child getting eeg test for glut1 deficiency syndrome

What Is Glucose Transporter Type 1 Deficiency Syndrome (GLUT1) (SLC2A1 pathogenic variant)?

GLUT1 stands for glucose transporter protein type 1. GLUT1 deficiency is a rare genetic disorder. It is caused by variants in the SLC2A1 gene. SLC2A1 provides instructions for producing GLUT1. In the brain, the GLUT1 protein is involved in moving glucose from the bloodstream into the cerebrospinal fluid (CSF), which surrounds the brain. Glucose is the brain's main energy source. Seizures may occur when glucose is not properly transported into the brain.

Other names for GLUT1 include: glucose transporter type 1 deficiency syndrome, G1D, Glut1DS, or De Vivo Disease.

Seizures Associated with GLUT1 Deficiency

Seizures are common in GLUT1 deficiency but are not always present. Multiple seizure types may occur with both focal and generalized onset. Early onset absence seizures before the age of 3 may be a sign of GLUT1 deficiency. Seizures may begin in infancy or early childhood. Seizures tend to stabilize, decline, and sometimes eventually resolve. Standard anti-seizure medications are usually ineffective for most seizures in GLUT1 deficiency.

Non-seizure Symptoms of GLUT1 Deficiency

People with GLUT1 deficiency may have some form of complex movement disorder. This tends to be predominant in adolescence and adulthood when new types of movement episodes may appear. Most patients experience some degree of cognitive impairment. These range from subtle learning difficulties to severe intellectual disabilities. But some family members with variants in the SLC2A1 gene may be unaffected. Global developmental delay and speech/language disorders are also common. Some patients are also diagnosed with autism spectrum disorders, ADHD, and anxiety. Others report migraines, episodic confusion, memory problems, and sleep disturbances.

In many children with GLUT1 deficiency, head growth is slower than normal. This results in small head circumference for their age and can be a strong clue for this diagnosis.

All symptoms may be triggered or worsened by excessive exercise, hunger, illness, and temperature changes. Other triggers include:

  • Hormones
  • Fatigue
  • Anxiety
  • Excitement
  • Strong emotional reactions

How Is a GLUT1 Deficiency Diagnosed?

Early diagnosis is critical to initiate treatment with a ketogenic diet. The goal of early treatment is to optimize brain growth and development. This is especially important during early growth stages of life. Proper diagnosis and treatment may lead to major improvements in symptoms and quality of life at any age.

When GLUT1 deficiency is suspected, glucose is measured in the spinal fluid and in the blood. The first step is blood samples, followed by a spinal tap. Even if a spinal tap is the first test, genetic testing will help confirm the diagnosis.

The genetic test usually detects a pathogenic variant in the SLC2A1 gene. But current testing does not identify a variant in up to 5% of cases. However, the combination of symptoms and CSF findings indicate a GLUT1 deficiency diagnosis, even if there is no SLC2A1 variant. Genetic testing may be the first step if a patient has early onset absence epilepsy or early onset epilepsy with a family history of paroxysmal exercise-induced dyskinesia or other GLUT1 features. If a variant in SLC2A1 is identified, then a spinal tap may not be needed.

There are other tests that may be useful when a clear diagnosis cannot be made. These tests include PET scans and a specialized red blood cell test. These tests are only available in specialized centers.

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How Is GLUT1 Deficiency Treated?

The recommended treatment is the use of high fat, low carbohydrates diets such as the ketogenic diet. The "classic" ketogenic diet is a medical diet that helps to control seizures in some people with epilepsy. The diet can improve symptoms for many patients, even in adults. The name ketogenic means that it produces ketones in the body. Ketones are formed when the body uses fat for its source of energy. Usually the body uses carbohydrates (such as sugar, bread, pasta) for its fuel. Because the ketogenic diet is very low in carbohydrates, fats become the primary fuel instead. The body can work very well on ketones (and fats). Outcomes are better for patients when the diet is implemented early. This helps improve seizure control, movement disorders, and cognitive abilities.

All patients on a ketogenic diet should be under the care of an experienced dietitian and neurologist. They should also have regular lab tests to help monitor for potential side effects. Blood ketone levels, in addition to urine ketones, are often monitored and may be correlated to optimal brain energy supply and symptom control.

For some patients, a ketogenic diet may not work despite adequate levels of ketosis. Medications to address the symptoms of seizures or movement disorders may provide some benefit.

Occupational therapy, physical therapy, and speech and language therapies are often recommended to support optimal development in children. These therapies remain beneficial into adulthood. Many adult patients have reported that regular physical exercise can help reduce movement disorder symptoms.

How Common Is GLUT1 Deficiency?

Currently, there are hundreds of people diagnosed with GLUT1 deficiency. Recent studies have estimated true prevalence to be at least 1:24,000, so the vast majority remain undiagnosed. Gender or race don’t seem to be a factor in prevalence.

What Is the Outlook for GLUT1 Deficiency?

Disclaimer: This field is rapidly evolving, and everyone has their own course. We are constantly learning, and published data may be slow to come.

Seizures tend to stabilize in adulthood, but movement disorders may become more pronounced. There is no evidence of loss of skills over time for individuals on a ketogenic diet.

Symptoms and severity may vary greatly from one individual to another. The extent of cognitive and medical challenges may impact nearly all aspects of life. These include the level of independence individuals may attain, the types of opportunities available to them, and the services and supports they may be eligible to receive.

For More Information

Authored By: 
Glenna Steele
Professor Jörg Klepper, MD
Authored Date: 
02/2021
Reviewed By: 
Beth Rosen Sheidley MS, CGC
Annapurna Poduri MD, MPH
on: 
Thursday, September 30, 2021