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

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.