Characterization of Factors Associated With Death in Deceased Patients With Mitochondrial Disorders: A Multicenter Cross-Sectional Survey.

作者信息

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

机构信息

Epilepsy Center, Cleveland Clinic, OH.

Department of Neurology, Boston Children's Hospital, MA.

出版信息

Neurology. 2025 Feb 25;104(4):e209779. doi: 10.1212/WNL.0000000000209779. Epub 2025 Jan 30.

DOI:10.1212/WNL.0000000000209779

PMID:39883904

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11781783/

Abstract

BACKGROUND AND OBJECTIVES

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.

METHODS

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.

RESULTS

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).

DISCUSSION

This international collaboration highlights the importance of respiratory care and infection management and provides a reference for prognostication across different mitochondrial disorders.

摘要