• Fanny Mochel, Elodie Hainque, Domitille Gras, Isaac M Adanyeguh, Samantha Caillet, Bénédicte Héron, Agathe Roubertie, Elsa Kaphan, Romain Valabregue, Daisy Rinaldi, Sandrine Vuillaumier, Raphael Schiffmann, Chris Ottolenghi, Jean-Yves Hogrel, Laurent Servais, and Emmanuel Roze.
• Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France Department of Genetics, AP-HP, Pitié-Salpêtrière University Hospital, Paris, France.
• J. Neurol. Neurosurg. Psychiatr. 2016 May 1; 87 (5): 550-3.

ObjectiveOn the basis of our previous work with triheptanoin, which provides key substrates to the Krebs cycle in the brain, we wished to assess its therapeutic effect in patients with glucose transporter type 1 deficiency syndrome (GLUT1-DS) who objected to or did not tolerate ketogenic diets.MethodsWe performed an open-label pilot study with three phases of 2 months each (baseline, treatment and withdrawal) in eight patients with GLUT1-DS (7-47 years old) with non-epileptic paroxysmal manifestations. We used a comprehensive patient diary to record motor and non-motor paroxysmal events. Functional (31)P-NMR spectroscopy was performed to quantify phosphocreatine (PCr) and inorganic phosphate (Pi) within the occipital cortex during (activation) and after (recovery) a visual stimulus.ResultsPatients with GLUT1-DS experienced a mean of 30.8 (± 27.7) paroxysmal manifestations (52% motor events) at baseline that dropped to 2.8 (± 2.9, 76% motor events) during the treatment phase (p = 0.028). After withdrawal, paroxysmal manifestations recurred with a mean of 24.2 (± 21.9, 52% motor events; p = 0.043). Furthermore, brain energy metabolism normalised with triheptanoin, that is, increased Pi/PCr ratio during brain activation compared to the recovery phase (p = 0.021), and deteriorated when triheptanoin was withdrawn.ConclusionsTreatment with triheptanoin resulted in a 90% clinical improvement in non-epileptic paroxysmal manifestations and a normalised brain bioenergetics profile in patients with GLUT1-DS.Trial Registration NumberNCT02014883.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

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