Acute necrotizing encephalopathy (ANE) is a rare disease that predominantly affects children and is associated with a high mortality rate. Here we report three cases of COVID-19-related ANE in children, with the mutation detection in two genes associated with mitochondrial dysfunction. The cases exhibited common ANE symptoms, such as fever, impaired consciousness, positive pathological reflex, increased cerebrospinal fluid protein, and multifocal and symmetric brain lesions identified through MRI. Using genotype-phenotype correlation analysis in trio-whole exome sequencing (WES), four potential pathogenic variants were identified in two genes associated with mitochondrial function (RANBP2 and MCCC2). Notably, MCCC2 was identified as being potentially associated with COVID-19-related ANE for the first time, and two of the four variants had not been previously reported. Our findings expand the clinical and mutation spectrum of COVID-19-related ANE in pediatric cases. The finding of these three new cases in our study further supports the previous hypothesis about the role of mitochondrial homeostatic imbalance in COVID-19-related ANE. It is essential to use genetic testing to identify this subset of patients with compromised mitochondrial function in order to improve patient management and prognosis.
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We would like to sincerely thank Professor Taosheng Huang for his invaluable advice and guidance in the writing and revision of the manuscript. We would also like to express our gratitude to all those who have provided assistance and support for our article.
This research was supported by the Natural Science Foundation of Fujian Province (Grant no. 2022J011097).
The authors declare no competing interests.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Wu, D., Zheng, Y., Li, Y. et al. Exploring the molecular and clinical spectrum of COVID-19-related acute necrotizing encephalopathy in three pediatric cases. J Hum Genet 68, 769–775 (2023). https://doi.org/10.1038/s10038-023-01171-z