GLUT1 deficiency syndrome

Glucose is the brain's main source of energy. The GLUT1 protein, made from the SLC2A1 gene, carries glucose from the blood into the brain across the blood-brain barrier and between brain cells. In GLUT1 deficiency syndrome there is not enough working protein, so the brain does not receive adequate glucose, which affects its growth and function.

The condition was first described in 1991 and roughly 500 cases had been reported worldwide at the time of the Metabolic Support UK summary, which suggests there may be more than 150 people in the UK. Specialists believe it is under-recognised because the features resemble many other neurological disorders. Scottish data cited by MedlinePlus estimate an incidence of 1 in 24,000 newborns.

About 90 per cent of affected people have the common form, with frequent seizures starting in the first months of life. In newborns a first sign can be rapid, irregular eye movements. Head size is normal at birth but brain and skull growth may be slow, leading to a small head. Seizure types include absences, myoclonic seizures and generalised tonic-clonic seizures, and they often tend to be resistant to usual medicines.

Others have a non-epileptic form, around 10 per cent, with no seizures but developmental delay and movement problems such as unsteadiness or involuntary muscle tensing that may be more prominent than in the common form. Some children develop seizures later, at around 2 to 4 years.

• Poor coordination (ataxia) and episodes of muscle spasm, stiffness or writhing movements (paroxysmal dyskinesia), sometimes brought on by exertion.

• Speech and language difficulty, headaches, confusion and low energy.

• Symptoms that worsen with fasting, especially before breakfast, and that can temporarily worsen with illness.

Features raise suspicion, but a definite diagnosis rests on two tests. A lumbar puncture takes a sample of the fluid around the brain and spinal cord, to compare its glucose with the glucose in blood, after a 6-hour fast. A low spinal fluid glucose with normal blood glucose is the key finding. Genetic testing on a blood sample then looks for a change in SLC2A1.

A red blood cell glucose uptake test exists but is no longer done routinely because genetic testing is easier to obtain. Early referral to a paediatric neurologist matters, because anyone with infant-onset epilepsy that does not respond to treatment should be considered for this diagnosis.

There is no cure. Because not enough glucose reaches the brain, an alternative fuel is needed. The ketogenic diet is high in fat and low in carbohydrate, which makes the body produce ketones that the brain can use instead of glucose. Metabolic Support UK describes it as the only recommended and effective treatment at present and says it controls seizures very well and benefits most people with paroxysmal movement disorder.

It is a medical diet and must be run by a specialist dietitian with a clinician. Earlier diagnosis is very important because starting the diet when the brain is growing fastest gives the best chance of a good outcome. Parents learn to measure and prepare food, check ketones and manage illness, school meals and holidays.

Some medicines can interfere with glucose transport and are best avoided, including phenobarbitone, caffeine and diazepam, so every prescriber and school nurse should know the diagnosis.

Most cases are caused by a new gene change in the individual, not inherited. A smaller number inherit the change from a parent in an autosomal dominant pattern, and a parent may have only mild features. Testing a parent's blood can show whether the change was new. A genetic counsellor can explain the risk for future children.

Glut1 Deficiency UK is a registered charity that raises awareness, supports families and funds research. NHS care is delivered by paediatric neurology and dietetic teams, often in specialist centres, with adult neurology and metabolic services taking over later. Families can ask their specialist team how ketogenic diet support is organised locally.

Call 999 for a seizure that lasts longer than the time written in the care plan, repeated seizures without recovery, or breathing difficulty. Seek same-day advice for vomiting that stops a child eating on the ketogenic diet, as illness can unbalance ketosis.