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

## TL;DR

People with glycogen storage disease type III have reduced exercise tolerance due to issues with oxygen transport and muscle efficiency.

## Contribution

This study identifies specific cardiopulmonary and skeletal muscle strategies in GSDIII-p during exercise.

## Key findings

- GSDIII-p showed significantly lower peak VO2, ventilation, lactate, and oxygen extraction compared to controls.
- Exercise intolerance in GSDIII-p is linked to increased respiratory frequency and inadequate tidal volume adaptation.
- Reduced exercise tolerance is attributed to respiratory and skeletal muscle inefficiencies in GSDIII-p.

## Abstract

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.