Highlights
- •Infection-induced acute encephalopathy-3 (IIAE3) is due to mutation in RANBP2.
- •We report a new autosomal dominant acute necrotizing encephalopathy IIAE3 family.
- •Our cases illustrate both the incomplete penetrance and possibly lethal phenotype.
- •Differential diagnosis includes Leigh syndrome, multiple sclerosis and ADEM.
- •DNA-based diagnosis is important to adopt prophylaxis and symptomatic treatment.
Abstract
Background
Acute necrotizing encephalopathy (ANE) is a rare and severe parainfectious central
nervous system disease in which previously healthy children develop rapidly progressive
coma following viral illness. While most ANE are sporadic, familial autosomal dominant
ANE due to mutations in the RANBP2 gene has been recently reported (ANE1 or infection-induced
acute encephalopathy-3 (IIAE3)). To date, only few IIAE3 families with ADANE episodes
have been described.
Objective
To report a new family with ADANE, describe clinical and radiological features and
discuss differential diagnosis including Leigh syndrome or multiple sclerosis.
Observation
The family included 3 symptomatic individuals and one 59 year-old asymptomatic obligate carrier. Patients presented acute episodes of encephalopathy
few days after common viral infection. Ages of onset ranged from 6 months to 5 years. Episodes not only occurred in childhood but also recurred in adulthood. Initial
neurological signs included coma, focal neurological deficits and seizures. MRI showed
typical necrotizing lesions primarily in the thalamus and brainstem, and in the temporal
lobes and insula. CSF cell count and cultures were normal during episodes. RANBP2 gene screening identified pathogenic heterozygous c.1754C>T mutation (p.Thr585Met).
Episodes led to cognitive or physical handicap in 2 patients and were fatal in one
child.
Conclusion
IIAE3 or ADANE due to RANBP2 mutations has a large clinical heterogeneity. Our family illustrates the associated
phenotypes from asymptomatic carrier to severe episodes of encephalopathy. Based on
MRI features, the genetic IIAE3 diagnosis is important since prophylaxis and symptomatic
management of infections may be beneficial, possibly in association with steroid or
gammaglobulins.
Keywords
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Article info
Publication history
Published online: July 17, 2014
Accepted:
July 10,
2014
Received in revised form:
July 8,
2014
Received:
April 7,
2014
Footnotes
☆Financial disclosure statement: The authors have nothing to disclose.
Identification
Copyright
© 2014 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
