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18 May 2015

Genetic research increases understanding of ketogenic diet

A new study has highlighted the need to explore further genetic factors which may increase our understanding of why some people with epilepsy respond to ketogenic diet therapies while others don't.

Ketogenic diet therapies are high in fat and low in carbohydrate and switch the body's energy fuels from glucose to 'ketone bodies'. This is particularly beneficial for those with glucose transporter type-1 deficiency syndrome (GLUT1-DS) where glucose is unable to cross the blood-brain barrier into the brain. This deficiency is caused by mutations in the gene SLC2A1.

Reports have shown that people with mutations in this gene tend to have a more favourable response to the ketogenic diet therapies with some achieving complete seizure freedom. Only rarely do people without mutations in SLC2A1 achieve seizure freedom although they may see a significant reduction in seizure frequency of 50 per cent or more.

Epilepsy Society leads research

Now, however, the latest study led by Epilepsy Society's geneticist Professor Sanjay Sisodiya, has shown that mutations in the gene SLC2A1 may not be the only explanation for a positive response to the ketogenic diet therapies.

Working with researchers from the UK, Netherlands and Australia, he has shown that there are other genetic factors involved which may help to predict who is likely to benefit from ketogenic diet therapy treatment.

The research team set out to discover whether people without GLUT1-DS who achieve seizure freedom on ketogenic diet therapies, may in fact have undiagnosed GLUT1-DS. They looked at 246 individuals who were following a ketogenic diet therapy but who had not been diagnosed with the syndrome. Their seizure frequency was recorded at regular intervals over a period of up to 24 months and researchers looked at the gene SLC2A1 in each individual.

Results showed that after three months, more than half of participants had a 50 per cent or more reduction in seizure frequency while nine of them (four per cent) were seizure free. The majority of these participants were children.

Genetic factors in response to ketogenic diet

The number of participants remaining on ketogenic diet therapies fell during each interval. At 12 months, 89 of 111 people (80 per cent) had a 50 per cent or more reduced seizure frequency with seven (six per cent) seizure free: at 24 months, 37 out of 46 people (80 per cent) had an equivalent reduced seizure frequency and three (seven per cent) were seizure-free.

Out of all the 246 participants, three people were found to be seizure-free at every interval, but only one had an SLC2A1 mutation thought to be undiagnosed GLUT1-DS. The other two people achieved seizure freedom at every interval although they had no mutations in the gene SLC2A1, suggesting other genetic factors may be involved. All three were weaned off their anti-epileptic medication.

Professor Sanjay Sisodiya commented: 'Although the percentage of people achieving seizure freedom without mutations in SLC2A1 is less than eight per cent, our study shows that a favourable response to ketogenic diet therapies cannot be solely explained by this gene. It highlights the need to find other genetic factors so that we can identify those who are most likely to benefit from these diets, particularly those who may achieve seizure freedom.'