Department of Neurology, Copenhagen Neuromuscular Center, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Department of Clinical Genetics, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
J Clin Endocrinol Metab. 2019 Dec 1;104(12):5968-5976. doi: 10.1210/jc.2019-00721.
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.
We hypothesized that acylcarnitines can also be biomarkers of mitochondrial myopathy and sought to investigate the prevalence and pattern of elevated acylcarnitines.
This was a prospective cohort study of patients with confirmed mitochondrial myopathy followed at Copenhagen Neuromuscular Center, Rigshospitalet, Copenhagen, Denmark.
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.
Prevalence of elevated concentrations of acylcarnitines related to acyl-coenzyme A (CoA) dehydrogenases in patients with mitochondrial myopathy and relation to genotypes/phenotypes.
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.
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.
血浆酰基肉碱是β-氧化的生物标志物，可用于诊断多种先天性代谢错误，但从未在患有线粒体肌病的患者中进行过系统研究。
我们假设酰基肉碱也可以作为线粒体肌病的生物标志物，并试图研究升高的酰基肉碱的患病率和模式。
这是一项在丹麦哥本哈根神经肌肉中心 Rigshospitalet 对确诊的线粒体肌病患者进行的前瞻性队列研究。
我们纳入了 35 名线粒体肌病患者（44±15 岁，15 名女性），这些患者的线粒体肌病是由线粒体 DNA 大片段缺失（n=17）、线粒体转移 RNA 的致病性变异（n=13）或呼吸链复合物的蛋白质引起的（n=5）。使用超高效液相色谱和串联质谱法测量 35 种酰基肉碱的浓度。将这些发现与所有患者的肌肉突变负荷进行比较，并与 26 名患者的呼吸链活性进行比较。
与酰基辅酶 A（CoA）脱氢酶相关的酰基肉碱浓度升高在患有线粒体肌病的患者中的患病率，以及与基因型/表型的关系。
总共 27 名（77%）患者的酰基肉碱浓度升高与酰基辅酶 A 脱氢酶有关。与 >900 名个体的对照组相比，22 名（63%）患者中七种酰基肉碱的浓度升高更为常见，22 名（63%）患者中出现了涉及羟化长链酰基肉碱的特定模式。紊乱的严重程度与肌肉突变负荷和基因型/表型相关。
总之，升高的酰基肉碱浓度在患有线粒体肌病的患者中很常见，并且表现出影响羟化长链酰基肉碱的特定模式，这可能对未来患者的诊断工作有影响。
