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

E. F. Diekman, G. Visser, J. P. J. Schmitz, R. A. J. Nievelstein, M. de Sain-van der Velden, M. Wardrop, W. L. Van der Pol, S. M. Houten, N. A. W. van Riel, T. Takken, J. A. L. Jeneson*

*Bijbehorende auteur voor dit werk

    OnderzoeksoutputAcademicpeer review

    33 Citaten (Scopus)
    275 Downloads (Pure)


    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 not because of failing mitochondrial function. Our findings provide new clues to understanding the risk of rhabdomyolysis following exercise in human VLCADD.

    Originele taal-2English
    Aantal pagina's19
    TijdschriftPLoS ONE
    Nummer van het tijdschrift2
    StatusPublished - 16-feb.-2016

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