Ivaniuk Alina, Anselm Irina A, Bowen Aaron, Cohen Bruce H, Eminoglu Fatma Tuba, Estrella Jane, Gallagher Renata C, Ganetzky Rebecca D, Gannon Jennifer, Gorman Grainne S, Greene Carol, Gropman Andrea L, Haas Richard H, Hirano Michio, Kapoor Seema, Karaa Amel, Koenig Mary Kay, Kornblum Cornelia, Kose Engin, Larson Austin, Lichter-Konecki Uta, Lopriore Piervito, Mancuso Michelangelo, McFarland Robert, Moe Aye Myat, Morava Eva, Ng Yi Shiau, Saneto Russell P, Scaglia Fernando, Sue Carolyn M, Tarnopolsky Mark, Walker Melissa A, Parikh Sumit, Cheuk-Wing Fung, Wong Tsz-Sum, Belaramani Kiran, Chan Chun-Kong, Chan Wing-Ki, Chan Wai-Lun Larry, Cheung Hon-Wing, Cheung Ka-Yin, Chang Shek-Kwan, Cheung Sing-Ngai, Cheung Tsz-Fung, Cheung Yuk-Fai, Chong Shuk-Ching Josephine, Chow Chi-Kwan Jasmine, Chung Hon-Yin B, Fan Sin-Ying Florence, Fok Wai-Ming Joshua, Fong Ka-Wing, Fung Tsui-Hang Sharon, Hui Kwok-Fai, Hui Ting-Hin, Hui Joannie, Ko Chun Hung, Kwan Min-Chung, Kwok Mei-Kwan Anne, Kwok Sung-Shing Jeffrey, Lai Moon-Sing, Lam Yau-On, Lam Ching-Wan, Lau Ming-Chung, Law Chun-Yiu Eric, Law Hiu-Fung, Lee Wing-Cheong, Hencher Lee Han-Chih, Leung Kin-Hang, Leung Kit-Yan, Li Siu-Hung, Ling Tsz-Ki Jacky, Liu Kam-Tim Timothy, Lo Fai-Man, Lui Colin, Luk Ching-On, Luk Ho-Ming, Ma Che-Kwan, Ma Karen, Ma Kam-Hung, Mew Yuen-Ni, Mo Alex, Hg Sui-Fun, Poon Wing-Kit Grace, Sheng Bun, Szeto Cheuk-Ling Charing, Tai Shuk-Mui, Tang Jing-Liang, Tse Choi-Ting Alan, Tsung Li-Yan Lilian, Wong Ho-Ming June, Wong Wing-Yin Winnie, Wong Kwok-Kui, Wong Suet-Na Sheila, Wong Chun-Nei Virginia, Wong Wai-Shan Sammy, Wong Chi-Kin Felix, Wu Shun-Ping, Wu Hiu-Fung Jerome, Yau Man-Mut, Yau Kin-Cheong Eric, Yeung Wai-Lan, Yeung Hon-Ming Jonas, Yip Kin-Keung Edwin, Wu Hui-Jun, Young Pui-Hong Terence, Yuan Gao, Yuen Yuet-Ping Liz, Yuen Chi-Lap
Epilepsy Center, Cleveland Clinic, OH.
Department of Neurology, Boston Children's Hospital, MA.
Neurology. 2025 Feb 25;104(4):e209779. doi: 10.1212/WNL.0000000000209779. Epub 2025 Jan 30.
Mitochondrial disorders are multiorgan disorders resulting in significant morbidity and mortality. We aimed to characterize death-associated factors in an international cohort of deceased individuals with mitochondrial disorders.
This cross-sectional multicenter observational study used data provided by 26 mitochondrial disease centers from 8 countries from January 2022 to March 2023. Individuals with genetically confirmed mitochondrial disorders were included, along with patients with clinically or genetically diagnosed Leigh syndrome. Collected data included demographic and genetic diagnosis variables, clinical phenotype, involvement of organs and systems, conditions leading to death, and supportive care. We defined pediatric and adult groups based on age at death before or after 18 years, respectively. We used Kruskal-Wallis with post hoc Dunn test with Bonferroni correction and Fisher exact test for comparisons, Spearman rank test for correlations, and multiple linear regression for multivariable analysis.
Data from 330 deceased individuals with mitochondrial disorders (191 [57.9%] pediatric) were analyzed. The shortest survival times were observed in hepatocerebral syndrome (median 0.3, interquartile range [IQR] 0.2-0.6 years) and mitochondrial cardiomyopathy (median 0.3, IQR 0.2-5.2 years) and the longest in chronic progressive external ophthalmoplegia plus (median 26.5, IQR 22.8-40.2 years) and sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (median 21.0, IQR 13.8-28.5 years). Respiratory failure and pulmonary infections were the most common conditions associated with death (52/330, 15.7% and 46/330, 13.9%, respectively). Noninvasive ventilation was required more often in children (57/191, 29.8%) than adults (12/139, 8.6%, < 0.001), as was nasogastric or gastric tube (131/191, 68.6% in children and 39/139, 28.1% in adults, < 0.001). On multivariate analysis, individuals with movement disorders and nuclear gene involvement had increased odds of any respiratory support use (OR 2.42 (95% CI 1.17-5.22) and OR 2.39 (95% CI 1.16-5.07), respectively).
This international collaboration highlights the importance of respiratory care and infection management and provides a reference for prognostication across different mitochondrial disorders.
线粒体疾病是多器官疾病，会导致较高的发病率和死亡率。我们旨在对一个国际队列中已故线粒体疾病患者的死亡相关因素进行特征分析。
这项横断面多中心观察性研究使用了2022年1月至2023年3月期间来自8个国家的26个线粒体疾病中心提供的数据。纳入了基因确诊的线粒体疾病患者，以及临床或基因诊断的 Leigh 综合征患者。收集的数据包括人口统计学和基因诊断变量、临床表型、器官和系统受累情况、导致死亡的病症以及支持性护理。我们分别根据死亡年龄在18岁之前或之后定义了儿童组和成人组。我们使用带有 Bonferroni 校正的事后 Dunn 检验的 Kruskal-Wallis 检验和 Fisher 精确检验进行比较，使用 Spearman 秩检验进行相关性分析，并使用多元线性回归进行多变量分析。
分析了330例已故线粒体疾病患者的数据（191例[57.9%]为儿童）。在肝脑综合征（中位数0.3，四分位间距[IQR]0.2 - 0.6年）和线粒体心肌病（中位数0.3，IQR 0.2 - 5.2年）中观察到最短的生存时间，而在慢性进行性眼外肌麻痹加征（中位数26.5，IQR 22.8 - 40.2年）和感觉性共济失调性神经病、构音障碍和眼肌麻痹（中位数21.0，IQR 13.8 - 28.5年）中观察到最长的生存时间。呼吸衰竭和肺部感染是与死亡相关的最常见病症（分别为52/330，15.7%和46/330，13.9%）。儿童（57/191，29.8%）比成人（12/139，8.6%，<0.001）更常需要无创通气，鼻胃管或胃管使用情况也是如此（儿童为131/191，68.6%，成人 为39/139，28.1%，<0.001）。在多变量分析中，患有运动障碍和核基因受累的个体使用任何呼吸支持的几率增加（分别为OR 2.42（95%CI 1.17 - 5.22）和OR 2.39（95%CI 1.16 - 5.07））。
这项国际合作突出了呼吸护理和感染管理的重要性，并为不同线粒体疾病的预后提供了参考。
