RT Journal Article
SR Electronic
T1 Triheptanoin dramatically reduces paroxysmal motor disorder in patients with GLUT1 deficiency
JF Journal of Neurology, Neurosurgery & Psychiatry
JO J Neurol Neurosurg Psychiatry
FD BMJ Publishing Group Ltd
SP 550
OP 553
DO 10.1136/jnnp-2015-311475
VO 87
IS 5
A1 Fanny Mochel
A1 Elodie Hainque
A1 Domitille Gras
A1 Isaac M Adanyeguh
A1 Samantha Caillet
A1 Bénédicte Héron
A1 Agathe Roubertie
A1 Elsa Kaphan
A1 Romain Valabregue
A1 Daisy Rinaldi
A1 Sandrine Vuillaumier
A1 Raphael Schiffmann
A1 Chris Ottolenghi
A1 Jean-Yves Hogrel
A1 Laurent Servais
A1 Emmanuel Roze
YR 2016
UL http://jnnp.bmj.com/content/87/5/550.abstract
AB Objective On 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.Methods We 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 31P-NMR spectroscopy was performed to quantify phosphocreatine (PCr) and inorganic phosphate (Pi) within the occipital cortex during (activation) and after (recovery) a visual stimulus.Results Patients 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Pi/PCr ratio during brain activation compared to the recovery phase (p=0.021), and deteriorated when triheptanoin was withdrawn.Conclusions Treatment with triheptanoin resulted in a 90% clinical improvement in non-epileptic paroxysmal manifestations and a normalised brain bioenergetics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 number NCT02014883.