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Familial acute necrotizing encephalopathy(ANE; IIAE3)

MedGen UID:
382634
Concept ID:
C2675556
Finding
Synonyms: Encephalopathy, acute, infection-induced, 3, suceptibility to; Infection-induced Acute Encephalopathy 3, Susceptibility to; Susceptibility to Acute Necrotizing Encephalopathy 1
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): RANBP2 (2q13)
 
Monarch Initiative: MONDO:0011953
OMIM®: 608033
Orphanet: ORPHA88619

Definition

Acute necrotizing encephalopathy type 1, also known as susceptibility to infection-induced acute encephalopathy 3 or IIAE3, is a rare type of brain disease (encephalopathy) that occurs following a viral infection such as the flu.

Acute necrotizing encephalopathy type 1 typically appears in infancy or early childhood, although some people do not develop the condition until adolescence or adulthood. People with this condition usually show typical symptoms of an infection, such as fever, cough, congestion, vomiting, and diarrhea, for a few days. Following these flu-like symptoms, affected individuals develop neurological problems, such as seizures, hallucinations, difficulty coordinating movements (ataxia), or abnormal muscle tone. Eventually, most affected individuals go into a coma, which usually lasts for a number of weeks. The condition is described as "acute" because the episodes of illness are time-limited.

People with acute necrotizing encephalopathy type 1 develop areas of damage (lesions) in certain regions of the brain. As the condition progresses, these brain regions develop swelling (edema), bleeding (hemorrhage), and then tissue death (necrosis). The progressive brain damage and tissue loss results in encephalopathy.

Approximately one-third of individuals with acute necrotizing encephalopathy type 1 do not survive their illness and subsequent neurological decline. Of those who do survive, about half have permanent brain damage due to tissue necrosis, resulting in impairments in walking, speech, and other basic functions. Over time, many of these skills may be regained, but the loss of brain tissue is permanent. Other individuals who survive their illness appear to recover completely.

It is estimated that half of individuals with acute necrotizing encephalopathy type 1 are susceptible to recurrent episodes and will have another infection that results in neurological decline; some people may have numerous episodes throughout their lives. Neurological function worsens following each episode as more brain tissue is damaged. [from MedlinePlus Genetics]

Clinical features

From HPO
Cerebral edema
MedGen UID:
2337
Concept ID:
C0006114
Pathologic Function
Abnormal accumulation of fluid in the brain.
Coma
MedGen UID:
1054
Concept ID:
C0009421
Disease or Syndrome
The complete absence of wakefulness and consciousness, which is evident through a lack of response to any form of external stimuli.
Gliosis
MedGen UID:
4899
Concept ID:
C0017639
Pathologic Function
Gliosis is the focal proliferation of glial cells in the central nervous system.
Tetraplegia
MedGen UID:
19617
Concept ID:
C0034372
Disease or Syndrome
Paralysis of all four limbs, and trunk of the body below the level of an associated injury to the spinal cord. The etiology of quadriplegia is similar to that of paraplegia except that the lesion is in the cervical spinal cord rather than in the thoracic or lumbar segments of the spinal cord.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Encephalopathy
MedGen UID:
39314
Concept ID:
C0085584
Disease or Syndrome
Encephalopathy is a term that means brain disease, damage, or malfunction. In general, encephalopathy is manifested by an altered mental state.
Spastic tetraplegia
MedGen UID:
98433
Concept ID:
C0426970
Disease or Syndrome
Spastic paralysis affecting all four limbs.
Increased CSF protein concentration
MedGen UID:
329971
Concept ID:
C1806780
Finding
Increased concentration of protein in the cerebrospinal fluid.
Hypertonia
MedGen UID:
10132
Concept ID:
C0026826
Finding
A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move.
Pneumonia
MedGen UID:
10813
Concept ID:
C0032285
Disease or Syndrome
Inflammation of any part of the lung parenchyma.
Abnormality of the immune system
MedGen UID:
867388
Concept ID:
C4021753
Pathologic Function
An abnormality of the immune system.

