Dominant encephalopathy mimicking mitochondrial disease

Abstract

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. ### Patients. We included 6 patients with ANE in 3 generations (figure, G). ANE was recurrent in patients 2 and 5. Five of the episodes appeared in infancy, …