McArdle disease (Glycogen Storage Disease Type V) from an exercise physiology and biochemistry perspective: Important considerations for exercise and physical activity testing and data interpretation

Traditionally, the management and research of inborn errors of metabolism have been primarily overseen by genetic specialists, whose expertise has guided both therapeutic strategies and efforts to identify potential cures. In more recent times, exercise scientists and exercise physiologists have been shown to provide important insights into these conditions from new perspectives. Because exercise and physical activity testing is often used to determine the main outcome variables for interventions designed to improve the lives of those with inborn errors of metabolism, it is logical that exercise specialists are involved in research design and data interpretation.

This article aims to provide important exercise and physical activity testing guidance and advice for researchers of McArdle disease (MD) with evidence-based rationale to help improve data interpretation and the validity of research outcomes for future research. The article presents clear definitions and examples of concepts commonly used in exercise and physical activity research (i.e., absolute and relative intensity) and outlines methodological considerations that may compromise results interpretation (i.e., the use of broad exercise intensity ranges, pretesting liver glycogen standardisation). Additionally, the article discusses important considerations and limitations in using exercise testing metrics in MD populations, and their associated interpretations, that have been previously validated in non-MD populations (i.e., maximal rate of oxygen consumption $\left[\dot{\mathrm{V}}{\mathrm{O}}_{2\mathrm{m}\mathrm{a}\mathrm{x}}\right]$, peak rate of oxygen consumption $\left[\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}\right]$, and respiratory exchange ratios [RER]). The information presented will act as an important reference point for future research design and data interpretation for exercise and physical activity testing with MD cohorts.

Inevitably, prior research forms the foundations to future advances which places an important responsibility on all scientists to design robust research methodologies, produce valid and reliable results, identify limitations to their outcomes, and to interpret and apply these results correctly.