Favourable response to ketogenic dietary therapies: undiagnosed glucose 1 transporter deficiency syndrome is only one factor.
OBJECTIVE
We aimed to determine whether response to ketogenic dietary therapies (KDT) was due to undiagnosed glucose transporter type 1 deficiency syndrome (GLUT1-DS).


METHODS
Targeted resequencing of the SLC2A1 gene was completed in individuals without previously known GLUT1-DS who received KDT for their epilepsy. Hospital records were used to obtain demographic and clinical data. Response to KDT at various follow-up points was defined as seizure reduction of at least 50%. Seizure freedom achieved at any follow-up point was also documented. Fisher's exact and gene-burden association tests were conducted using the PLINK/SEQ open-source genetics library.


RESULTS
Of the 246 participants, one was shown to have a novel variant in SLC2A1 that was predicted to be deleterious. This individual was seizure-free on KDT. Rates of seizure freedom in cases without GLUT1-DS were below 8% at each follow-up point. Two cases without SLC2A1 mutations were seizure-free at every follow-up point recorded. No significant results were obtained from Fisher's exact or gene-burden association tests.


CONCLUSIONS
A favourable response to KDT is not solely explained by mutations in SLC2A1. Other genetic factors should be sought to identify those who are most likely to benefit from dietary treatment for epilepsy, particularly those who may achieve seizure freedom.
NIHR University College London Hospitals Biomedical Research Centre, UCL Institute of Neurology, London, UK.|UCL Institute of Child Health, London, UK.
Natasha E
NE
Schoeler
UCL Institute of Child Health, London, UK.|Young Epilepsy, Lingfield, UK.|Great Ormond Street Hospital for Children, London, UK.
Judith Helen
JH
Cross
NE Thames Regional Genetics Service, Great Ormond Street Hospital for Children, London, UK.
Suzanne
S
Drury
NE Thames Regional Genetics Service, Great Ormond Street Hospital for Children, London, UK.|Congenica Ltd, Cambridge, UK.
Nicholas
N
Lench
Epilepsy Research Centre, The University of Melbourne, Austin Health, Melbourne, Vic., Australia.
Jacinta M
JM
McMahon
Royal Children's Hospital, Melbourne, Vic., Australia.|Murdoch Children's Research Institute, Melbourne, Vic., Australia.
Mark T
MT
MacKay
Royal Children's Hospital, Melbourne, Vic., Australia.|Departments of Medicine and Paediatrics, The University of Melbourne, Austin Health, Melbourne, Vic., Australia.
Ingrid E
IE
Scheffer
NIHR University College London Hospitals Biomedical Research Centre, UCL Institute of Neurology, London, UK.|Sichting Epilepsie Instellingen Nederland (SEIN), Heemstede, the Netherlands.|Epilepsy Society, Chalfont, St. Peter, UK.
Josemir W
JW
Sander
NIHR University College London Hospitals Biomedical Research Centre, UCL Institute of Neurology, London, UK.|Epilepsy Society, Chalfont, St. Peter, UK.
Sanjay M
SM
Sisodiya
D002239:Carbohydrate Metabolism, Inborn Errors / Q000175:diagnosis / Q000178:diet therapy* / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D055423:Diet, Ketogenic; D004827:Epilepsy / Q000178:diet therapy* / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D060005:Genotyping Techniques; D051272:Glucose Transporter Type 1 / Q000235:genetics*; D006801:Humans; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000172:deficiency* / Q000235:genetics; D012640:Seizures / Q000178:diet therapy / Q000235:genetics / Q000503:physiopathology; D016896:Treatment Outcome
D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; C495677:SLC2A1 protein, human