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Lookup NU author(s): Dr Albert Lim,
Dr Yi NgORCiD,
Dr Alasdair Blain,
Dr Cecilia Jimenez Moreno,
Dr Charlotte Alston,
Emeritus Professor Doug Turnbull,
Professor Robert Taylor,
Professor Grainne Gorman,
Professor Bobby McFarlandORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2021 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. Objective: This observational cohort study aims to quantify disease burden over time, establish disease progression rates, and identify factors that may determine the disease course of Leigh syndrome. Methods: Seventy-two Leigh syndrome children who completed the Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) at baseline at 3.7 years (interquartile range [IQR] = 2.0–7.6) and follow-up assessments at 7.5 years (IQR = 3.7–11.0) in clinics were enrolled. Eighty-two percent of this cohort had a confirmed genetic diagnosis, with pathogenic variants in the MT-ATP6 and SURF1 genes being the most common cause. The total NPMDS scores denoted mild (0–14), moderate (15–25), and severe (>25) disease burden. Detailed clinical, neuroradiological, and molecular genetic findings were also analyzed. Results: The median total NPMDS scores rose significantly (Z = −6.9, p < 0.001), and the percentage of children with severe disease burden doubled (22% → 42%) over 2.6 years of follow-up. Poor function (especially mobility, self-care, communication, feeding, and education) and extrapyramidal features contributed significantly to the disease burden (τb ≈ 0.45–0.68, p < 0.001). These children also deteriorated to wheelchair dependence (31% → 57%), exclusive enteral feeding (22% → 46%), and one-to-one assistance for self-care (25% → 43%) during the study period. Twelve children (17%) died after their last NPMDS scores were recorded. These children had higher follow-up NPMDS scores (disease burden; p < 0.001) and steeper increase in NPMDS score per annum (disease progression; p < 0.001). Other predictors of poor outcomes include SURF1 gene variants (p < 0.001) and bilateral caudate changes on neuroimaging (p < 0.01). Interpretation: This study has objectively defined the disease burden and progression of Leigh syndrome. Our analysis has also uncovered potential influences on the trajectory of this neurodegenerative condition. ANN NEUROL 2021.
Author(s): Lim AZ, Ng YS, Blain A, Jiminez-Moreno C, Alston CL, Nesbitt V, Simmons L, Santra S, Wassmer E, Blakely EL, Turnbull DM, Taylor RW, Gorman GS, McFarland R
Publication type: Article
Publication status: Published
Journal: Annals of Neurology
Print publication date: 01/01/2022
Online publication date: 30/10/2021
Acceptance date: 26/10/2021
Date deposited: 24/11/2021
ISSN (print): 0364-5134
ISSN (electronic): 1531-8249
Publisher: John Wiley and Sons Inc.
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