Familial acute necrotizing encephalopathy with RANBP2 mutation: The first report in Northeast Asia

Abstract

Background: Acute necrotizing encephalopathy (ANE) is a rare but rapidly progressing encephalopathy following a febrile illness, commonly a viral infection. It is characterized by the features of acute encephalopathy such as seizure, alteration of consciousness, and symmetric involvement of the bilateral thalamus on neuroimaging tests. Although most ANE cases have occurred sporadically, familial or recurrent ANE has been reported in Caucasian patients, with genetic susceptibility to ANE noted in some patients due to a RANBP2 mutation. We report the cases of two Korean siblings with typical ANE and RANBP2 mutation.

Case report: A 2year-old Korean girl presented with prolonged seizures and encephalopathy after two days of febrile illness. Brain computed tomography (CT) showed diffuse brain swelling and low attenuation in the bilateral thalamus. Two months later, her younger sister presented with lethargy and flurries of seizures after a Mycoplasma pneumoniae infection. Brain magnetic resonance imaging scan (MRI) showed a characteristic involvement of the bilateral thalamus, suggesting ANE. Although they received intravenous steroids and immunoglobulin, the older child died; her sister remained in a coma. Both were diagnosed with familial ANE after identifying a common missense mutation in RANBP2 (c.1754C>T: p.Thr585Met) in the younger sister and their father.

Conclusions: This report is the first case of familial ANE in Northeast Asia identifying a RANBP2 mutation with poor outcome. Due to rapidly deterioration and recurrent nature of familial ANE, genetic test of RANBP2 mutation should be considered for early diagnosis. Further studies are needed to elucidate the nature of ANE.

Keywords: Acute necrotizing encephalopathy; Familial; RANBP2.

Fig. 1

Brain CT of Case 1. Axial (A) and coronal (B) non-contrast CT shows low attenuation in the bilateral thalamus (arrowhead) and diffuse effacement of the sulci and lateral ventricles, indicating diffuse cerebral edema.

Fig. 2

Brain MRI of Case 2. Fluid attenuated inversion recovery images (A, B) reveal hyperintense signal changes in the bilateral thalamus, external/extreme capsule, brainstem tegmentum, and mammillary bodies as well as multifocal foci in cerebral and cerebellar white matter. Diffusion-weighted images (C, D) show diffusion restrictions in the bilateral thalamus and mammillary bodies.

Fig. 3

Sequencing electropherograms of RANBP2-specific cDNA reveals a c.1754C > T mutation in the patient from case 2 and the father, but not in the mother. We could not perform genetic analysis on the patient from case 1 (deceased).