Hydroxylated long-chain acylcarnitines are biomarkers of mitochondrial myopathy

Abstract

Abstract Context Plasma acylcarnitines are biomarkers of beta-oxidation and are useful in diagnosing several inborn errors of metabolism but has never been systematically investigated 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 The study 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 mt-DNA (n=17), pathogenic variants in mt-tRNA (n=13) or in proteins of the respiratory chain complexes (n=5). Concentrations of 35 acylcarnitines were measured using ultra-high-performance liquid-chromatography and tandem mass-spectrometry. Findings were compared to 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-CoA dehydrogenases in patients with mitochondrial myopathy and relation to geno-/phenotypes. Results In total, 27 (77%) patients had elevated concentrations of acylcarnitines related to acyl-CoA dehydrogenases. Elevated concentrations of seven acylcarnitine species were significantly more common in patients compared to 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 geno-/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 work-up of patients.