic variability and characterized by low CSF GLUCOSE (<40mg/dL) and low CSF LACTATE. The most severe cases present with infantile-onset epileptic encephalopathy, DEVELOPMENTAL DELAY, acquired MICROCEPHALY, motor incoordination, and MUSCLE SPASTICITY. Seizures typically appear during the first 4 months of life. Sudden onset of Intermittent ATAXIA; CONFUSION; LETHARGY; sleep disturbances, and HEADACHE may also occur. Cognitive impairment may range from LEARNING DISABILITIES to severe INTELLECTUAL DISABILITY. Mutations in the GLUT1 gene have been identified. OMIM: 606777

Also Known As:

Networked: 159 relevant articles (7 outcomes, 2 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Nervous System Diseases (Neurological Disorders)
2.	Metabolic Brain Diseases (Encephalopathy, Metabolic)
3.	Epilepsy (Aura)
4.	Seizures (Absence Seizure)
5.	Microcephaly

Experts

1.	De Vivo, Darryl C: 16 articles (11/2021 - 08/2002)
2.	Veggiotti, Pierangelo: 12 articles (04/2021 - 12/2013)
3.	Klepper, Joerg: 12 articles (09/2020 - 09/2007)
4.	De Giorgis, Valentina: 10 articles (09/2020 - 12/2013)
5.	Wang, Dong: 9 articles (12/2011 - 08/2002)
6.	Pascual, Juan M: 8 articles (09/2020 - 10/2002)
7.	Yang, Hong: 8 articles (01/2017 - 05/2004)
8.	Klepper, Jörg: 8 articles (11/2008 - 06/2002)
9.	Engelstad, Kristin: 7 articles (09/2020 - 10/2002)
10.	Tagliabue, Anna: 6 articles (04/2021 - 06/2014)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Glut1 Deficiency Syndrome:

