motivates us all to help raise awareness
of Glut1 Deficiency Syndrome
Glut1 Deficiency is a rare genetic condition that affects brain metabolism. It is caused by a mutation in the SLC2A1 gene, which regulates the glucose transporter protein type 1 (Glut1). Glut1 is the principal transporter of glucose, the primary source of energy, across the blood-brain barrier. More than 100 different types of mutations and deletions of this gene have been found to date in Glut1 Deficiency patients.
Impaired glucose transport associated with Glut1 Deficiency creates an energy crisis in the brain and often results in seizures, speech and movement disorders, and developmental delays. Not all patients experience all symptoms, especially with the milder phenotypes. Symptoms vary and may change and evolve over time.
The standard of care treatment is a ketogenic diet. This low carbohydrate, moderate protein, high fat diet causes the body to produce ketones, which are used as an energy source by the brain and other tissues when glucose is limited. The diet helps most patients with most symptoms, even in adulthood. A ketogenic diet also helps preserve brain growth and development, so early diagnosis and treatment is critical.
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:
Natural history studies have shown that, in general, seizures improve in adulthood and movement disorders become more pronounced. Puberty often brings changes in symptoms and treatment response.
Other conditions sometimes diagnosed in patients with Glut1 Deficiency:
There is currently no cure for Glut1 Deficiency, but the recommended standard of care treatment is a medically supervised ketogenic diet, which can improve most symptoms for most patients, even in adulthood. A ketogenic diet is a high fat, moderate protein,
low carbohydrate diet that provides alternative fuel to the brain with ketones instead
of glucose. The earlier the diet is implemented, the better the outcomes for patients in improving seizure control, movement disorders, and cognitive abilities. Studies show that 4 out of 5 children who have epilepsy caused by Glut1 Deficiency will become seizure- free on dietary therapy.
In infancy and childhood, a classical 3:1 or 4:1 ketogenic is recommended to ensure the highest level of ketone energy to the meet the metabolic fuel demands of the developing brain. Although it is recommended to continue the classical ketogenic diet for as long as is tolerated by the patient, alternative ketogenic diet versions such as the Modified Ketogenic (2:1 and 1:1 ratios) or the Modified Atkins Diet may be more feasible for quality of life and compliance considerations and are often used by teenagers and adults.
All patients on a ketogenic diet should be under the care of an experienced dietitian and neurologist and have regular laboratory screenings to help monitor for potential side effects. Blood ketone levels, as opposed to urine, should also be monitored and can be correlated to optimal brain energy supply and symptom control.
For a small subset of patients, a ketogenic diet proves ineffective despite adequate levels of ketosis. Medications to address the symptoms of seizures or movement disorders may provide benefit, although there is currently no clear basis for specific recommendations and there are concerns to consider regarding potential harmful interactions with ketogenic diets.
The number of patients diagnosed is currently thought to number in the hundreds. Recent studies have estimated true prevalence to be at least 1:24,000, so the vast majority of patients remain undiagnosed. There’s no known susceptibility related to gender or race.