Familial acute necrotizing encephalopathy without RANBP2 mutation: Poor outcome

Area of Science:

• Neurology
• Genetics
• Pediatrics

Background:

• Acute necrotizing encephalopathy (ANE) is a rare neurological disorder primarily affecting children.
• While often sporadic, ANE can present as a familial or recurrent condition, particularly in Caucasian populations.
• Mutations in the RAN-binding protein 2 (RANBP2) gene are identified in over half of familial/recurrent ANE cases, but not previously reported in East Asia.

Observation:

• This study reports the first sibling cases of typical ANE in Japan, both experiencing poor outcomes.
• Genetic analysis, including RANBP2 and carnitine palmitoyl transferase II (CPT2) genes, revealed no causative mutations or disease-related polymorphisms in these patients.
• Literature review indicates that familial or recurrent ANE cases lacking RANBP2 mutations exhibit more severe outcomes and a higher prevalence in males.

Findings:

• The absence of RANBP2 mutations in these Japanese sibling cases of ANE highlights a potential East Asian-specific genetic etiology.
• The observed severe outcomes in familial/recurrent ANE without RANBP2 mutations suggest the involvement of other unidentified genetic factors.

Implications:

• These findings suggest that genetic factors beyond RANBP2 mutations are implicated in familial or recurrent ANE.
• Further research is warranted to identify novel gene mutations responsible for ANE, particularly in East Asian populations.
• Understanding the genetic basis of ANE is crucial for improved diagnosis, prognosis, and potential therapeutic strategies.