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

Adults with glycogen storage disease type III (GSDIII-p) exhibited significantly lower peak oxygen uptake compared to healthy controls.

• Peak VO2 was 1.7 ± 0.7 L/min in GSDIII-p versus 3.2 ± 1.1 L/min in CTRL (p < 0.05)
• The range of peak VO2 values for GSDIII-p, compared to the predicted values for age and sex, was between 79% and 35%
• Nine GSDIII-p (39.4 ± 10.0 years, 33% female) and 11 healthy age- and gender-matched controls underwent incremental cardiopulmonary exhaustion testing (CPET)

GSDIII-p showed significantly lower peak pulmonary ventilation compared to healthy controls.

• Peak pulmonary ventilation (VE) was 50.5 ± 19.8 L/min in GSDIII-p versus 113.6 ± 40.4 L/min in CTRL (p < 0.05)
• GSDIII-p with exercise intolerance relied on increased respiratory frequency (Rf) with inadequate tidal volume (Vt) adaptation to maintain VE
• Low alveolar ventilation (VA) values were observed in GSDIII-p with exercise intolerance

GSDIII-p demonstrated significantly lower peak blood lactate concentrations during exhaustive exercise compared to controls.

• Peak blood lactate [La]p was 1.8 ± 0.7 mmol/L in GSDIII-p versus 7.6 ± 3.0 mmol/L in CTRL (p < 0.05)
• The markedly blunted lactate response is consistent with impaired glycogenolysis characteristic of GSDIII

GSDIII-p exhibited significantly lower vastus lateralis oxygen fractional extraction during exercise compared to healthy controls.

• Peak O2 fractional extraction (ΔHHb/isch) was 39.1% ± 9.9% in GSDIII-p versus 74.8% ± 36.6% in CTRL (p < 0.05)
• Skeletal muscle O2 extraction was assessed using near-infrared spectroscopy (NIRS) at the vastus lateralis
• Reduced O2 extraction reflects skeletal muscle inefficiency as a contributor to exercise intolerance in GSDIII-p

GSDIII-p with exercise intolerance demonstrated an inefficient breathing pattern characterized by increased respiratory frequency with inadequate tidal volume adaptation.

• Subjects were arbitrarily divided into 4 groups according to individual VE values to analyze breathing pattern strategies
• GSDIII-p with lower exercise tolerance showed increased Rf with inadequate Vt adaptation to maintain VE and reduce PETCO2
• Low alveolar ventilation (VA) values were associated with low to moderate workload tolerance in GSDIII-p
• Patterns of breathing were assessed by analyzing pulmonary O2 uptake (VO2), tidal volume (Vt), respiratory frequency (Rf), end-tidal CO2 (PETCO2), and alveolar ventilation (VA)

GSDIII-p demonstrated strong heterogeneity in exercise capacity as evaluated through CPET.

• Peak VO2 values as a percentage of predicted ranged widely from 35% to 79% across individual GSDIII-p patients
• This heterogeneity was observed across cardiopulmonary, ventilatory, and skeletal muscle parameters
• The authors note that GSDIII-p strong heterogeneity evaluated through CPET provides insights into clinical management