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Randomized Controlled Trial
. 2025 Sep 24;20(1):485.
doi: 10.1186/s13023-025-04013-7.

Exercise capacity in RYR1-related myopathies

Lisa M K Chin  1 , Joshua J Todd  2   3 , Irene C Chrismer  4   5 , Jessica W Witherspoon  5 , Minal Jain  1 , Melissa Waite  1 , Katherine G Meilleur  5 , Bart Drinkard  1 , Tokunbor A Lawal  6   7   8
Affiliations
Randomized Controlled Trial

Exercise capacity in RYR1-related myopathies

Lisa M K Chin et al. Orphanet J Rare Dis. .

Abstract

Background: Pathogenic variations affecting the ryanodine receptor 1 (RYR1) gene may result in a variety of neuromuscular disorders, collectively known as RYR1-related myopathies. Considered the most common form of congenital myopathy, individuals with RYR1-related myopathies may experience skeletal muscle weakness and fatigue, as well as reduced functional capacity. This study examined the exercise capacity in individuals with RYR1-related myopathies during a cardiopulmonary exercise test.

Methods: Ambulatory individuals (32 adults, 16 children) with genetically confirmed RYR1-related myopathies performed exercise testing on a cycle ergometer and a six-minute walk test at baseline and month six (pre-intervention phase) of a randomized controlled trial (NCT02362425). Outcomes at peak exercise were compared to expected values among the adult and pediatric populations, while longitudinal changes were assessed after six months. Correlations between peak exercise outcomes and the six-minute walk test distance were also examined.

Results: The peak outcomes of oxygen uptake, work rate and heart rate at baseline were lower (all p < 0.001) than expected in both adults and children. Peak oxygen uptake expressed as percent predicted was 62 ± 20% and 49 ± 24% in adults and children, respectively. No changes were observed across six months for peak exercise outcomes in either group. A moderately strong positive correlation was observed for peak work rate and six-minute walk test distance among adults (rs = 0.75, p < 0.001) and children (rs = 0.64, p = 0.008).

Conclusion: Exercise capacity is diminished in adults and children with RYR1-related myopathies yet remains stable over six months. The six-minute walk test distance had a direct relationship to peak exercise work rate in adults and children. Exercise capacity testing may be informative for individualizing exercise regimens for persons with RYR1-related myopathies. This study was registered with www.

Clinicaltrials: gov (NCT02362425) on February 12, 2015.

Keywords: Exercise test; Muscular diseases; Oxygen consumption; Walk test.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study was approved by the National Institutes of Health (NIH) Combined Neuroscience Institutional Review Board (IRB) and performed in accordance with the Declaration of Helsinki. Informed consent was obtained from all individual participants included in the study. Consent for publication: Not applicable. Competing Interests: Financial interests: JJT, JWW, KGM and TAL received research support from the RYR-1 Foundation. All other authors (LMKC, ICC, MJ, MW, BD) declare they have no financial interests relevant to this manuscript. Non-financial interests: MJ serves on the scientific advisory board for the RYR-1 Foundation.

Figures

Fig. 1
Fig. 1
Percent predicted for select peak CPET variables for RYR1-RM adults. Standard box plot with ranges (Q1 to Q3), median (line), mean (square symbol), 1.5 times interquartile range (whiskers) and outliers (diagonal cross symbol), and individual participants (circle symbols) shown. Symbols in black denote adults with recessive mode of inheritance. Dashed line denotes expected response (i.e., 100% predicted). Grey areas denote abnormal cut-offs from [20]
Fig. 2
Fig. 2
Spearman’s correlation with 95% CI [lower to upper] bounds between indices at peak exercise and 6MWT distance at baseline (month-0) for adults (circle symbols; left panels) and children (square symbols; right panels). Symbols in black denote participants with recessive mode of inheritance
Fig. 3
Fig. 3
The Metabolic Equivalent of Task (MET) at the ventilatory anaerobic threshold (AT) and peak exercise for adults with RYR1-RM. Standard box plot with ranges (Q1 to Q3), median (line), mean (square symbol), 1.5 times interquartile range (whiskers) and outliers (diagonal cross symbols) shown, with individual data points (circle symbols). Dashed lines demarcate level of absolute intensity in MET for light (< 3 MET), moderate (≥ 3 and < 6 MET), and vigorous (≥ 6 MET) per [48]. Symbols in black denote adult participants with recessive mode of inheritance
See this image and copyright information in PMC

References

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