Around 90% of those affected have a form of the disorder often referred to as, 'common GLUT1 deficiency syndrome.' These people usually experience frequent seizures starting in the first months of their lives. In newborns, the first sign of the disorder may be involuntary eye movements that are rapid and irregular. Babies with common GLUT1 deficiency syndrome have an average head size at birth, yet growth of their brain and skull is often times slow, which may result in an abnormally small head size.
People with this form of GLUT1 deficiency syndrome might have developmental delay or intellectual disabilities. The majority of those affected also experience other neurological issues such as:
Approximately 10% of people with GLUT1 deficiency syndrome have a form of the disorder often known as, 'non-epileptic GLUT1 deficiency syndrome,' which is usually less severe than the more common form. People with the non-epileptic form do not experience seizures, but the might still have developmental delay and intellectual disabilities. The majority experience movement issues such as ataxia or dystonia. The movement issues may be more pronounced than in the common form.
Several conditions that were once given other names have since been recognized to be variants of GLUT1 deficiency syndrome. These conditions include:
GLUT1 deficiency syndrome is a rare disorder. Around 500 people with it have been reported around the world since the disorder was first identified in the year 1991. In Australia, the prevalence of the disorder has been estimated at 1 in 90,000 people. Researchers; however, suggest the disorder may be under-diagnosed because many neurological disorders can cause symptoms that are similar.
Genes Related to GLUT1 Deficiency Syndrome
GLUT1 deficiency syndrome is caused by mutations in the SLC2A1 gene. The gene provides instructions for producing a protein called the, 'Glucose Transporter Protein type 1 (GLUT1).' The GLUT1 protein is embedded in the outer membrane surrounding cells, where it transports a simple sugar called, 'glucose,' into cells from the person's blood, or from other cells for use as fuel.
In a person's brain, the GLUT1 protein is involved in moving glucose, which is the brain's main source of energy, across the blood-brain barrier. The blood-brain barrier acts as a boundary between tiny blood vessels and the surrounding brain tissue; it protects the brain's delicate nerve tissue by preventing several other types of molecules from entering the person's brain. The GLUT1 protein also moves glucose between cells in the brain called, 'glia,' which protect and maintain nerve cells.
SLC2A1 gene mutations reduce or even eliminate the function of the GLUT1 protein. Having less functional GLUT1 protein reduces the amount of glucose available to the person's brain cells, which affects their brain development and function.
Inheriting GLUT1 Deficiency Syndrome
GLUT1 deficiency syndrome is usually inherited in an autosomal dominant pattern, meaning one copy of the altered gene in each cell is sufficient to cause the disorder. Around 90% of instances of GLUT1 deficiency syndrome result from new mutations in the gene. These instances happen in people with no history of the disorder in their families. In other instances, an affected person inherits the mutation from an affected parent.
In a small number of families, GLUT1 deficiency syndrome is inherited in an autosomal recessive pattern, meaning both copies of the gene in each cell have mutations. The parents of a person with an autosomal recessive condition each carry one copy of the mutated gene, yet they usually do not experience signs and symptoms of the condition.
Symptoms of GLUT1 Deficiency Syndrome
There are many symptoms of GLUT1 deficiency syndrome and they vary in degree. Most often, an infant or child presents with unexplainable seizures. Doctors rule out the usual causes and find themselves unable to determine why the child's seizures persist. People with GLUT1 usually do not respond to anti-seizure medications. In fact - the gold standard for pediatric seizures, phenylbarbitol, actually inhibits glucose transport to the brain! So, infants and children who are administered this medication usually get even worse from a symptoms perspective. Along with seizures, other symptoms of GLUT1 include low muscle tone, which leads to physical difficulties to include problems with:
As well as many other usual childhood physical activities. All children with GLUT1 deficiency syndrome experience issues with speech - both receptive and expressive. What this means is they may not be able to speak at all, or they may have slurred speech, or difficult accessing and articulating sounds, words and sentences. They might also experience cognitive and learning delays and disabilities. If their brains do not receive enough energy for brain growth, microcephaly occurs.
Treating GLUT1 Deficiency Syndrome
The only known type of treatment to date is a highly restrictive diet called the, 'Ketogenic Diet,' which is usually used for children with seizure disorders who do not benefit from conventional medications. It is a treatment of last resort. For children with this syndrome it is the only treatment that might help to control the seizures and hopefully help with providing energy to their brains. What remains unknown; however, is how effective this type of treatment might be.
The Ketogenic Diet
The ketogenic diet is a very restrictive, high fat and calorie-limited diet. All food the person consumes is based on a ratio of fat to protein and carbohydrate combined, usually a 4:1 or 3:1 ratio such as 3 or 4 grams of fat to 1 gram of protein and carbohydrate combined. No sugar is allowed and minimal carbohydrate is included. Every meal or snack is measured in grams and usually includes a small amount of protein, a tiny amount of a lower carbohydrate fruit or vegetable and a large amount of oil, mayonnaise, butter, or heavy cream as a fat source. The diet is so precise and restrictive that children on it must avoid even topical ingredients that might have sugar sources or carbohydrates, such as toothpaste, medications, sunscreen, or lotion.
Strict compliance with the diet causes a person's body to produce, 'ketones.' Ketones are used by a person's brain as an alternative fuel source. The ketogenic diet usually helps with controlling seizures. It is currently not known how much this diet may benefit other symptoms of GLUT1 deficiency syndrome.
Every child on this diet has to be monitored to measure for adequate ketones. The best way to measure ketones is with a blood monitoring machine that requires sticking a child's finger. If ketones are too low, the child might have seizures or other symptoms of GLUT1 deficiency syndrome. If ketones are too high - acidosis or other side-effects may occur.
The ketogenic diet does not provide adequate nutrition. Children on this diet take different daily supplements to attempt to keep their bodies appropriately nourished and growing. Their blood, organs and bodies are carefully monitored by doctors to watch for and try to prevent possible issues caused by the diet. Some side-effects that may occur while on this diet include high cholesterol, kidney stones, slow growth or weight gain, dehydration and bone fractures. The long-term effects of the ketogenic diet on a person's body remain unknown.
GLUT-1 Deficiency Syndrome
The Child Brain Foundation
Glut1 Deficiency Foundation