Natural History of Leigh Syndrome: A Study of Disease Burden and Progression. Issue 1 (12th November 2021)

• Record Type: Journal Article
• Authors: Lim, Albert Z.; Ng, Yi Shiau; Blain, Alasdair; Jiminez‐Moreno, Cecilia; Alston, Charlotte L.; Nesbitt, Victoria; Simmons, Louise; Santra, Saikat; Wassmer, Evangeline; Blakely, Emma L.; Turnbull, Doug M.; Taylor, Robert W.; Gorman, Gráinne S.; McFarland, Robert
• Is Part Of: Annals of neurology. Volume 91:Issue 1(2022)
• Page Start: 117
• Page End: 130
• Publication Date: 2021-11-12
• Subjects: Neurology -- Periodicals; Pediatric neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; 616.8
• DOI: 10.1002/ana.26260
• Languages: English
• ISSNs: 0364-5134

Abstract

Abstract : 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 ( τ b ≈ 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 2022;91:117–130