Clinical characteristics and long-term prognosis of 150 children with MELAS syndrome in China.

Abstract

Objective: The aim was to summarise the clinical characteristics of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), evaluate patient survival status, and identify prognostic factors.

Methods: This retrospective study enrolled 150 children with MELAS from 07/2004 to 07/2023. The patients were followed up for a median of 3.37 years (IQR: 2.07-6.16 years). Disease burden was assessed using the Newcastle Pediatric Mitochondrial Disease Scale (NPMDS), and Spearman's correlation coefficient was used to analyse factors affecting disease severity. The Kaplan-Meier and Cox proportional methods were used for survival analysis.

Results: Overall, 150 patients (73 male) were enrolled, of whom 118 were followed up and 22 died. The mean age at onset was 8.2 years (0.4-15.3), and stroke-like episodes were the most common initial symptoms (54%). Among the surviving patients, 78 completed the NPMDS (mean score: 23.6 ± 6.7 points), and 71.8% (56/78) had moderate-to-severe disease (NPMDS score ≥ 15 points). The NPMDS score was positively correlated with disease duration (r = 0.41, P < 0.001) and negatively correlated with age at onset (r =  -0.26, P < 0.01). Among 48 patients who received long-term oral L-arginine and anti-seizure medications (ASMs), 56.3% (27/48) experienced reductions in seizures and stroke-like episodes. The 10- and 15-year survival rates were 65.3% and 34.5%, respectively. Muscle weakness was an independent risk factor for death (HR = 4.83, 95% CI 1.32-17.68; P = 0.017).

Conclusions: This study had the largest cohort and longest follow-up of pediatric MELAS. Early onset was associated with severe disease, while muscle weakness was associated with a worse prognosis. Early identification and effective management of stroke-like episodes and seizures are crucial to reduce the disease burden.