Nicolai Preisler1, Pascal Laforêt2, Karen Lindhardt Madsen3, Edith Husu3, Christoffer Rasmus Vissing3, Gitte Hedermann3, Henrik Galbo4, Christopher Lindberg5, John Vissing3. 1. Copenhagen Neuromuscular CenterDepartment of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark npreisler@hotmail.com. 2. Centre de Référence de Pathologie Neuromusculaire Paris-EstInstitut de Myologie, GH Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France. 3. Copenhagen Neuromuscular CenterDepartment of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 4. Department of Inflammation ResearchRigshospitalet, Copenhagen, Denmark. 5. Department of NeurologySahlgrenska University Hospital, Gothenburg, Sweden.
Abstract
OBJECTIVE: Pompe disease (glycogenosis type II) is caused by lysosomal alpha-glucosidase deficiency, which leads to a block in intra-lysosomal glycogen breakdown. In spite of enzyme replacement therapy, Pompe disease continues to be a progressive metabolic myopathy. Considering the health benefits of exercise, it is important in Pompe disease to acquire more information about muscle substrate use during exercise. METHODS: Seven adults with Pompe disease were matched to a healthy control group (1:1). We determined (1) peak oxidative capacity (VO2peak) and (2) carbohydrate and fatty acid metabolism during submaximal exercise (33 W) for 1 h, using cycle-ergometer exercise, indirect calorimetry and stable isotopes. RESULTS: In the patients, VO2peak was less than half of average control values; mean difference -1659 mL/min (CI: -2450 to -867, P = 0.001). However, the respiratory exchange ratio increased to >1.0 and lactate levels rose 5-fold in the patients, indicating significant glycolytic flux. In line with this, during submaximal exercise, the rates of oxidation (ROX) of carbohydrates and palmitate were similar between patients and controls (mean difference 0.226 g/min (CI: 0.611 to -0.078, P = 0.318) and mean difference 0.016 µmol/kg/min (CI: 1.287 to -1.255, P = 0.710), respectively). CONCLUSION: Reflecting muscle weakness and wasting, Pompe disease is associated with markedly reduced maximal exercise capacity. However, glycogenolysis is not impaired in exercise. Unlike in other metabolic myopathies, skeletal muscle substrate use during exercise is normal in Pompe disease rendering exercise less complicated for e.g. medical or recreational purposes.
OBJECTIVE: Pompe disease (glycogenosis type II) is caused by lysosomal alpha-glucosidase deficiency, which leads to a block in intra-lysosomal glycogen breakdown. In spite of enzyme replacement therapy, Pompe disease continues to be a progressive metabolic myopathy. Considering the health benefits of exercise, it is important in Pompe disease to acquire more information about muscle substrate use during exercise. METHODS: Seven adults with Pompe disease were matched to a healthy control group (1:1). We determined (1) peak oxidative capacity (VO2peak) and (2) carbohydrate and fatty acid metabolism during submaximal exercise (33 W) for 1 h, using cycle-ergometer exercise, indirect calorimetry and stable isotopes. RESULTS: In the patients, VO2peak was less than half of average control values; mean difference -1659 mL/min (CI: -2450 to -867, P = 0.001). However, the respiratory exchange ratio increased to >1.0 and lactate levels rose 5-fold in the patients, indicating significant glycolytic flux. In line with this, during submaximal exercise, the rates of oxidation (ROX) of carbohydrates and palmitate were similar between patients and controls (mean difference 0.226 g/min (CI: 0.611 to -0.078, P = 0.318) and mean difference 0.016 µmol/kg/min (CI: 1.287 to -1.255, P = 0.710), respectively). CONCLUSION: Reflecting muscle weakness and wasting, Pompe disease is associated with markedly reduced maximal exercise capacity. However, glycogenolysis is not impaired in exercise. Unlike in other metabolic myopathies, skeletal muscle substrate use during exercise is normal in Pompe disease rendering exercise less complicated for e.g. medical or recreational purposes.
Authors: Harrison N Jones; Maragatha Kuchibhatla; Kelly D Crisp; Lisa D Hobson-Webb; Laura Case; Milisa T Batten; Jill A Marcus; Richard M Kravitz; Priya S Kishnani Journal: Neuromuscul Disord Date: 2020-09-28 Impact factor: 4.296
Authors: Harrison N Jones; Maragatha Kuchibhatla; Kelly D Crisp; Lisa D Hobson Webb; Laura Case; Milisa T Batten; Jill A Marcus; Richard M Kravitz; Priya S Kishnani Journal: Mol Genet Metab Date: 2019-05-08 Impact factor: 4.797
Authors: Gerben J Schaaf; Tom J M van Gestel; Stijn L M In 't Groen; Bart de Jong; Björn Boomaars; Antonietta Tarallo; Monica Cardone; Giancarlo Parenti; Ans T van der Ploeg; W W M Pim Pijnappel Journal: Acta Neuropathol Commun Date: 2018-11-07 Impact factor: 7.801