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 [La]p 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 < 0.05) lower peak values of V̇O₂, 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.