Context: Plasma acylcarnitines are biomarkers of β-oxidation and are useful in diagnosing several inborn errors of metabolism but have never been investigated systematically in patients with mitochondrial myopathy.
Objective: We hypothesized that acylcarnitines can also be biomarkers of mitochondrial myopathy and sought to investigate the prevalence and pattern of elevated acylcarnitines.
Design: This was a prospective cohort study of patients with confirmed mitochondrial myopathy followed at Copenhagen Neuromuscular Center, Rigshospitalet, Copenhagen, Denmark.
Patients: We included 35 patients (44 ± 15 years, 15 women) with mitochondrial myopathy caused by single, large-scale deletions of mitochondrial DNA (n = 17), pathogenic variants in mitochondrial transfer RNA (n = 13), or in proteins of the respiratory chain complexes (n = 5).Concentrations of 35 acylcarnitines were measured using ultra-HPLC and tandem mass-spectrometry. Findings were compared with muscle mutation load in all patients and to respiratory chain activity in 26 patients.
Main outcome measures: Prevalence of elevated concentrations of acylcarnitines related to acyl-coenzyme A (CoA) dehydrogenases in patients with mitochondrial myopathy and relation to genotypes/phenotypes.
Results: In total, 27 (77%) patients had elevated concentrations of acylcarnitines related to acyl-CoA dehydrogenases. Elevated concentrations of seven acylcarnitine species were more common in patients compared with a control cohort of >900 individuals, and a specific pattern involving hydroxylated long-chain acylcarnitines occurred in 22 (63%) patients. Severity of derangements was correlated with muscle mutation load and genotypes/phenotypes.
Conclusion: In conclusion, elevated concentrations of acylcarnitines is common in patients with mitochondrial myopathy and shows a specific pattern affecting hydroxylated long-chain acylcarnitines, which can have implications for future diagnostic workup of patients.
Copyright © 2019 Endocrine Society.