原发性线粒体肌病：来自意大利的118例患者的临床特征及疗效评估
Primary mitochondrial myopathy: Clinical features and outcome measures in 118 cases from Italy.
作者信息
Montano Vincenzo, Gruosso Francesco, Carelli Valerio, Comi Giacomo Pietro, Filosto Massimiliano, Lamperti Costanza, Mongini Tiziana, Musumeci Olimpia, Servidei Serenella, Tonin Paola, Toscano Antonio, Modenese Angela, Primiano Guido, Valentino Maria Lucia, Bortolani Sara, Marchet Silvia, Meneri Megi, Tavilla Graziana, Siciliano Gabriele, Mancuso Michelangelo
机构信息
Department of Clinical and Experimental Medicine (V.M., F.G., G.S., M.M.), Neurological Clinic, University of Pisa, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (V.C., M.L.V.), UOC Clinica Neurologica, Bologna, Italy; Department of Biomedical and Neuromotor Sciences (DIBINEM) (V.C., M.L.V.), University of Bologna, Italy; Dino Ferrari Centre (G.P.C.), Department of Pathophysiology and Transplantation (DEPT), University of Milan, Italy; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (G.P.C., M.M.), Neuromuscular and Rare Disease Unit; Unit of Neurology (M.F.), ASST "Spedali Civili" and University of Brescia, Italy; UO Medical Genetics and Neurogenetics (C.L., S.M.), Fondazione IRCCS Istituto Neurologico C.Besta, Milan, Italy; Neuromuscular Unit (M.T., S.B.), Department of Neurosciences, University of Torino, Italy; Department of Clinical and Experimental Medicine (O.M., A.T., G.T.), UOC Neurologia e Malattie Neuromuscolari, University of Messina, Italy; UOC Neurofisiopatologia Fondazione Policlinico Universitario A. Gemelli IRCCS (S.S., G.P.), Roma, Italy; Dipartimento Universitario di Neuroscienze, Università Cattolica del Sacro Cuore (S.S., G.P.), Roma, Italy; Department of Neurosciences (P.T.), Biomedicine and Movement Sciences, Section of Clinical Neurology, University of Verona, Italy; Neurorehabilitation Unit (A.M.), Department of Neurosciences, University Hospital of Verona, Italy; Neuromuscular Unit (S.B.), Department of Neurosciences, University of Torino, Italy.
出版信息
Neurol Genet. 2020 Oct 20;6(6):e519. doi: 10.1212/NXG.0000000000000519. eCollection 2020 Dec.
OBJECTIVE
To determine whether a set of functional tests, clinical scales, patient-reported questionnaires, and specific biomarkers can be considered reliable outcome measures in patients with primary mitochondrial myopathy (PMM), we analyzed a cohort of Italian patients.
METHODS
Baseline data were collected from 118 patients with PMM, followed by centers of the Italian network for mitochondrial diseases. We used the 6-Minute Walk Test (6MWT), Timed Up-and-Go Test (x3) (3TUG), Five-Times Sit-To-Stand Test (5XSST), Timed Water Swallow Test (TWST), and Test of Masticating and Swallowing Solids (TOMASS) as functional outcome measures; the Fatigue Severity Scale and West Haven-Yale Multidimensional Pain Inventory as patient-reported outcome measures; and FGF21, GDF15, lactate, and creatine kinase (CK) as biomarkers.
RESULTS
A total of 118 PMM cases were included. Functional outcome measures (6MWT, 3TUG, 5XSST, TWST, and TOMASS) and biomarkers significantly differed from healthy reference values and controls. Moreover, functional measures correlated with patients' perceived fatigue and pain severity. Patients with either mitochondrial or nuclear DNA point mutations performed worse in functional measures than patients harboring single deletion, even if the latter had an earlier age at onset but similar disease duration. Both the biomarkers FGF21 and GDF15 were significantly higher in the patients compared with a matched control population; however, there was no relation with severity of disease.
CONCLUSIONS
We characterized a large cohort of PMM by evaluating baseline mitochondrial biomarkers and functional scales that represent potential outcome measures to monitor the efficacy of treatment in clinical trials; these outcome measures will be further reinvestigated longitudinally to define the natural history of PMM.
目的
为了确定一组功能测试、临床量表、患者报告问卷和特定生物标志物是否可被视为原发性线粒体肌病（PMM）患者可靠的结局指标，我们分析了一组意大利患者。
方法
从118例PMM患者收集基线数据，这些患者由意大利线粒体疾病网络中心随访。我们使用6分钟步行试验（6MWT）、计时起立行走试验（x3）（3TUG）、五次坐立试验（5XSST）、定时饮水吞咽试验（TWST）和咀嚼与吞咽固体试验（TOMASS）作为功能结局指标；使用疲劳严重程度量表和西黑文-耶鲁多维疼痛量表作为患者报告结局指标；使用成纤维细胞生长因子21（FGF21）、生长分化因子15（GDF15）、乳酸和肌酸激酶（CK）作为生物标志物。
结果
共纳入118例PMM病例。功能结局指标（6MWT、3TUG、5XSST、TWST和TOMASS）和生物标志物与健康参考值及对照组相比有显著差异。此外，功能指标与患者感知的疲劳和疼痛严重程度相关。线粒体或核DNA点突变的患者在功能指标上比单一缺失的患者表现更差，即使后者发病年龄更早但病程相似。与匹配的对照人群相比，患者体内的生物标志物FGF21和GDF15均显著升高；然而，与疾病严重程度无关。
结论
我们通过评估基线线粒体生物标志物和功能量表对一大群PMM患者进行了特征分析，这些指标代表了在临床试验中监测治疗效果的潜在结局指标；这些结局指标将进一步进行纵向重新研究以明确PMM的自然病史。
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