Glut1 deficiency syndrome (Glut1 Deficiency Foundation)

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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.
Tremors and other involuntary movements such as chorea and dyskinesia are also common, as well as floppiness due to decreased muscle tone.
Episodes of temporary paralysis on one or both sides of the body, can also occur. These symptoms can be constant or paroxysmal, meaning intermittent, and can be triggered or worsened by excessive exercise, stress, illness, hunger, weather changes, anxiety, excitement, or fatigue.
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.
Other symptoms may include confusion, lack of physical endurance, attention deficits, anxiety, mood disturbances, frequent headaches, and sometimes characteristics along the autism spectrum.
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. Children with Glut1 Deficiency may reach developmental milestones, such as walking and speaking, at a delayed rate.
Fine motor and visual motor skills may be affected, including writing. Gross motor delays may affect core body strength, balance, and coordination.
Speech delays may affect the articulation of expressive language. Developmental delays can vary depending on the individual and the overall severity of the case.
Most patients experience some degree of intellectual disability. Additionally, because brain development is affected, patients may have microcephaly, which is when a child’s head is smaller than expected for their age or family.
Early diagnosis is crucial in order to start treatment so brain growth and development can be preserved during the important early growth stages of life.
A lumbar puncture, or spinal tap, is an important part of the diagnostic work-up, since glucose levels, and often lactate, in the spinal fluid will be low.
Genetic testing is often the first test performed today and can also help confirm the diagnosis by detecting a mutated SLC2A1 gene, although current testing doesn’t find a mutation in 10-15% of patients.
Now, there is currently no cure for Glut1 Deficiency. The recommended standard of care treatment is a medically supervised ketogenic diet, which can improve most symptoms for most patients, even in adulthood.
The ketogenic diet is a high-fat, moderate protein, low-carbohydrate diet that provides the brain with ketones for energy instead of glucose.
The earlier the patients start this treatment, the better the outcomes, like improvement in seizures, movement disorders, and learning ability.
In addition, occupational, physical, and speech & language therapies are often recommended for supporting optimal development in children and remains beneficial into adulthood.
New research shows more potential treatments for the future such as finding methods to enhance glucose transport; using supplemental oils and synthetic ketones to boost the effectiveness of or replace the ketogenic diet; and exploring a number of other options to better treat symptoms.
Finally, gene therapy, where the gene itself is fixed, might also be available in the future. Glut1 Deficiency should be considered and tested in any patient with suggestive symptoms.
If in doubt, “rule it out” A diagnosis and proper treatment is life changing for most patients. more information, please.
Visit the glute one deficiency Foundation website ww.w. G1b Foundation.
Org 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 other symptoms may include confusion lack of physical endurance.
attention deficits anxiety mood disturbances frequent headaches and sometimes characteristics along the autism spectrum However, not all patients experience all the symptoms especially in my other cases the range and combination of symptoms can vary from mild to severe sometimes making glued 1 deficiency difficult to diagnose.