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Movement disorders
Short report
Triheptanoin dramatically reduces paroxysmal motor disorder in patients with GLUT1 deficiency
  1. Fanny Mochel1,2,
  2. Elodie Hainque1,3,
  3. Domitille Gras1,4,
  4. Isaac M Adanyeguh1,
  5. Samantha Caillet5,
  6. Bénédicte Héron6,
  7. Agathe Roubertie7,8,
  8. Elsa Kaphan9,
  9. Romain Valabregue1,10,
  10. Daisy Rinaldi1,
  11. Sandrine Vuillaumier11,
  12. Raphael Schiffmann12,
  13. Chris Ottolenghi13,14,
  14. Jean-Yves Hogrel15,
  15. Laurent Servais16,
  16. Emmanuel Roze1,3
  1. 1Inserm 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
  2. 2Department of Genetics, AP-HP, Pitié-Salpêtrière University Hospital, Paris, France
  3. 3Department of Neurology, AP-HP, Pitié-Salpêtrière University Hospital, Paris, France
  4. 4Department of Neuropediatrics, AP-HP, Robert Debré University Hospital, Paris, France
  5. 5Department of Dietetics, AP-HP, Pitié-Salpêtrière University Hospital, Paris, France
  6. 6Department of Neuropediatrics, AP-HP, Armand Trousseau University Hospital, Paris, France
  7. 7Department of Neuropediatrics, Gui de Chauliac Hospital, Montpellier, France
  8. 8INSERM, U-1051, Institute of Neuroscience, Montpellier, France
  9. 9Department of Neurology, AP-HM, La Timone University Hospital, Marseille, France
  10. 10Center for NeuroImaging Research (CENIR), Institut du Cerveau et de la Moelle épinière, Paris, France
  11. 11Biochemistry and Genetic Laboratory, AP-HP, Bichat-Claude Bernard Hospital, Paris, France
  12. 12Baylor Research Institute, Institute of Metabolic Disease, Dallas, Texas, USA
  13. 13Metabolic Biochemistry Lab, AP-HP, Necker University Hospital, Paris, France
  14. 14University Paris Descartes, Paris, France
  15. 15Neuromuscular Physiology and Evaluation Lab, Institute of Myology, Paris, France
  16. 16Service of Clinical Research and Databases, Institute of Myology, Paris, France
  1. Correspondence to Dr Fanny Mochel, Institut du Cerveau et de la Moelle épinière, Aile 4A, Groupe Hospitalier Pitié-Salpétrière, Paris 75013, France; fanny.mochel{at}upmc.fr

Abstract

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.

  • METABOLIC DISEASE
  • MOVEMENT DISORDERS

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/jnnp-2015-311475

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