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

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

Alina Ivaniuk  1 , Irina A Anselm  2 , Aaron Bowen  2 , Bruce H Cohen  3 , Fatma Tuba Eminoglu  4 , Jane Estrella  5 , Renata C Gallagher  6 , Rebecca D Ganetzky  7 , Jennifer Gannon  8 , Grainne S Gorman  9 , Carol Greene  10 , Andrea L Gropman  11 , Richard H Haas  12 , Michio Hirano  13 , Seema Kapoor  14 , Amel Karaa  15 , Mary Kay Koenig  16 , Cornelia Kornblum  17 , Engin Kose  4 , Austin Larson  18 , Uta Lichter-Konecki  19 , Piervito Lopriore  20 , Michelangelo Mancuso  20 , Robert McFarland  9 , Aye Myat Moe  9 , Eva Morava  21 , Yi Shiau Ng  9 , Russell P Saneto  22 , Fernando Scaglia  23 , Carolyn M Sue  24 , Mark Tarnopolsky  25 , Melissa A Walker  26 , Sumit Parikh  27 ; as the Hong Kong Mitochondrial Diseases Interest Group; Fung Cheuk-Wing  28 , Tsz-Sum Wong  29 , Kiran Belaramani  30 , Chun-Kong Chan  31 , Wing-Ki Chan  29 , Wai-Lun Larry Chan  32 , Hon-Wing Cheung  31 , Ka-Yin Cheung  31 , Shek-Kwan Chang  33 , Sing-Ngai Cheung  34 , Tsz-Fung Cheung  31 , Yuk-Fai Cheung  35 , Shuk-Ching Josephine Chong  36 , Chi-Kwan Jasmine Chow  37 , Hon-Yin B Chung  38 , Sin-Ying Florence Fan  39 , Wai-Ming Joshua Fok  40 , Ka-Wing Fong  35 , Tsui-Hang Sharon Fung  41 , Kwok-Fai Hui  31 , Ting-Hin Hui  31 , Joannie Hui  30 , Chun Hung Ko  42 , Min-Chung Kwan  34 , Mei-Kwan Anne Kwok  30 , Sung-Shing Jeffrey Kwok  43 , Moon-Sing Lai  44 , Yau-On Lam  31 , Ching-Wan Lam  45 , Ming-Chung Lau  46 , Chun-Yiu Eric Law  47 , Hiu-Fung Law  30 , Wing-Cheong Lee  48 , Han-Chih Hencher Lee  49 , Kin-Hang Leung  35 , Kit-Yan Leung  29 , Siu-Hung Li  44 , Tsz-Ki Jacky Ling  47 , Kam-Tim Timothy Liu  48 , Fai-Man Lo  50 , Colin Lui  51 , Ching-On Luk  35 , Ho-Ming Luk  52 , Che-Kwan Ma  46 , Karen Ma  39 , Kam-Hung Ma  53 , Yuen-Ni Mew  31 , Alex Mo  41 , Sui-Fun Hg  29 , Wing-Kit Grace Poon  54 , Bun Sheng  55 , Cheuk-Ling Charing Szeto  31 , Shuk-Mui Tai  48 , Jing-Liang Tang  31 , Choi-Ting Alan Tse  40 , Li-Yan Lilian Tsung  48 , Ho-Ming June Wong  56 , Wing-Yin Winnie Wong  56 , Kwok-Kui Wong  40 , Suet-Na Sheila Wong  30 , Chun-Nei Virginia Wong  38 , Wai-Shan Sammy Wong  57 , Chi-Kin Felix Wong  47 , Shun-Ping Wu  37 , Hiu-Fung Jerome Wu  55 , Man-Mut Yau  58 , Kin-Cheong Eric Yau  29 , Wai-Lan Yeung  30 , Hon-Ming Jonas Yeung  32 , Kin-Keung Edwin Yip  59 , Hui-Jun Wu  30 , Pui-Hong Terence Young  59 , Gao Yuan  33 , Yuet-Ping Liz Yuen  60 , Chi-Lap Yuen  61
Affiliations
Observational Study

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

Alina Ivaniuk et al. Neurology. .

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%, p < 0.001), as was nasogastric or gastric tube (131/191, 68.6% in children and 39/139, 28.1% in adults, p < 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.

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Conflict of interest statement

A. Ivaniuk, I.A. Anslem, A. Bowen, B.H. Cohen, F.T. Eminoglu, J. Estrella, and R.C. Gallagher report no relevant conflicts of interest. R.D. Ganetzky is a consultant for Minovia Therapeutics and Nurture Medical Genomics. J. Gannon, G.S. Gorman, C. Greene, A.L. Gropman, R.H. Haas, M. Hirano, S. Kapoor, A. Karaa, M.K. Koenig, C. Kornblum, E. Kose, A. Larson, U. Lichter-Konecki, P. Lopriore, M. Mancuso, R. McFarland, A.M. Moe, E. Morava, and Y.S. Ng report no relevant conflicts of interest. R.P. Saneto serves as a DSMB Board member for Reata and Reneo Pharmaceuticals, a site PI for various clinical trials, including those by PTC Pharmaceuticals, Stealth Biotherapeutics, Astellas Pharmaceuticals, and Reneo Pharmaceuticals, and is involved in NIH studies NIH 5U54NS078059-09 and RO1-FDA005404. F. Scaglia and C.M. Sue report no relevant conflicts of interest. M. Tarnopolsky is CEO of Exerkine Corporation, has speaker honoraria and advisory board duties for Sanofi-Genzyme, and served on a DSMB and eligibility criteria committee for Reneo Therapeutics. M.A. Walker is an author on US Provisional Patent Application 63/034,740, filed June 4, 2020, is a recipient of research funding from NIH/NINDS K08NS117889 and NIH/NHGRI U01HG007690 Center for Integrated Approaches to Undiagnosed Diseases, and is an honoraria recipient from the American Academy of Neurology. S. Parikh reports no relevant conflicts of interest. F. Cheuk-Wing and the members of the Hong Kong Mitochondrial Disease Interest Group report no relevant conflicts of interest. Go to Neurology.org/N for full disclosures.

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References

    1. Gorman GS, Schaefer AM, Ng Y, et al. . Prevalence of nuclear and mitochondrial DNA mutations related to adult mitochondrial disease. Ann Neurol. 2015;77(5):753-759. doi:10.1002/ana.24362 - DOI - PMC - PubMed
    1. DiMauro S, Schon EA, Carelli V, Hirano M. The clinical maze of mitochondrial neurology. Nat Rev Neurol. 2013;9(8):429-444. doi:10.1038/nrneurol.2013.126 - DOI - PMC - PubMed
    1. Parikh S, Goldstein A, Karaa A, et al. . Patient care standards for primary mitochondrial disease: a consensus statement from the Mitochondrial Medicine Society. Genet Med. 2017;19(12):1380-1397. doi:10.1038/gim.2017.107 - DOI - PMC - PubMed
    1. Rahman S, Blok RB, Dahl H‐HM, et al. . Leigh syndrome: clinical features and biochemical and DNA abnormalities. Ann Neurol. 1996;39(3):343-351. doi:10.1002/ana.410390311 - DOI - PubMed
    1. Parikh S, Karaa A, Goldstein A, et al. . Diagnosis of “possible” mitochondrial disease: an existential crisis. J Med Genet. 2019;56(3):123-130. doi:10.1136/jmedgenet-2018-105800 - DOI - PubMed

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