1.	Glucose (Dextrose)FDA LinkGeneric 11/01/2023 - "Since genetic GLUT-1 deficiency syndrome shows a symptom spectrum similar to HE-PHD, we investigated the potential role of the two main glucose transporters, GLUT-1 and GLUT-3, in HE-PHD. " 05/26/2022 - "Glut1 deficiency syndrome is caused mainly by mutations of the SLC2A1 gene, impairing passive glucose transport across the blood-brain barrier. " 11/01/2021 - "Glut1 deficiency syndrome is caused by SLC2A1 mutations on chromosome 1p34.2 that impairs glucose transport across the blood-brain barrier resulting in hypoglycorrhachia and decreased fuel for brain metabolism. " 11/01/2021 - "Glucose Transporter-1 (GLUT1) Deficiency Syndrome (GLUT1DS) is caused by defective transport of glucose across the blood-brain barrier into brain cells resulting in hypoglycorrhachia due to the heterozygous pathogenic variants in SLC2A1. " 11/01/2020 - "We detected that HFD predisposes towards seizure development in the PTZ-kindling model and this was linked to a reduction in glucose transporter-1 (GLUT-1) expression as observed in GLUT-1 deficiency syndrome in humans but accompanied by a compensatory increase in expression of GLUT-3. "
2.	Glucose Transporter Type 1IBA 01/01/2023 - "Ketogenic Dietary Treatments (KDTs) are to date the gold-standard treatment for glucose transporter type 1 (GLUT1) deficiency syndrome. " 01/01/2021 - "Glucose transporter type 1 (GLUT1) is the most important energy carrier of the brain across the blood-brain barrier, and a genetic defect of GLUT1 is known as GLUT1 deficiency syndrome (GLUT1DS). " 07/01/2017 - "Glucose transporter type 1 (GLUT1) deficiency syndrome (GLUT1-DS) leads to a wide range of neurological symptoms. " 01/01/2016 - "Glucose transporter type 1 deficiency syndrome is due to de novo mutations in the SLC2A1 gene encoding the glucose transporter type 1. Paroxysmal motor manifestations induced by exercise or fasting may be the main manifestations of glucose transporter type 1 deficiency syndrome. " 06/01/2005 - "We report the first two Japanese children diagnosed with glucose transporter type 1 (GLUT1) deficiency syndrome. "
3.	Biomarkers (Surrogate Marker)IBA 01/01/2023 - "We used next-generation metabolic screening to identify new biomarkers for improved diagnosis and pathophysiological understanding of glucose transporter type 1 deficiency syndrome (GLUT1DS), comparing metabolic cerebrospinal fluid (CSF) profiles from 12 patients to those of 116 controls. " 01/01/2023 - "Novel cerebrospinal fluid biomarkers of glucose transporter type 1 deficiency syndrome: Implications beyond the brain's energy deficit." 01/01/2017 - "Glucose transporter type 1 deficiency syndrome (GLUT1DS) is a neurometabolic disorder with a complex phenotypic spectrum but simple biomarkers in cerebrospinal fluid. " 01/01/2017 - "To provide imaging biomarkers of generalized spike-and-wave discharges (GSWD) in patients with GLUT1 deficiency syndrome (GLUT1DS). " 11/01/2013 - "Future availability of whole-exome sequencing in clinical practice will make the existence of a reliable biomarker for GLUT1 deficiency syndrome even more important, in order to interpret genetic results and, even more importantly, not to miss SLC2A1-negative patients with GLUT1 deficiency syndrome."
4.	triheptanoinIBA 11/01/2019 - "Long-term follow-up in an open-label trial of triheptanoin in GLUT1 deficiency syndrome: a sustained dramatic effect." 01/01/2020 - "Transition from ketogenic diet to triheptanoin in patients with GLUT1 deficiency syndrome." 05/01/2016 - "On the basis of our previous work with triheptanoin, which provides key substrates to the Krebs cycle in the brain, we wished to assess its therapeutic effect in patients with glucose transporter type 1 deficiency syndrome (GLUT1-DS) who objected to or did not tolerate ketogenic diets. " 12/01/2022 - "Triheptanoin for epilepsy secondary to glucose transporter 1 ( GLUT1 ) deficiency syndrome is not clearly effective but further studies will be needed."
5.	Facilitative Glucose Transport Proteins (Glucose Transporter)IBA 02/01/2014 - "Glucose transporter type 1 deficiency syndrome is caused by heterozygous, mostly de novo, mutations in the SLC2A1 gene encoding the glucose transporter GLUT1. " 08/01/2002 - "Glut-1 deficiency syndrome (Glut-1 DS) is caused by the deficiency of the major glucose transporter in cerebral microvessels. " 11/01/2016 - "Glucose transporter 1 (GLUT1) deficiency syndrome (GLUT1DS) was initially described in the early 90s as a sporadic clinical condition, characterized by seizures, motor and intellectual impairment with variable clinical presentation, and without a known genetic cause. " 03/01/2014 - "GLUT-1 deficiency syndrome is a rare genetic disease where the specific glucose transporter through the brain barrier is deficient. " 05/12/2006 - "GLUT1 is essential for human brain development and function, as evidenced by the severe epileptic encephalopathy observed in children with GLUT1 deficiency syndrome resulting from inherited loss-of-function mutations in the gene encoding this facilitative glucose transporter. "
6.	Proteins (Proteins, Gene)FDA Link 01/01/2018 - "Follow-up experiments on GLUT1 (SLC2A1), the glucose transporter causative of GLUT1 deficiency syndrome, revealed that the mutated protein mislocalizes to intracellular compartments. " 01/01/2017 - "Brain microvasculature defects and Glut1 deficiency syndrome averted by early repletion of the glucose transporter-1 protein." 12/01/2019 - "Dysfunction of glucose transporter 1 (GLUT1) proteins causes infantile epilepsy, which is designated as a GLUT1 deficiency syndrome (GLUT1DS; OMIM #606777). " 01/01/2019 - "Paucity of the protein stemming from mutations in the associated SLC2A1 gene deprives the brain of glucose and triggers the infantile-onset neurodevelopmental disorder, Glut1 deficiency syndrome (Glut1 DS). " 04/01/2020 - "Glucose Transporter Type 1 Deficiency Syndrome (GLUT1-DS) is caused by the SLC2A1 gene muta tion, which encodes the glucose transporter proteins to the brain Neurological manifestations occur in three main domains: seizures, abnormal movements, and cognitive disorders. "
7.	KetonesIBA 08/01/2013 - "As high ketones appear essential to meet the brain energy deficit caused by Glut1 deficiency syndrome, the use of novel ketogenic diets in this entity may be limited. " 05/01/2019 - "Epilepsy in GLUT1 deficiency syndrome is generally drug-resistant; ketogenic diet (KD) therapy is the mainstay of therapy, as production of ketones provides the brain with an alternative energy source, bypassing the defect in GLUT1. " 11/01/2021 - "Standard treatment for Glut1 deficiency syndrome is the ketogenic diet that decreases the demand for brain glucose by supplying ketones as alternative fuel. " 08/15/2020 - "The effect of KD, butanediol (BD), ketone-ester (KE), ketone-salt (KS), and their combination (KE + KS: KEKS) or mixtures with medium chain triglyceride (MCT) (KE + MCT: KEMCT; KS + MCT: KSMCT) was tested in Sprague-Dawley (SPD) and WAG/Rij (WR) rats and in GLUT-1 Deficiency Syndrome (G1D) mice. "
8.	CarbohydratesIBA 01/01/2011 - "We report a 3-year-old girl affected by glucose transporter type 1 deficiency syndrome with carbohydrate responsiveness. " 01/01/2011 - "Pre- and postprandial electroencephalography in glucose transporter type 1 deficiency syndrome: an illustrative case to discuss the concept of carbohydrate responsiveness." 12/01/2011 - "Glucose transporter type 1 deficiency syndrome with carbohydrate-responsive symptoms but without epilepsy." 01/01/2013 - "Treatment of these disorders involves the avoidance of fasting, dietary treatment eliminating specific carbohydrates, and enzyme replacement therapy in individual glycogen storage diseases.GLUT1 deficiency syndrome, a specific disorder of glucose transport into brain, results in global developmental delay, early-onset epilepsy, and a complex movement disorder. "
9.	Lactic Acid (Lactate)FDA LinkGeneric 01/01/2016 - "Lactate is thought to be an alternative fuel in the brain of patients with glucose transporter type 1 deficiency syndrome and glycogen storage disease, and it has been demonstrated that lactate might have a protective role in ischemic and traumatic brain injury. " 11/01/2013 - "We conclude that if age-specific reference values are applied, CSF glucose and lactate levels are adequate biomarkers in the diagnostic workup of GLUT1 deficiency syndrome. " 11/01/2013 - "A typical CSF profile for GLUT1 deficiency syndrome, which is defined as a CSF glucose level at or below the 10th percentile, a CSF to blood glucose ratio at or below the 25th percentile, and a CSF lactate level at or below the 10th percentile, was found in only 35 of 4099 CSF samples (0.9%) present in our CSF database of patients who received a diagnosis other than GLUT1 deficiency syndrome. "
10.	LipidsIBA 03/01/2004 - "The effects of the KD in GLUT1 deficiency syndrome, particularly the course of blood lipids, are discussed in an illustrative case. " 11/01/2008 - "Our results indicate a characteristic effect of a long-term ketogenic diet on glucose and lipid homeostasis in Glut1 deficiency syndrome. "

