Altered Energetics of Exercise Explain Risk of Rhabdomyolysis in Very Long-Chain Acyl-CoA Dehydrogenase Deficiency

PloS One
E F DiekmanJeroen A L Jeneson

Abstract

Rhabdomyolysis is common in very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) and other metabolic myopathies, but its pathogenic basis is poorly understood. Here, we show that prolonged bicycling exercise against a standardized moderate workload in VLCADD patients is associated with threefold bigger changes in phosphocreatine (PCr) and inorganic phosphate (Pi) concentrations in quadriceps muscle and twofold lower changes in plasma acetyl-carnitine levels than in healthy subjects. This result is consistent with the hypothesis that muscle ATP homeostasis during exercise is compromised in VLCADD. However, the measured rates of PCr and Pi recovery post-exercise showed that the mitochondrial capacity for ATP synthesis in VLCADD muscle was normal. Mathematical modeling of oxidative ATP metabolism in muscle composed of three different fiber types indicated that the observed altered energy balance during submaximal exercise in VLCADD patients may be explained by a slow-to-fast shift in quadriceps fiber-type composition corresponding to 30% of the slow-twitch fiber-type pool in healthy quadriceps muscle. This study demonstrates for the first time that quadriceps energy balance during exercise in VLCADD patients is altered but n...Continue Reading

Associated Clinical Trials

Jan 5, 2017·Terry G.J. Derks, MD, PhD
May 21, 2018·dr. J.A.L. Jeneson

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Citations

Sep 6, 2017·Journal of Inherited Metabolic Disease·Melanie B GillinghamJerry Vockley
Jan 20, 2020·Journal of Inherited Metabolic Disease·Jeannette C BleekerJeroen A L Jeneson
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Jun 14, 2019·Frontiers in Physiology·Alba M Herrera-OlivaresAlfredo Santalla
May 29, 2020·Journal of Inherited Metabolic Disease·Suzan J G KnottnerusAdrianus J Bakermans
Jul 13, 2020·Reviews in Endocrine & Metabolic Disorders·J Lawrence MerrittBryan Hainline
Jan 30, 2019·Pediatric Exercise Science·Marco Van BrusselTim Takken
Feb 18, 2020·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Suzan J G KnottnerusMonique G M de Sain-van der Velden
Sep 16, 2020·Molecular Genetics and Metabolism·Gabriela ElizondoMelanie B Gillingham
May 1, 2021·International Journal of Molecular Sciences·Sara TucciZeinab Wehbe
Jul 2, 2021·Clinical & Translational Immunology·Abbe N VallejoJerry Vockley

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Methods Mentioned

BETA
nuclear magnetic resonance
dissection
biopsy
transgenic

Software Mentioned

FATMAX
jMRUI
AMARES
Origin
VLCADD
Matlab

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