Clinical and genetic characteristics of RANBP2 mutations in children with acute necrotizing encephalopathy.

Background: This study investigated RANBP2 mutations in children with acute necrotizing encephalopathy (ANE) and conducted a systematic review of the differences in clinical characteristics between with or without RANBP2 mutations.

Methods: Whole-exome sequencing was performed on 19 pediatric ANE patients at Beijing Children's Hospital affiliated to Capital Medical University between 2017 and 2020. A systematic literature review was also conducted on the clinical characteristics and spectrum analysis of RANBP2 mutations.

Results: Besides the common mutation site c.1754 C > T, new mutation sites were identified, including c.7454G > T, c.7474 A > G, c.7807 C > T, c.7918 C > A, and c.872 A > G. These sites are highly conserved. Twenty-four publications describing 38 ANE children were reviewed, of which 22 cases had the RANBP2 mutations. When combined with our study, the data included 54 ANE children aged from 3 months to 120 months, and divided into RANBP2 mutation group (n = 26) and non-mutation group (n = 28). No significant differences were observed in initial presentations, neuroimaging, treatment, or outcomes between these two groups. However, children with RANBP2 mutations had slightly elevated blood ammonia levels and a broader etiological spectrum, especially involving non-influenza pathogens.

Conclusion: This study highlights novel RANBP2 mutation sites in ANE children and associates these mutations with higher blood ammonia levels and diverse etiologies.