Professional guidelines

PubMed

He L, Xu R, Wang J, Zhang L, Zhang L, Zhou F, Dong W
BMC Neurol 2019 Nov 13;19(1):285. doi: 10.1186/s12883-019-1522-0. PMID: 31722675Free PMC Article
Venketasubramanian N, Pwee KH, Chen CP; Singapore Ministry of Health Clinical Practice Guidelines Workgroup on Stroke and Transient Ischaemic Attacks
Int J Stroke 2011 Jun;6(3):251-8. doi: 10.1111/j.1747-4949.2011.00602.x. PMID: 21557813
Frizzell JP
AACN Clin Issues 2005 Oct-Dec;16(4):421-40; quiz 597-8. doi: 10.1097/00044067-200510000-00002. PMID: 16269890

Recent clinical studies

Etiology

Iyer G, Utage P, Bailur S, Utage A, Srirambhatla A, Hasan Q
J Child Neurol 2020 May;35(6):393-397. Epub 2020 Feb 26 doi: 10.1177/0883073820902308. PMID: 32102593

Diagnosis

Levine JM, Ahsan N, Ho E, Santoro JD
Mult Scler Relat Disord 2020 Aug;43:102194. Epub 2020 May 15 doi: 10.1016/j.msard.2020.102194. PMID: 32426208Free PMC Article
Iyer G, Utage P, Bailur S, Utage A, Srirambhatla A, Hasan Q
J Child Neurol 2020 May;35(6):393-397. Epub 2020 Feb 26 doi: 10.1177/0883073820902308. PMID: 32102593
Lee YJ, Hwang SK, Lee SM, Kwon S
Brain Dev 2017 Aug;39(7):625-628. Epub 2017 Mar 21 doi: 10.1016/j.braindev.2017.02.005. PMID: 28336122Free PMC Article
Nishimura N, Higuchi Y, Kimura N, Nozaki F, Kumada T, Hoshino A, Saitoh M, Mizuguchi M
Pediatr Int 2016 Nov;58(11):1215-1218. doi: 10.1111/ped.13119. PMID: 27882739
Denier C, Balu L, Husson B, Nasser G, Burglen L, Rodriguez D, Labauge P, Chevret L
J Neurol Sci 2014 Oct 15;345(1-2):236-8. Epub 2014 Jul 18 doi: 10.1016/j.jns.2014.07.025. PMID: 25128471

Therapy

Park YJ, Hwang JY, Kim YW, Lee YJ, Ko A
Medicine (Baltimore) 2021 Mar 26;100(12):e25171. doi: 10.1097/MD.0000000000025171. PMID: 33761695Free PMC Article
Soriano-Ramos M, Navarro-Abia V, Enamorado NN, Camacho-Salas A, De Aragón AM, García-Hoyos M, de Las Heras RS
Clin Neurol Neurosurg 2018 Nov;174:134-136. Epub 2018 Sep 11 doi: 10.1016/j.clineuro.2018.09.014. PMID: 30241006

Prognosis

Ayaz A, Doğru Z, Kılıç B, Süzek BE
Clin Neurol Neurosurg 2022 Oct;221:107418. Epub 2022 Aug 23 doi: 10.1016/j.clineuro.2022.107418. PMID: 36029610
Park YJ, Hwang JY, Kim YW, Lee YJ, Ko A
Medicine (Baltimore) 2021 Mar 26;100(12):e25171. doi: 10.1097/MD.0000000000025171. PMID: 33761695Free PMC Article
Levine JM, Ahsan N, Ho E, Santoro JD
Mult Scler Relat Disord 2020 Aug;43:102194. Epub 2020 May 15 doi: 10.1016/j.msard.2020.102194. PMID: 32426208Free PMC Article
Lee YJ, Hwang SK, Lee SM, Kwon S
Brain Dev 2017 Aug;39(7):625-628. Epub 2017 Mar 21 doi: 10.1016/j.braindev.2017.02.005. PMID: 28336122Free PMC Article
Nishimura N, Higuchi Y, Kimura N, Nozaki F, Kumada T, Hoshino A, Saitoh M, Mizuguchi M
Pediatr Int 2016 Nov;58(11):1215-1218. doi: 10.1111/ped.13119. PMID: 27882739

Clinical prediction guides

Denier C, Balu L, Husson B, Nasser G, Burglen L, Rodriguez D, Labauge P, Chevret L
J Neurol Sci 2014 Oct 15;345(1-2):236-8. Epub 2014 Jul 18 doi: 10.1016/j.jns.2014.07.025. PMID: 25128471

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