Natural History of Leigh Syndrome: A Study of Disease Burden and Progression.
Ann Neurol
; 91(1): 117-130, 2022 01.
Article
em En
| MEDLINE
| ID: mdl-34716721
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% â 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% â 57%), exclusive enteral feeding (22% â 46%), and one-to-one assistance for self-care (25% â 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;91117-130.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doença de Leigh
Tipo de estudo:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Child
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Child, preschool
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Female
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Humans
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Infant
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Male
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article