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Glucose transporter type 1 deficiency syndrome (GLUT1-DS) causes cerebral energy deficiency due to altered transport of glucose across the blood brain barrier and into astrocytes.1 Its main phenotype combines developmental delay, permanent motor dysfunction and paroxysmal neurological manifestations.1 In addition, GLUT1-DS may solely consist of paroxysmal manifestations such as seizures or exercise-induced paroxysmal dyskinesia.
Ketogenic diet is the primary treatment of GLUT1-DS with clear efficacy on seizures and non-epileptic motor manifestations,1 but it has severe constraints. Ketogenic diet failure has been occasionally reported due to poor tolerance, inefficacy or failure to achieve ketosis,2 emphasising the need for alternative therapeutic options. Triheptanoin is a triglyceride containing three 7-carbon fatty acids, which provides acetyl-coenzyme A (CoA) and propionyl-CoA, two key carbon sources for the Krebs cycle.3 Treatment with triheptanoin resulted in a dramatic and sustained reduction of non-epileptic paroxysmal events in a group of GLUT1-DS patients who were not on ketogenic diet.4 5 Here, we evaluated the long-term effect of triheptanoin in four GLUT1-DS patients with persistent paroxysmal manifestations while on ketogenic diet.
Material and methods
We enrolled four GLUT1-DS patients (table 1) who reported persistent paroxysmal events while on ketogenic diet (trial registration number NCT02014883). Three adults and one child’s legal guardian signed a written informed consent for participation in this study sponsored by INSERM.
The study was divided into baseline, transition from ketogenic diet to triheptanoin (transition), short-term evolution (short term) and long-term follow-up (long term) with triheptanoin. A flow …
Contributors EH, AM, ER and FM drafted the manuscript for content. FM designed the study. EH, DG, M-PL, MA, MB, CO and FM acquired data. EH and FM analysed/interpreted data. EH performed the statistical analysis.
Funding Ultragenyx Pharmaceutical Inc. provided the investigational drug triheptanoin and funded the study. The research leading to these results has received funding from the programme ‘Investissements d’avenir’ ANR-10-IAIHU-06.
Competing interests FM has a patent on the use of triheptanoin in GLUT1-DS (WO2014093901), which has been issued. AM reports non-financial support from ABBVIE, outside the submitted work. ER reports grants, personal fees and non-financial support from Orkyn, grants, personal fees and non-financial support from Aguettant, grants, personal fees and non-financial support from Merz pharma, grants from Ipsen, personal fees from Medday pharma, personal fees from Retrophin, grants and non-financial support from Elivie, grants from Fondation Desmarest, grants from Fonds de dotation Brou de Laurière, grants from Agence Nationale de la Recherche, grants from AMADYS, grants, personal fees and non-financial support from Everpharma, personal fees and non-financial support from Movement Disorders Society, personal fees from European Academy of Neurology, personal fees from International Association of Parkinsonism and related Disorders, non-financial support from Merck, non-financial support from Dystonia Coalition, non-financial support from Dystonia Medical Research Foundation, outside the submitted work.
Patient consent for publication Not required.
Ethics approval Patients and child’s legal guardian signed a written informed consent for participation in this study sponsored by INSERM and approved by the local ethical committee (ID RCB: 2013-A01300-45).
Provenance and peer review Not commissioned; externally peer reviewed.
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