Acute necrotizing encephalopathy in 3 brothers

Abstract

Acute necrotizing encephalopathy (ANE) is a devastating and rapidly progressive neurologic disorder that occurs in healthy children after common viral infections. Typically, ANE is sporadic and does not recur. However, familial (ANE1) and recurrent cases have been reported and were recently linked to mutations in RANBP2 (RAN-binding protein 2). We report here a multiply affected kindred with recurrent familial ANE. These affected male siblings (a set of twins and their older brother) all presented with prodromal fever and upper respiratory tract infection that progressed within 72 hours to seizures, coma, and ultimately death, a course that is typical of ANE. It should be noted that 1 brother was treated with early aggressive management, including corticosteroids, and he survived for an additional 5 years. This represents the second reported case of familial ANE in the United States and the only case of male siblings with consanguineous parents. We hope that early recognition and growing awareness can lead to more effective treatment and better outcomes in the future.

FIGURE 1

A–D, Cranial CT imaging: A, initial CT of patient 1; B, initial CT of patient 2; C, 8-hour CT of patient 3; D, 24-hour CT of patient 3. E–H, Cranial MRI of patient 3, day 7 (E–G, T2-weighted fluid-attenuated inversion-recovery MRI; H, diffusion-weighted MRI). The arrows indicate injury; , thalamus; , putamen; ➡ (C), caudate; , cerebellar nuclei; , dorsal brainstem; (F), white matter.