Glucose transporter type 1 deficiency syndrome, or Glut1 Deficiency, is a rare genetic disorder that impairs brain metabolism.
Glucose is not transported properly into the brain, which leaves it starving for the metabolic fuel it needs to grow, develop and function normally.
The condition is caused by over a hundred different mutations in the SLC2A1 gene, which regulates GLUT1 protein production.
And because it’s an autosomal dominant disorder, just one mutation in one of the two copies of the gene is enough to cause the disease.
Mutations mostly occur spontaneously, but affected patients do have a 50% chance of passing the altered gene to an offspring.
Now, normally GLUT1 is the primary transport protein that lets glucose cross the blood brain barrier, where the brain uses it as its main source of energy.
Without enough glucose, the brain will have impaired growth and function.
This leads to symptoms that vary widely between individuals, and can even evolve over time as patients age.
Typically, newborns are asymptomatic, but within a few months they sometimes develop irregular involuntary eye-head movements called aberrant gaze saccades or intermittent involuntary gaze, which is often a first sign of Glut1 Deficiency.
Various types of seizures are common in many patients but not always present. These seizures are usually resistant to medication treatments.
Most Glut1 Deficiency patients also have some form of movement disorder: spasticity where muscles are stiff and tense; ataxia, where balance and movement control is poor; and dystonia where muscles are contracted and twisted.
Episodes of temporary paralysis on one or both sides of the body, can also occur.
Puberty often brings positive or negative changes in symptoms as well as changes in the response to typical treatments.
In adulthood seizures tend to decrease for most patients, but movement symptoms can worsen.
However, not all patients experience all the symptoms, especially in milder cases.
The range and combination of symptoms can vary from mild to severe, sometimes making Glut1 deficiency difficult to diagnose.
Global developmental delays are typical for Glut1 Deficiency patients.