Therapies and Procedures

1.	Ketogenic Diet 07/01/2023 - "The ketogenic diet is the treatment of GLUT1 deficiency syndrome that provides an alternative energy source for the brain. " 07/01/2023 - "Nutritional Intervention Through Ketogenic Diet in GLUT1 Deficiency Syndrome." 01/01/2023 - "Long-term follow-up of nutritional status in children with GLUT1 Deficiency Syndrome treated with classic ketogenic diet: a 5-year prospective study." 10/27/2022 - "Therefore, patients with glucose transporter type 1 deficiency syndrome caused by SLC2A1 mutations should begin ketogenic diet treatment as soon as possible." 03/01/2022 - "Further investigation of the cerebrospinal fluid revealed hypoglycorrhachia that was the clue to the diagnosis of Glut1 deficiency syndrome and the initiation of treatment with ketogenic diet. "
2.	High-Protein Low-Carbohydrate Diet (Atkins Diet) 04/01/2014 - "Glucose transporter type 1 deficiency syndrome effectively treated with modified Atkins diet." 11/01/2016 - "Use of modified Atkins diet in glucose transporter type 1 deficiency syndrome." 04/01/2014 - "This is a report on the successful treatment of a 6-year-old girl with genetically proven glucose transporter type 1 deficiency syndrome (GLUT1-DS) with modified Atkins diet (MAD). " 07/01/2011 - "A modified Atkins diet is promising as a treatment for glucose transporter type 1 deficiency syndrome." 03/04/2021 - "Classic Ketogenic Diet and Modified Atkins Diet in SLC2A1 Positive and Negative Patients with Suspected GLUT1 Deficiency Syndrome: A Single Center Analysis of 18 Cases."
3.	Therapeutics 02/01/2016 - "Use of dietary therapies amongst patients with GLUT1 deficiency syndrome." 10/01/2015 - "We aimed to determine whether response to ketogenic dietary therapies (KDT) was due to undiagnosed glucose transporter type 1 deficiency syndrome (GLUT1-DS). " 01/01/2021 - "A 19-year-old woman with glucose transporter type 1 deficiency syndrome (Glut1DS) treated with ketogenic diet therapy (KDT) became pregnant. " 11/02/2020 - "Objective: To explore the clinical characteristics of pediatric glucose transporter type 1 deficiency syndrome (GLUT1 DS), evaluate the efficacy and safety of ketogenic diet therapy (KDT). " 11/02/2020 - "[Clinical characteristics and ketogenic diet therapy of glucose transporter type 1 deficiency syndrome in children: a multicenter clinical study]."
4.	Enzyme Replacement Therapy 01/01/2013 - "Treatment of these disorders involves the avoidance of fasting, dietary treatment eliminating specific carbohydrates, and enzyme replacement therapy in individual glycogen storage diseases.GLUT1 deficiency syndrome, a specific disorder of glucose transport into brain, results in global developmental delay, early-onset epilepsy, and a complex movement disorder. "
5.	Intravenous Anesthesia 05/05/2019 - "Total Intravenous Anesthesia in GLUT1 Deficiency Syndrome Patient: A Case Report."