What is Glut1 Deficiency?
Glucose Transporter Type 1 Deficiency Syndrome
Glut1 Deficiency, G1D, Glut1 DS, or De Vivo Disease
Glucose Transporter Type 1 Deficiency Syndrome is a genetic disorder that impairs brain metabolism. Glucose isn’t transported properly into the brain, which leaves it starving for the metabolic fuel it needs to grow, develop, and function the way it should.
Glut1 Deficiency is caused by mutations in the SLC2A1 gene, which is responsible for regulating production of the glucose transporter protein type 1 (Glut1). The Glut1 protein transports glucose into cells, between cells, and across the blood-brain barrier. Glut1 is the principal transporter of glucose, the primary source of energy, across the blood-brain barrier and is key in supplying glucose to the cells of the central nervous system. More than 100 different types of mutations and deletions of this gene have been found to date in Glut1 Deficiency patients, and approximately 10-15% of patients do not show a genetic mutation.
The impaired glucose transport associated with Glut1 Deficiency causes an array of symptoms which may vary considerably from one patient to another and can change and evolve over time. Some of the most common signs and symptoms may include seizures, unusual eye-head movements in infancy, movement disorders, speech and language disorders, and developmental delays. Not all patients experience all symptoms, especially in the milder cases. There are currently a few hundred patients diagnosed worldwide, but experts believe there are thousands more yet to be discovered.
There is currently no cure for Glut1 Deficiency. Treatment is aimed at controlling symptoms by addressing what is thought to be the fundamental issue of Glut1 Deficiency – energy failure in the brain. The current standard of care treatment is a ketogenic diet, which helps improve most symptoms for most patients, even in adulthood. A ketogenic diet gives the brain an alternate source of energy and helps optimize brain growth and development.
Glut1 Deficiency Syndrome (Glut1DS): State of the Art in 2020 and Recommendations from an International Glut1DS Study Group
Could it be Glut1 Deficiency?
The hallmark symptoms of classical Glut1 Deficiency are seizures (approximately 90% of patients), a complex movement disorder, developmental delay and intellectual disability, and speech/language impairments. Not all patients experience all symptoms, and there is a great deal of variance across a wide spectrum in both the combination and severity of symptoms from one patient to another. Symptoms may also change and evolve over time as patients age.
Suggestive symptoms seen in many Glut1 Deficiency patients:
(please see our Key Terms resource for a more complete list with definitions)
Other conditions sometimes diagnosed in patients with Glut1 Deficiency:
Diagnosing Glut1 Deficiency
Lumbar Puncture:
When Glut1 Deficiency is suspected, glucose should be measured in the spinal fluid and in the blood simultaneously after a 4-6 hour fast. Blood samples should be drawn first to avoid stress-related hyperglycemia, and a lumbar puncture (spinal tap) should quickly follow.
Metabolic Hallmarks of Glut1 Deficiency:
Glucose Reference Ranges in Glut1 Deficiency:
Genetic Analysis:
Genetic testing can also help confirm the diagnosis by detecting a mutated SLC2A1 gene, although current testing doesn’t identify a mutation in 10-15% of patients. The combination of suggestive clinical symptoms and the characteristic CSF findings indicate a Glut1 Deficiency diagnosis, even in the absence of an identified SLC2A1 mutation.
Distinct patterns of brain glucose uptake on PET scans and specialized red blood cell uptake assays are also useful in the absence of an otherwise clear diagnosis but might be available in specialized centers only.
Dystonia 9 and 18 are associated with mutations in the SLC2A1 gene.
Key Terms in Glut1 Deficiency
Brochures
Professional Guide
Consensus Guidelines
Diagnostic Protocol
Additional Resources
Research Updates
Glut1 Deficiency is caused by mutations in the SLC2A1 gene, which is responsible for regulating production of the glucose transporter protein type 1 (Glut1). The Glut1 protein transports glucose into cells, between cells, and across the blood-brain barrier. Glut1 is the principal transporter of glucose, the primary source of energy, across the blood-brain barrier and is key in supplying glucose to the cells of the central nervous system. More than 100 different types of mutations and deletions of this gene have been found to date in Glut1 Deficiency patients, and approximately 10-15% of patients do not show a genetic mutation.
