Children with severe epilepsy who do not respond to traditional drugs could be treated with vitamin B6, after the discovery of a new gene by UCL Great Ormond Street Institute of Child Health (ICH) and its clinical partner Great Ormond Street Hospital (GOSH).
The gene, proline synthetase co-transcribed homolog (bacterial) (PROSC), was identified as being faulty in children with a rare strain of vitamin B6-dependent epilepsy, where patients do not respond to standard anti-epilepsy drugs (AED).
In such cases, children are currently left to struggle with the debilitating effects of untreated epilepsy such as regular seizures, damage to the brain, severe disabilities and in some cases death.
But after treatment with vitamin B6, the patients in the study who had the defective gene experienced a dramatic reduction in seizures, reducing their risk of incurring severe damage to the brain.
The finding builds on existing research by the GOSH-ICH team who have previously uncovered two other defective genes. Together, the discoveries hold the key for better diagnosis and treatment for hundreds of young patients with epilepsy.
Research co-lead Dr Philippa Mills, Lecturer in Genetics and Genomic Medicine at the UCL GOS Institute of Child Health, said: “Frequent, severe seizures can be dangerous and gruelling for children and families.
“This discovery provides us with a gene to test that can conclusively diagnose epilepsy that will improve with vitamin B6. For these patients vitamin B6 can literally be a lifesaver.”
Professor David Goldblatt, Director of Research and Development, Great Ormond Street Hospital: “This finding emphasises the importance of looking for new genes responsible for epilepsy, as it opens up new therapeutic options for patients. This is an integral part of our research strategy.
“Here at GOSH and the ICH we are committed to continuing with genetic research such as this so that we can continue to provide innovative and lifesaving treatments to children across the UK, and indeed further afield.”
The research team, led by Professor Peter Clayton and Dr Philippa Mills, identified a gene called proline synthetase co-transcribed homolog (bacterial) (PROSC) which, when defective, caused epilepsy in seven patients who did not respond to traditional anti-epilepsy drugs.
Genetic screening for other forms vitamin B6-dependent epilepsy already exists thanks to previous work carried out at Great Ormond Street Hospital and the UCL Great Ormond Street Institute of Child Health. This new gene will now be added to the list of genes that can be searched for.
Children with vitamin B6-dependent epilepsy require more vitamin B6 than most children. The absence of the additional vitamin B6 manifests as AED resistant epilepsy.
This project is supported by Great Ormond Street Hospital Children’s Charity and is one of over 1000 being carried out at Great Ormond Street Hospital and the UCL Great Ormond Street Institute of Child Health as part of their paediatric research programme.
GOSH patient Scarlett, 7, has vitamin B6-dependent epilepsy. She received her full diagnosis after a GOSH research team discovered she had a faulty gene, ALDH7A1, the second defective gene to be uncovered in the course of their research. Since commencing the vitamin treatment Scarlett’s seizures have stopped entirely.
After she was born Scarlett started to have seizures several times a week. The fits were difficult to control and so severe that Scarlett was frequently admitted to hospital, with several admissions spent on intensive care. She was referred to GOSH due to the complexity of her condition. Without treatment the seizures were causing delays in Scarlett’s development.
When she was six-months-old, new genetic screening finally established a faulty gene was causing vitamin B6-dependent epilepsy. Scarlett’s father Ben explains: “Once doctors knew vitamin B6 could help, the transformation was immediate. The seizures stopped, and she hasn’t had a single fit in five years.”
“There were several times when we didn’t think Scarlett would make it, but she is now running around enjoying all the things a little girl her age should.”
Ben says: “Genetic research provided the answers for Scarlett. Without vital funding, researchers wouldn’t have been able to make this breakthrough and Scarlett might not be here today.”
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Notes to Editors
“Mutations in PROSC Disrupt Cellular Pyridoxal Phosphate Homeostasis and Cause Vitamin B6-Dependent Epilepsy” will be published in The American Journal of Human Genetics.
Great Ormond Street Hospital for Children NHS Trust is the country’s leading centre for treating sick children, with the widest range of specialists under one roof.
With the UCL Great Ormond Street Institute of Child Health, we are the largest centre for paediatric research outside the US and play a key role in training children’s health specialists for the future.
Great Ormond Street Hospital Children’s Charity needs to raise money to support the hospital to give children who need help the most the best chance for life. The charity funds patient and family support programmes, provides the latest medical equipment and supports the essential redevelopment of the hospital. It has also launched a five-year strategy to support research in some of the most serious and complex childhood diseases. Great Ormond Street Hospital Children’s Charity is the largest dedicated funder of paediatric research in the UK and our work is entirely funded through the generosity of supporter donations. For more information visit www.gosh.org