Physical exercise intervention in glycogen storage disease IIIa: Feasibility and multisystem benefits

Glycogen storage disease III (GSD-III) is caused by an inherited deficiency of the glycogen debranching enzyme. Affecting the liver, muscle and heart, GSD-IIIa is the most common GSD-III subtype. We evaluated the feasibility and safety of a physical exercise intervention in patients with GSD-IIIa and its effects at the multisystem level. Nine patients (four female; five children and four adults; 60% of all diagnosed Spanish patients) participated in a 12 week home-based, remotely supervised programme combining moderate-intensity endurance and resistance exercises. Training tolerance/adaptation (fatigue severity scale, wellbeing questionnaire) and safety were assessed throughout the intervention period. The following outcomes were determined at baseline and postintervention: Health-related quality of life; muscle, liver, kidney and cardiac damage/function biomarkers; dual X-ray absorptiometry-determined fat/muscle/bone mass; echocardiography-determined cardiac dimensions and left ventricular global longitudinal strain; endurance capacity indicators during cardiopulmonary exercise testing; and muscle strength. The patients completed a median of 88% (interquartile range, 87%-100%) of the prescribed sessions. The intervention was safe and well tolerated, with no changes in wellbeing over time and with a decrease in perceived fatigue severity during the intervention (p = 0.002). Barring alanine aminotransferase, there were no changes in blood biomarkers, and the following significant effects were found at postintervention: Decrease in visceral adipose tissue (p = 0.038); healthier cardiac geometry [from concentric to normal remodelling, with decreases in relative (p = 0.015) and posterior (p = 0.042) wall thickness]; and increases in peak oxygen uptake (p = 0.033), peak power output (p = 0.017) and knee-extension isometric strength (p = 0.012). Although more research is needed, the present findings suggest that exercise should be considered in GSD-IIIa management.