Exercise intolerance in Glycogen Storage Disease Type III: Weakness or energy deficiency?

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• 作者：Nicolai Preisler^a ; ^{npreisler@hotmail.com} ; Agnè ; s Pradel^b ; ^{agnes-francoise.pradel@psl.aphp.fr} ; Edith Husu^a ; ^{edithhusu@gmail.com} ; Karen Lindhardt Madsen^a ; ^{karen_lindhardt@hotmail.com} ; Marie-Hé ; lè ; ne Becquemin^c ; ^{marie-helene.becquemin@psl.aphp.fr} ; Alix Mollet^d ; ^{alix.mollet@abc.aphp.fr} ; Philippe Labrune^d ; ^e ; ^{philippe.labrune@abc.aphp.fr} ; Francois Petit^f ; ^{francois.petit@abc.aphp.fr} ; Jean-Yves Hogrel^g ; ^{jy.hogrel@institut-myologie.org} ; Claude Jardel^h ; ^{claude.jardel@psl.aphp.fr} ; Francois Maillotⁱ ; ^{maillot@med.univ-tours.fr} ; John Vissing^a ; ^{vissing@rh.dk} ; Pascal Laforê ; t^j ; ^{pascal.laforet@psl.aphp.fr}
• 关键词：GSD III ; Glycogen Storage Disease Type III ; GDE ; glycogen debranching enzyme ; VO2peak ; peak oxygen uptake ; Wpeak ; peak work rate ; RER ; respiratory exchange ratio ; RPE ; ratings of perceived exertion ; FFA ; free fatty acid ; PFK ; phosphofructokinase
• 刊名：Molecular Genetics and Metabolism
• 出版年：2013
• 出版时间：May, 2013
• 年：2013
• 卷：109
• 期：1
• 页码：14-20
• 全文大小：649 K

文摘

Myopathic symptoms in Glycogen Storage Disease Type IIIa (GSD IIIa) are generally ascribed to the muscle wasting that these patients suffer in adult life, but an inability to debranch glycogen likely also has an impact on muscle energy metabolism. We hypothesized that patients with GSD IIIa can experience exercise intolerance due to insufficient carbohydrate oxidation in skeletal muscle. Six patients aged 17-36-years were studied. We determined VO_2peak (peak oxygen consumption), the response to forearm exercise, and the metabolic and cardiovascular responses to cycle exercise at 70 % of VO_2peak with either a saline or a glucose infusion. VO_2peak was below normal. Glucose improved the work capacity by lowering the heart rate, and increasing the peak work rate by 30 % (108 W with glucose vs. 83 W with placebo, p = 0.018). The block in muscle glycogenolytic capacity, combined with the liver involvement caused exercise intolerance with dynamic skeletal muscle symptoms (excessive fatigue and muscle pain), and hypoglycemia in 4 subjects. In this study we combined anaerobic and aerobic exercise to systematically study skeletal muscle metabolism and exercise tolerance in patients with GSD IIIa. Exercise capacity was significantly reduced, and our results indicate that this was due to a block in muscle glycogenolytic capacity. Our findings suggest that the general classification of GSD III as a glycogenosis characterized by fixed symptoms related to muscle wasting should be modified to include dynamic exercise-related symptoms of muscle fatigue. A proportion of the skeletal muscle symptoms in GSD IIIa, i.e. weakness and fatigue, may be related to insufficient energy production in muscle.