Skeletal muscle metabolism is impaired during exercise in glycogen storage disease type III

TY - JOUR

T1 - Skeletal muscle metabolism is impaired during exercise in glycogen storage disease type III

AU - Preisler, Nicolai

AU - Laforêt, Pascal

AU - Madsen, Karen Lindhardt

AU - Prahm, Kira Philipsen

AU - Hedermann, Gitte

AU - Vissing, Christoffer Rasmus

AU - Galbo, Henrik

AU - Vissing, John

N1 - © 2015 American Academy of Neurology.

PY - 2015/4/28

Y1 - 2015/4/28

N2 - OBJECTIVE: Glycogen storage disease type IIIa (GSDIIIa) is classically regarded as a glycogenosis with fixed weakness, but we hypothesized that exercise intolerance in GSDIIIa is related to muscle energy failure and that oral fructose ingestion could improve exercise tolerance in this metabolic myopathy.METHODS: We challenged metabolism with cycle-ergometer exercise and measured substrate turnover and oxidation rates using stable isotope methodology and indirect calorimetry in 3 patients and 6 age-matched controls on 1 day, and examined the effect of fructose ingestion on exercise tolerance in the patients on another day.RESULTS: Total fatty acid oxidation rates during exercise were higher in patients than controls, 32.1 (SE 1.2) vs 20.7 (SE 0.5; range 15.8-29.3) μmol/kg/min (p = 0.048), and oxidation of carbohydrates was lower in patients, 1.0 (SE 5.4) vs 38.4 (SE 8.0; range 23.0-77.1) μmol/kg/min (p = 0.024). Fructose ingestion improved exercise tolerance in the patients.CONCLUSION: Similar to patients with McArdle disease, in whom muscle glycogenolysis is also impaired, GSDIIIa is associated with a reduced skeletal muscle oxidation of carbohydrates and a compensatory increase in fatty acid oxidation, and fructose ingestion improves exercise tolerance. Our results indicate that GSDIIIa should not only be viewed as a glycogenosis with fixed skeletal muscle weakness, but should also be considered among the glycogenoses presenting with exercise-related dynamic symptoms caused by muscular energy deficiency.CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that ingestion of fructose improves exercise tolerance in patients with GSDIIIa.

AB - OBJECTIVE: Glycogen storage disease type IIIa (GSDIIIa) is classically regarded as a glycogenosis with fixed weakness, but we hypothesized that exercise intolerance in GSDIIIa is related to muscle energy failure and that oral fructose ingestion could improve exercise tolerance in this metabolic myopathy.METHODS: We challenged metabolism with cycle-ergometer exercise and measured substrate turnover and oxidation rates using stable isotope methodology and indirect calorimetry in 3 patients and 6 age-matched controls on 1 day, and examined the effect of fructose ingestion on exercise tolerance in the patients on another day.RESULTS: Total fatty acid oxidation rates during exercise were higher in patients than controls, 32.1 (SE 1.2) vs 20.7 (SE 0.5; range 15.8-29.3) μmol/kg/min (p = 0.048), and oxidation of carbohydrates was lower in patients, 1.0 (SE 5.4) vs 38.4 (SE 8.0; range 23.0-77.1) μmol/kg/min (p = 0.024). Fructose ingestion improved exercise tolerance in the patients.CONCLUSION: Similar to patients with McArdle disease, in whom muscle glycogenolysis is also impaired, GSDIIIa is associated with a reduced skeletal muscle oxidation of carbohydrates and a compensatory increase in fatty acid oxidation, and fructose ingestion improves exercise tolerance. Our results indicate that GSDIIIa should not only be viewed as a glycogenosis with fixed skeletal muscle weakness, but should also be considered among the glycogenoses presenting with exercise-related dynamic symptoms caused by muscular energy deficiency.CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that ingestion of fructose improves exercise tolerance in patients with GSDIIIa.

KW - Adolescent

KW - Adult

KW - Energy Metabolism

KW - Exercise

KW - Fructose

KW - Glycogen Storage Disease Type III

KW - Humans

KW - Muscle Weakness

KW - Muscle, Skeletal

KW - Young Adult

U2 - 10.1212/WNL.0000000000001518

DO - 10.1212/WNL.0000000000001518

M3 - Journal article

C2 - 25832663

SN - 0028-3878

VL - 84

SP - 1767

EP - 1771

JO - Neurology

JF - Neurology

IS - 17

ER -