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. Pediatrics 2010;125: e693–e698

Acute Necrotizing Encephalopathy: An Underrecognized Clinicoradiologic Disorder

“…The missense mutations in the gene encoding the nuclear pore protein Ran Binding Protein 2 ( RANBP2 ) were found to be the susceptibility alleles for familial and recurrent cases of ANE, and they proposed naming this type of ANE as “ANE1” [ 50 ]. Since the relationship between ANE and the RANBP2 gene was identified, there have been several reports on recurrent or familial cases, while the mechanism of this mutation leading to pathology remains unclear [ 20 , 22 , 51 ]. RANBP2 is located on the cytoplasmic surface of the nuclear pore, and its numerous functions throughout the cell cycle have been found, which include facilitation of the protein transportation and sumoylation of protein cargoes during interphase, intracellular trafficking, or energy maintenance in certain type of cells, including neurons, and contribution to the nuclear envelop breakdown as well as facilitation of sister chromatid resolution during mitosis [ 50 ].…”

Acute necrotising encephalopathy in a child with H1N1 influenza infection: a clinicoradiological diagnosis and follow-up

“…It occurs sporadically in previously healthy infants and children less than 11 years of age 10. Recurrences have been reported in children with mutations in RAN-binding protein two gene 11.…”

Acute necrotizing encephalopathy associated with novel influenza H1N1 (pdm09) infection: MRI and correlation with brain necropsy

“…Thalamic signal abnormality Other sites of involvement include brain stem tegmentum, periventricular white matter, capsular white matter, putamen and cerebellum [4]. Hemorrhagic signal related to coagulative necrosis prior to cavitation has been known to occur in the central component of affected deep grey matter, most notably the thalamic [1][2][3][4][5][6][7][8][9][10][11][12][13]. Post-contrast sequences acquired following administration of intravenous gadolinium demonstrate ring enhancement around the hemorrhagic areas.…”