Dominant encephalopathy mimicking mitochondrial disease

The hallmark of acute necrotizing encephalopathy (ANE) is multiple, symmetric brain lesions.¹ ANE is triggered by a viral infection in previously healthy children. The presenting symptoms are coma, convulsions, vomiting, hyperpyrexia, and hepatomegaly. Recently a dominant mutation (c.1880C→T, p.Thr585Met) in the gene encoding the nuclear pore protein Ran Binding Protein 2 (RANBP2) has been reported in familial, recurrent ANE (ANE1).² In isolated ANE the typical brain lesions are located in the thalami bilaterally, putamina, deep periventricular white matter, cerebellum, and brainstem,^3,4 while in ANE1 the MRI changes are seen in the external capsules, claustrum, limbic structure, or temporal lobes.² Hepatic involvement is common in Asian patients with ANE, but not in ANE1.² Differential diagnosis of ANE includes mitochondrial disorders, especially Leigh/Alpers syndrome,⁵ inflammatory, demyelinating brain diseases, acute disseminating encephalomyelitis (ADEM), or even multiple sclerosis (MS).⁶

We report the clinical, MRI, and molecular genetic findings of ANE in a 3-generation family, and discuss the differential diagnosis.