What is Glut1 DS?

INTRODUCTION
INHERITANCE
SIGNS AND SYMPTOMS
GETTING DIAGNOSED

Introduction

Glut1 DS stands for glucose transporter type-1 deficiency syndrome. (It is also known as Glut1 deficiency, Glut1D, and De Vivo Disease.) It is a rare disease affecting between 3000 and 7000 people in the United States and is caused by a mutation of the SLC2A1 gene.1

Glut1 DS interferes with the ability of glucose—the body’s primary energy source—to cross the blood-brain barrier. Glucose normally gets into the brain through a ‘vehicle’ called a Glut1 transporter. In people with a mutation in the SLC2A1 gene, the Glut1 transporter does not work properly and not enough glucose can get to the brain. This leaves the brain starving for fuel and can lead to symptoms, such as2:

  • Seizures or epilepsy
  • Movement disorders
  • Developmental delays or learning difficulties

Life With Glut1 DS: Oliver’s Story

Inheritance

About 90% of people with Glut1 DS are the first person in their families to have the disease. In this case, the disease typically arises from a new mutation in the gene associated with
Glut1 DS.2

People with Glut1 DS have a 50% chance of passing the disease on to each child3

Glut1 DS is usually inherited in an autosomal dominant pattern, which means that a child with one copy of the SLC2A1 gene mutation from either their mother or father will have the disease.3

Autosomal Dominant

Signs and symptoms

When the brain doesn’t get enough energy, it can result in a range of symptoms, including2,4:

Seizures

Seizures may appear differently in each person, and not all people affected by Glut1 DS have seizures. Absence seizures, in which a person appears to lose awareness or stares into space for a short time, are common in Glut1 DS.

Movement disorders

People with Glut1 DS may experience abnormal limb movements such as twitching, flailing, writhing and poor balance. These can be ongoing or occasional. Problems walking or running may be a sign of a movement disorder. Additionally, abnormal, involuntary eye movements that cannot be controlled have been found in people with Glut1 DS.

Developmental delay

Children affected by Glut1 DS may experience motor (movement) and developmental delay including learning disabilities and language difficulties.

Classic Glut1 DS2,3

Most people with Glut1 DS have seizures or a combination of seizures, movement disorders, and learning difficulties. Seizures may be the first symptom noticed because the onset usually occurs before 2 years of age. Movement disorders and developmental delays can start in infancy, but they usually become more apparent during childhood.

When an infant with seizures doesn’t respond as expected to antiepileptic drugs (AEDs), that may be the first sign that the underlying cause could be Glut1 DS. Signs of movement disorders and developmental delays provide a further indication that the underlying cause could be Glut1 DS.

However, we now know that not all people with Glut1 DS have seizures or all three categories of symptoms.

Nonclassic Glut1 DS2

People with nonclassic Glut1 DS may not have seizures. They may develop movement disorders and/or learning disabilities. When the underlying cause is Glut1 DS, getting a diagnosis of the underlying cause is the first step in getting appropriate treatment.

Common seizure types5

Generalized tonic-clonic (grand mal): Alternating convulsions and muscle rigidity

Absence: Brief loss of consciousness (moments of blank staring)

Myoclonic: Sporadic (isolated) jerking movements

Clonic: Repetitive jerking movements

Tonic: Muscle stiffness, rigidity

Atonic (drop): Loss of muscle tone

Classic Glut1 DS2

Only:

  • Seizures

Or a combination of:

  • Seizures or epilepsy
  • Movement disorders
  • Developmental delays

Nonclassic Glut1 DS2

One or both:

  • Movement disorders
  • Developmental delays

Getting diagnosed with Glut1 DS

Importance of an accurate diagnosis2,3

Because Glut1 DS is rare, many health care providers don’t test for it right away. Infants with seizures are often started on antiepileptic drugs (AEDs) to reduce the frequency and severity of the seizures. However, when the underlying cause is Glut1 DS, these medicines don’t always work as expected. Furthermore, AEDs have no benefit for treating movement disorders or cognitive impairment, which may not be apparent in infancy. Getting an accurate diagnosis is the first step toward helping to manage Glut1 DS.

Challenges in diagnosing Glut1 DS3,6

If the doctor suspects Glut1 DS, a common method of diagnosis involves a procedure called a lumbar puncture, also known as a spinal tap. The levels of glucose in the spinal fluid can be compared to the levels of glucose in the blood to determine how much glucose is getting across the blood-brain barrier.

Modern genetic testing has now made another method of diagnosis possible. Mutations of the SLC2A1 gene (a cause of Glut1 DS) occur in 80%-90% of people with Glut1 DS. Genetic testing, using a blood test, can help confirm a Glut1 DS diagnosis. The test may not identify a mutation in all people who have Glut1 DS. A negative test result does not necessarily mean you do not have Glut1 DS.

Genetic testing for Glut1 DS is available at no cost to you or your insurance company, whether the test shows mutations in the SLC2A1 gene or not. Download the genetic testing discussion guide.

Ask your doctor if genetic testing is right for you.

LEARN ABOUT GENETIC TESTING >

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References: 1. US National Library of Medicine. Glut1 deficiency syndrome. http://ghr.nlm.nih.gov/condition/glut1-deficiency-syndrome. Updated March 2014. Accessed April 27, 2016. 2. Pearson TS, Akman C, Hinton VJ, Engelstad K, De Vivo DC. Phenotypic spectrum of glucose transporter type 1 deficiency syndrome (Glut1 DS). Curr Neurol Neurosci Rep. 2013;13(4):342-350. doi:10.1007/s11910-013-0342-7. 3. Wang D, Pascual JM, De Vivo D. Glucose transporter type 1 deficiency syndrome. In: Pagon RA, Adam MP, Ardinger HH, et al, eds. GeneReviews® [Internet]. Seattle, WA: University of Washington, Seattle; 1993-2016. http://www.ncbi.nlm.nih.gov/books/NBK1430/. Published July 30, 2002. Updated January 22, 2015. 4. De Giorgis V, Veggiotti P. Glut1 deficiency syndrome 2013: current state of the art. Seizure. 2013;22(10):803-811. doi:10.1016/j.seizure.2013.07.003. 5. Pong AW, Geary BR, Engelstad KM, Natarajan A, Yang H, DeVivo DC. Glucose transporter type 1 deficiency syndrome: epilepsy phenotypes and outcomes. Epilepsia. 2012;53(9):1503-1510. doi:10.1111/j.1528-1167.2012.03592.x. 6.Verrotti A, D’Egidio C, Agostinelli S, Gobbi G. Glut1 deficiency: when to suspect and how to diagnose? Eur J Pediatr Neurology. 2012;16(1):3-9.