GLUT1 Deficiency Syndrome

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GLUT 1 deficiency syndrome is an inherited metabolic disorder that is caused by a fault in the SCL2A1 gene. This gene is responsible for making a protein called Glucose Transporter type 1 (GLUT 1). The GLUT1 protein is needed to transport glucose from the blood into the brain. Glucose is the main source of energy for the brain. A fault in the SCL2A1 gene causes the body to make an insufficient amount of the GLUT1 protein and this means the brain cannot receive an adequate amount of glucose.

GLUT 1 deficiency syndrome is a rare metabolic disorder, approximately 500 cases have been reported worldwide since it was first discovered in 1991. It is estimated that it may occur in just under 3 people per one million. However, it is possible that it is under-recognised due to variability in clinical signs and symptoms. There have been no reports of a higher risk between males and females or ethnicities. It is estimated that there may be over 150 cases in the UK.

Signs and symptoms of this metabolic condition include:

• Recurrent seizures which appear in the first few months of life (accounting for over 80% of patients). These often tend to be resistant (refractory) to usual anti epilepsy medications. Patients can have different types of seizures but absences, myoclonic seizures and generalised tonic clonic seizures are common.
• Developmental delay
• Small head size (acquitted microcephaly)
• Behavioural problems
• Intellectual disability
• Ataxia (difficulty controlling muscle coordination)
• Movement disorders: these can consist of abnormal muscle spasms, stiffness, or writhing type movements (choreathetosis). These can occur in episodes triggered by exertion or spontaneously. This is called paroxysmal dyskinesia or paroxysmal choreoathetosis
• Speech and language impairment
• Anxiety
• Migraines.

Symptoms of this condition can worsen with fasting, especially prior to breakfast. Illness can cause symptoms to be temporarily worse.

Other signs of this disorder may include recurrent headaches, confusion, and lack of energy.

Most children develop seizures in the first few months of life however, some can develop them around the age of 2-4 years of age and small proportion of patients do not develop epilepsy but may have only episodic movement disorder.

Signs and symptoms are often helpful to suspect GLUT 1 deficiency syndrome however, a definitive diagnosis needs to be established by lumbar puncture (sometimes referred to as a spinal tap) and genetic testing. Lumbar puncture involves obtaining a sample of the fluid surrounding the brain and spinal cord (cerebrospinal fluid/CSF) to check the levels of glucose and compare that against levels in the blood. This procedure is performed after a 6-hour fasting period.

Genetic testing needs to be undertaken to confirm evidence of the gene mutation in GLUT1 gene. (SLC2A1). This requires a sample of blood to obtain DNA and analyse it.

A red blood cell glucose uptake assay can be performed to diagnose GLUT-1 deficiency syndrome. However, this test is now not done routinely due to easier availability of genetic testing.

There is no absolute cure for GLUT1 deficiency syndrome. As not enough glucose is getting to the brain, an alternative source of energy must be supplied to the brain for it to function. Hence, this condition is usually managed by prescribing a ketogenic diet which is the only recommended and effective treatment at present.

A ketogenic diet consists of foods that are high in fat and low in carbohydrate. It is a medically prescribed diet and must be undertaken with adequate dietetic supervision and support and involvement of clinicians. Typical foods high in fat are those such as butter, cream, avocado, coconut oil, red meat, and oils from nuts and fish etc. Ketones are biochemical substances produced when fat is utilised by the body for energy generation. These provide an alternative energy source for the brain and body when it cannot access glucose as is the case in this condition.

The ketogenic diet is very effective in controlling seizures in this condition and most people with paroxysmal movement disorder (intermittently occurring involuntary movements) also obtain benefit from this. Earlier diagnosis is very important as the introduction of the diet as soon as possible when the child’s brain is growing rapidly is extremely important to optimise outcome.

Alongside dietary treatment, it is also important to avoid medications that can adversely affect glucose transport such as phenobarbitone, caffeine, diazepam etc.

Most GLUT1 deficiency syndrome cases arise due to new mutations in GLUT1 gene in an individual. A small proportion may be inherited by having a copy of the faulty gene inherited from a parent (autosomal dominant inheritance) Sometimes, manifestations in parents may be very mild and thus there is a lot of variability in clinical features even if the inherited gene change is the same. If you have a child affected by GLUT1 deficiency syndrome, your blood can be tested to see if this has arisen in the child as a new or inherited genetic fault.

Once you have received a diagnosis, you can speak to a genetic counsellor who can explain how you may have inherited GLUT 1 deficiency syndrome and whether future children will be affected by this condition.

If you have previously had a child with GLUT 1 deficiency syndrome and go on to have further children, genetic testing can be undertaken in the newborn baby urgently to diagnose before they develop symptoms especially if you carry the faulty gene.

Thank you to Glut1 Deficiency UK for helping provide this up-to-date information.

Glut1 Deficiency UK aims to improve the lives of those in the Glut1 Deficiency community through increasing awareness, improving education of families and healthcare professionals, advocating for families and patients and supporting and funding Glut1 Deficiency research.

Contact Details:

• Email hello@glut1deficiency.org.uk
• Website https://www.g1dfoundation.org/

References are available on request. Please contact us by phoning 0845 241 2173 or emailing contact@metabolicsupportuk.org [Resource Library No:] GCM003