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.

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.

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.

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.

为了确定一组功能测试、临床量表、患者报告的问卷和特定的生物标志物是否可以被认为是原发性线粒体肌病 (PMM) 患者的可靠结果测量，我们分析了一组意大利患者。

基线数据来自 118 名 PMM 患者，其次是意大利线粒体疾病网络中心。我们使用了 6 分钟步行测试 (6MWT)、定时起跳测试 (x3) (3TUG)、五次坐站测试 (5XSST)、定时吞水测试 (TWST) 和咀嚼和吞咽固体（TOMASS）作为功能结果测量；疲劳严重程度量表和 West Haven-Yale 多维疼痛量表作为患者报告的结果测量；和 FGF21、GDF15、乳酸和肌酸激酶 (CK) 作为生物标志物。

共纳入 118 例 PMM 病例。功能结果测量（6MWT、3TUG、5XSST、TWST 和 TOMASS）和生物标志物与健康参考值和对照显着不同。此外，功能测量与患者感知到的疲劳和疼痛严重程度相关。具有线粒体或核 DNA 点突变的患者在功能测量中的表现比具有单一缺失的患者更差，即使后者的发病年龄较早但疾病持续时间相似。与匹配的对照人群相比，患者的生物标志物 FGF21 和 GDF15 均显着升高；然而，与疾病的严重程度无关。

我们通过评估基线线粒体生物标志物和功能量表来表征一大群 PMM，这些标志物和功能量表代表了在临床试验中监测治疗效果的潜在结果指标；这些结果措施将进一步纵向重新调查，以确定 PMM 的自然史。