Cardiopulmonary and skeletal muscle strategies underlying exhaustive exercise in adults with glycogen storage disease type III

People with glycogen storage disease type III (GSDIII-p) have a remarkably reduced exercise tolerance. Aim of this study was to analyze the oxygen transport-utilization chain strategies adopted by GSDIII-p during exercise. Nine GSDIII-p (39.4 ± 10.0 year, 33% female) and 11 healthy controls (CTRL), age and gender matched, underwent an incremental cardiopulmonary exhaustion test (CPET) to assess peak heart rate (HR), blood lactate Lap and vastus lateralis O2 fractional extraction (ΔHHb/isch) using near-infrared spectroscopy. Patterns of breathing (PBr) were assessed accordingly by analyzing pulmonary O2 uptake (V̇O2), tidal volume (Vt), respiratory frequency (Rf), end-tidal CO2 (PETCO2) and alveolar ventilation (V̇A). GSDIII-p exhibited significantly (p 2, pulmonary ventilation (V̇E) La and ΔHHb/isch compared to CTRL (1.7 ± 0.7 vs. 3.2 ± 1.1 L/min, 50.5 ± 19.8 vs. 113.6 ± 40.4 L/min, 1.8 ± 0.7 vs. 7.6 ± 3.0 mmol/L and 39.1% ± 9.9% vs. 74.8% ± 36.6%, respectively). The range of peak V̇O2 values for GSDIII-p, compared to the predicted values for age and sex, was between 79% and 35%. Both GSDIII-p and CTRL were arbitrarily divided into 4 groups according to individual V̇E values. GSDIII-p with exercise intolerance relied on increased Rf with inadequate Vt adaptation to maintain V̇E and reduce PETCO2, with low V̇A values and low to moderate workloads tolerance. Reduced exercise tolerance in GSDIII-p is related to respiratory and skeletal muscle inefficiencies. GSDIII-p strong heterogeneity evaluated throught CPET provides insights into clinical management.