This is a rare genetic disorder that impairs brain metabolism. GLUT1 (a protein) is responsible for the transport of glucose (a sugar) from the blood into the brain. Glucose is the main source of fuel for the brain. A shortage of glucose leads to impairment of brain function and growth.
SCL2A1 is the name of the gene that provides instructions to produce the protein, GLUT1. It is found on chromosome 1. Mutations (changes in the way the gene is made up or ‘sequenced’) in the SCL2A1 gene cause this condition. It is inherited in an autosomal dominant pattern. This means one copy of the altered gene in a cell is enough to cause the condition. However, most cases happen because of a new mutation in the gene. This means there will be no family history, although rarely one parent may be mildly affected.
Most children start having seizures in the first few months of life, although some children only develop seizures later, at around 2 to 4 years of age. Some children will never develop epilepsy, although this is very rare. They may also show other neurological symptoms including difficulties with balance and co-ordination and they may show abnormal movements of their limbs and eyes. The abnormal eye movements are more common in infants and young children but the abnormal limb movements usually occur throughout childhood.
Other names for GLUT1 deficiency syndrome
Glucose transporter type 1 deficiency syndrome
Children can have a variety of symptoms which can be present all the time, or can come and go (doctors describe these as ‘paroxysmal’ or ‘episodic’). Children with paroxysmal symptoms are often worse when they haven’t eaten much, or before a meal. Children may appear dazed, confused or ‘drunk’ when they wake up and before they have breakfast. The seizures may be of any type but are usually myoclonic (‘jerk’), atonic (‘drop’) and tonic-clonic. In this syndrome, abnormal paroxysmal eye movements may be noticed before the seizures start.
Babies with GLUT1 deficiency syndrome will often have slow head growth (called ‘microcephaly’) and developmental delay. They may go on to develop spasticity (stiffness of limbs) and abnormal posturing of limbs and/or trunk (dystonia). All of these features are more likely if the diagnosis is made late, particularly after 5 years of age.
Some older children have intermittent ataxia (imbalance), confusion, lethargy, hemiparesis (weakness on one side), total body paralysis, and movement disorders (called chorea or athetosis). These symptoms may fluctuate, and be influenced by fasting, exercise and/or fatigue. Children may have varying degrees of learning difficulties and speech delay.
A lumbar puncture (sometimes called a spinal tap) following a 4 to 6 hour period without food is the most helpful test. The concentration of glucose in the cerebrospinal fluid (CSF) is compared to the blood glucose level. If this ratio is less than 0.4, GLUT1 deficiency should be suspected. The level of lactate in the CSF is usually low.
Genetic testing could then be organised. This would find a mutation in the SLC2A1 gene in approximately 8 out of 10 cases.
The EEG may also be abnormal, but these abnormalities are not specific to this condition and do not help to make the diagnosis of GLUT1 deficiency.
Unfortunately, it is unlikely that any epilepsy medicines will ever fully control the seizures in children with this condition. For this reason, if epilepsy medicines are not controlling seizures in a young child with epilepsy, the condition should be thought about. The medicine phenobarbital, and caffeine, can both prevent glucose transport and worsen the seizures.
Although currently there is no cure, there is a special diet that can help, called the ketogenic diet. This is a low carbohydrate, high fat diet that mimics the state of starvation. The body makes ketones, which can be used by the brain as an alternative fuel to glucose. As soon as GLUT1 is diagnosed, the child should be offered treatment with the ketogenic diet. This is because it will help to improve the child’s seizures and abnormal movements. Many children will become seizure free. There is some evidence that the earlier the diagnosis happens and the earlier the ketogenic diet is started, the better the child’s development and learning.
The organisation Matthew’s Friends has more information about the ketogenic diet.
Information about treatments for children can be found on the Medicines for Children website.
There may also be research studies open that are relevant to this epilepsy syndrome. Your child’s doctor will be able to discuss this with you.
If your child has this syndrome they may have prolonged or repeated seizures. Your child’s doctor will discuss a ‘rescue’ or emergency care plan with you to treat any prolonged or repeated seizures.
The ketogenic diet is usually very effective in controlling the seizures, and may help improve the developmental outcome and learning. However, learning will not usually be completely normal. Children will often need epilepsy medicines as well and possibly treatment for any movement disorder. Children usually need support with their learning, feeding and physical difficulties.
The ketogenic diet will need to be given for many years and certainly throughout childhood and the teenage years, and possibly for life.
Charity specialising in medical ketogenic dietary therapies.
What is a syndrome?
A syndrome is a group of signs and symptoms that, added together, suggest a particular medical condition. In epilepsy, examples of these signs and symptoms would be things like the age at which seizures begin, the type of seizures, whether the child is male or female and whether they have physical or learning disabilities, or both. The results of an electroencephalogram (EEG) are also used to help identify epilepsy syndromes.
If you would like to know more about an epilepsy syndrome, please speak to your doctor. If you would like to know more about epilepsy in general, please contact Epilepsy Action.
Epilepsy Action would like to thank Dr Richard Appleton, consultant paediatric neurologist and honorary professor in paediatric neurology at Alder Hey Children’s Hospital, Liverpool, UK for preparing this information.