Appendicular skeletal muscle mass: A more sensitive biomarker of disease severity than BMI in adults with mitochondrial diseases

The study aimed to evaluate the body composition of patients with mitochondrial diseases (MD) and correlate it with disease severity. Overall, 89 patients (age ≥ 18 years) with MD were recruited, including 49 with chronic progressive external ophthalmoplegia (CPEO) and 40 with mitochondrial encephalomyopathy with lactate acidosis and stroke-like episodes (MELAS). Body composition, including fat mass index (FMI), fat-free mass index (FFMI), skeletal muscle mass index (SMI), and appendicular skeletal muscle mass index (ASMI), were examined using multifrequency bioelectric impedance analysis. Clinical assessments, including muscle strength, usual gait speed, and disease severity determined by the Newcastle Mitochondrial Disease Adult Scale score (NMDAS), were performed. The comparisons between patients group and age- and gender-matched healthy controls, as well as the correlations between anthropometric measurements, body composition, and disease severity were analyzed. Height, weight, body mass index (BMI), FFMI, SMI, and ASMI were significantly lower in patients with MD than in healthy controls. Notably, low muscle mass was noted in 69.7% (62/89) of MD patients, with 22 patients also presenting with compromised physical performance as indicated by decreased gait speed, resulting in 24.7% satisfied the sarcopenia diagnostic criteria. Disease severity was more negatively correlated with ASMI than it was with height, weight, and BMI. Subgroup analysis showed that in the MELAS subgroup, disease severity was negatively correlated with height, weight, and ASMI; whereas in the CPEO subgroup, it was only negatively correlated with ASMI and SMI. Additionally, ASMI was positively associated with muscle strength. Altogether, compared with BMI, ASMI is a more sensitive biomarker predicting disease severity of MD, both in MELAS and CPEO patients.

本研究旨在评估线粒体疾病（mitochondrial diseases, MD）患者的身体组成，并分析其与疾病严重程度的相关性。研究共招募89例年龄≥18岁的MD患者，其中49例为慢性进行性眼外肌麻痹（chronic progressive external ophthalmoplegia, CPEO）患者，40例为线粒体脑肌病伴乳酸酸中毒和卒中样发作（mitochondrial encephalomyopathy with lactate acidosis and stroke-like episodes, MELAS）患者。采用多频生物电阻抗分析法检测受试者的身体组成指标，包括脂肪质量指数（fat mass index, FMI）、去脂体重指数（fat-free mass index, FFMI）、骨骼肌质量指数（skeletal muscle mass index, SMI）及四肢骨骼肌质量指数（appendicular skeletal muscle mass index, ASMI）。同时开展多项临床评估：包括肌力检测、日常步速评估，以及采用纽卡斯尔线粒体疾病成人量表评分（Newcastle Mitochondrial Disease Adult Scale score, NMDAS）评定疾病严重程度。本研究比较了患者组与年龄、性别匹配的健康对照组的各项指标，并分析了人体测量学指标、身体组成与疾病严重程度之间的相关性。结果显示，MD患者的身高、体重、体重指数（body mass index, BMI）、FFMI、SMI及ASMI均显著低于健康对照组。值得注意的是，69.7%（62/89）的MD患者存在肌肉量减少，其中22例患者同时出现步速降低提示的躯体功能受损，最终24.7%的患者符合肌少症诊断标准。疾病严重程度与ASMI的负相关性强于其与身高、体重及BMI的相关性。亚组分析结果表明，在MELAS亚组中，疾病严重程度与身高、体重及ASMI呈负相关；而在CPEO亚组中，疾病严重程度仅与ASMI及SMI呈负相关。此外，ASMI与肌力呈正相关。综上，相较于BMI，ASMI是预测MD患者（包括MELAS及CPEO患者）疾病严重程度的更敏感生物标志物。