Investigating glycogenosis type III patients with multi-parametric functional NMR imaging and spectroscopy

Wary, Claire; Nadaj-Pakleza, Aleksandra; Laforêt, Pascal; Claeys, Kristl G.; Carlier, Robert; Monnet, Aurélien; Fleury, Servanne; Baligand, Céline; Eymard, Bruno; Labrune, Philippe; Carlier, Pierre G.

doi:10.1016/j.nmd.2010.06.011

« Previous Next »Neuromuscular Disorders
Volume 20, Issue 8 , Pages 548-558, August 2010

Investigating glycogenosis type III patients with multi-parametric functional NMR imaging and spectroscopy

Claire Wary
- Institute of Myology, Paris, France
- CEA, I²BM, MIRCen, IdM NMR Laboratory, Paris, France
- UPMC University Paris 06, Paris, France
- Corresponding author. Address: NMR Laboratory AIM-CEA, Institut de Myologie, Bat Babinski, G.H. Pitie-Salpetriere, 75651 Paris Cedex 13, France. Tel.: +33 1 42 16 58 92; fax: +33 1 42 16 58 97.
Aleksandra Nadaj-Pakleza
- East-Paris Reference Center for Neuromuscular Pathology, Pitié-Salpêtrière University Hospital, AP-HP, Paris, France
- Department of Neurology, Angers University Hospital, Angers, France
Pascal Laforêt
- Institute of Myology, Paris, France
- East-Paris Reference Center for Neuromuscular Pathology, Pitié-Salpêtrière University Hospital, AP-HP, Paris, France
Kristl G. Claeys
- Institute of Myology, Paris, France
- East-Paris Reference Center for Neuromuscular Pathology, Pitié-Salpêtrière University Hospital, AP-HP, Paris, France
Robert Carlier
- Institute of Myology, Paris, France
- Medical Imaging Department and Center for Technological Innovation, Raymond Poincaré University Hospital, AP-HP, Garches, France
Aurélien Monnet
- Institute of Myology, Paris, France
- CEA, I²BM, MIRCen, IdM NMR Laboratory, Paris, France
- UPMC University Paris 06, Paris, France
Servanne Fleury
- Institute of Myology, Paris, France
- CEA, I²BM, MIRCen, IdM NMR Laboratory, Paris, France
- UPMC University Paris 06, Paris, France
Céline Baligand
- Institute of Myology, Paris, France
- CEA, I²BM, MIRCen, IdM NMR Laboratory, Paris, France
- UPMC University Paris 06, Paris, France
Bruno Eymard
- Institute of Myology, Paris, France
- East-Paris Reference Center for Neuromuscular Pathology, Pitié-Salpêtrière University Hospital, AP-HP, Paris, France
Philippe Labrune
- Department of Pediatrics, Antoine Béclère University Hospital, AP-HP, Clamart, France
Pierre G. Carlier
- Institute of Myology, Paris, France
- CEA, I²BM, MIRCen, IdM NMR Laboratory, Paris, France
- UPMC University Paris 06, Paris, France

Received 23 February 2010; received in revised form 27 May 2010; accepted 7 June 2010.

Abstract

Debranching enzyme deficiency (Glycogen storage disease (GSD) type III) causes progressive muscle wasting myopathy. A comprehensive nuclear magnetic resonance study involving spectroscopy (NMRS) and imaging (NMRI) evaluated status and function of calf muscles in 18 GSDIII patients. At rest, ³¹P NMRS showed elevated pH and accumulation of anomalous phosphomonoesters, ¹³C NMRS quantified excess glycogen accumulation and NMRI demonstrated progressive fat replacement that paralleled muscle weakness. Multi-parametric functional NMR, performed at recovery from a single bout of aerobic exercise, simultaneously assessed oxidative phosphorylation from ³¹P NMRS, muscle perfusion and BOLD, a marker of blood oxygenation, from arterial spin labeled NMRI, and oxygen uptake from deoxymyoglobin proton NMRS. While blocked glycogenolysis caused inadequate substrate supply to the mitochondria, combined measurements suggested that altered perfusion was also responsible for impaired post-exercise phosphocreatine recovery and could contribute to exercise intolerance in GSDIII. These non-invasive investigations provide new indices to quantify the progression of GSDIII.

Keywords: Glycogen storage disease, Debranching enzyme, Myopathy, Muscle function, Perfusion, BOLD, Glycogen, NMR, Spectroscopy, Imaging