TY - JOUR

T1 - Hydroxylated Long-Chain Acylcarnitines are Biomarkers of Mitochondrial Myopathy

AU - Vissing, Christoffer Rasmus

AU - Dunø, Morten

AU - Wibrand, Flemming

AU - Christensen, Mette

AU - Vissing, John

N1 - Copyright © 2019 Endocrine Society.

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

U2 - 10.1210/jc.2019-00721

DO - 10.1210/jc.2019-00721

M3 - Journal article

C2 - 31294795

VL - 104

SP - 5968

EP - 5976

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 12

ER -