The impaired glucose transport associated with Glut1 Deficiency causes an array of symptoms which may vary considerably from one patient to another and can change and evolve over time. Some of the most common signs and symptoms may include seizures, unusual eye-head movements in infancy, movement disorders, speech and language disorders, and developmental delays. Not all patients experience all symptoms, especially in the milder cases. There are currently a few hundred patients diagnosed worldwide, but experts believe there are thousands more yet to be discovered.
There is currently no cure for Glut1 Deficiency. Treatment is aimed at controlling symptoms by addressing what is thought to be the fundamental issue of Glut1 Deficiency – energy failure in the brain. The current standard of care treatment is a ketogenic diet, which helps improve most symptoms for most patients, even in adulthood. A ketogenic diet gives the brain an alternate source of energy and helps optimize brain growth and development.
Glut1 Deficiency Syndrome (Glut1DS): State of the Art in 2020 and Recommendations from an International Glut1DS Study Group
Could it be Glut1 Deficiency?
The hallmark symptoms of classical Glut1 Deficiency are seizures (approximately 90% of patients), a complex movement disorder, developmental delay and intellectual disability, and speech/language impairments. Not all patients experience all symptoms, and there is a great deal of variance across a wide spectrum in both the combination and severity of symptoms from one patient to another. Symptoms may also change and evolve over time as patients age.
Suggestive symptoms seen in many Glut1 Deficiency patients:
(please see our Key Terms resource for a more complete list with definitions)
- paroxysmal exercise-induced dystonia/dyskinesia (PED) (movement episodes triggered by exercise)
- early onset absence seizures before the age of 3
- treatment resistant seizures/epilepsy at any age
- movement and balance issues (ataxia, dystonia, chorea, tremor, gait abnormalities, and others)
- fluctuation of symptoms with hunger, fatigue, heat, illness, anxiety, stress, excitement
- symptoms worse just after waking in the morning
- symptom improvement after eating
- opsoclonus-like darting and dancing eye/head movements in first two years of life (aberrant gaze saccades or intermittent involuntary gaze)
- paroxysmal neurological symptoms (transient or episodic - not there all the time)
(seizures, movement disturbances, hemiplegia episodes, headaches, energy levels, confusion, mood) - speech difficulties
- Dystonia 9 and Dystonia 18 are associated with the SLC2A1 gene and are considered part of the phenotypic spectrum
- developmental delays
- intellectual disabilities
Other conditions sometimes diagnosed in patients with Glut1 Deficiency:
- epilepsy
- cerebral palsy
- ataxia
- dystonia
- autism
- hemolytic anemia
- ADHD
- alternating hemiplegia of childhood
Diagnosing Glut1 Deficiency
Lumbar Puncture:
When Glut1 Deficiency is suspected, glucose should be measured in the spinal fluid and in the blood simultaneously after a 4-6 hour fast. Blood samples should be drawn first to avoid stress-related hyperglycemia, and a lumbar puncture (spinal tap) should quickly follow.
Metabolic Hallmarks of Glut1 Deficiency:
- low cerebrospinal fluid (CSF) glucose
- normal blood glucose
- normal cell counts
- normal CSF protein
- low to low-normal CSF lactate
Glucose Reference Ranges in Glut1 Deficiency:
- gender independent but age specific, falling at or below the 5th percentile
- fasting CSF glucose below 3.0 mmol/L or 53 mg/dl
- fasting CSF to blood glucose ratio below 60%
Genetic Analysis:
Genetic testing can also help confirm the diagnosis by detecting a mutated SLC2A1 gene, although current testing doesn’t identify a mutation in 10-15% of patients. The combination of suggestive clinical symptoms and the characteristic CSF findings indicate a Glut1 Deficiency diagnosis, even in the absence of an identified SLC2A1 mutation.
Distinct patterns of brain glucose uptake on PET scans and specialized red blood cell uptake assays are also useful in the absence of an otherwise clear diagnosis but might be available in specialized centers only.
Dystonia 9 and 18 are associated with mutations in the SLC2A1 gene.
Key Terms in Glut1 Deficiency
Brochures
Professional Guide
Consensus Guidelines
Diagnostic Protocol
Additional Resources
Research Updates
