Recurrent acute necrotizing encephalopathy in a boy with RANBP2 mutation and thermolabile CPT2 variant: The first case of ANE1 in Japan

Ohashi, Eri; Hayakawa, Isao; Murofushi, Yuka; Kawai, Michiko; Suzuki-Muromoto, Sato; Abe, Yuichi; Yoshida, Michiko; Kono, Naoko; Kosaki, Rika; Hoshino, Ai; Mizuguchi, Masashi; Kubota, Masaya

doi:10.1016/j.braindev.2021.04.009

Cited by 11 publications

(9 citation statements)

References 21 publications

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“…Mendelian inheritance, given the low penetrance (40-50%) of ANE1 (an autosomal dominantly inherited disorder caused by a gene mutation) in which the involvement of other genetic (thermolabile variants of a mitochondrial enzyme) and environmental factors (influenza virus) are described (Neilson et al, 2003;Neilson et al, 2004;Ohashi et al, 2021).…”

Section: Acute Encephalopathy As a Complex Disordermentioning

confidence: 99%

Genetic and environmental risk factors of acute infection-triggered encephalopathy

et al. 2023

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Acute encephalopathy is a constellation of syndromes in which immune response, metabolism and neuronal excitation are affected in a variable fashion. Most of the syndromes are complex disorders, caused or aggravated by multiple, genetic and environmental risk factors. Environmental factors include pathogenic microorganisms of the antecedent infection such as influenza virus, human herpesvirus-6 and enterohemorrhagic Escherichia coli, and drugs such as non-steroidal anti-inflammatory drugs, valproate and theophylline. Genetic factors include mutations such as rare variants of the SCN1A and RANBP2 genes, and polymorphisms such as thermolabile CPT2 variants and HLA genotypes. By altering immune response, metabolism or neuronal excitation, these factors complicate the pathologic process. On the other hand, some of them could provide promising targets to prevent or treat acute encephalopathy.

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Section: Acute Encephalopathy As a Complex Disordermentioning

confidence: 99%

Genetic and environmental risk factors of acute infection-triggered encephalopathy

et al. 2023

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“…Patient 14 had a recurrent episode, and his half‐brother died of the same disease. Genetic testing of Patient 14 and his father revealed that they were heterozygous for a missense mutation (c.1754C>T, exon 12) in RANBP2 on chromosome 2, which is a hotspot mutation (Denier et al, 2014; Gilson et al, 2011; Lee et al, 2017; Ohashi et al, 2021; Park et al, 2021; Singh et al, 2015). The minor allele frequency was 0.00012 (exac).…”

Section: Discussionmentioning

confidence: 99%

Clinical features and imaging manifestations of acute necrotizing encephalopathy in children

Peng

Jiang

et al. 2022

Intl J of Devlp Neuroscience

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We summarized the clinical features of acute necrotizing encephalopathy (ANE) in children.Methods: Clinical data of 14 children with ANE at one center from January 2017 to January 2020 were retrospectively analyzed. ANE severity score (ANEss) was used to assess ANE severity, and the Glasgow Outcome Scale-Extended was used to assess functional outcomes.Results: Peak incidence was between 1 and 3 years of age (71%), and a large percentage of males were affected (79%). The main manifestations included fever (100%), seizure (86%), and impaired consciousness (100%). Seven patients (58%) developed status epilepticus. The etiology was identified in 10 patients (71%) and mainly included H1N1 (36%) and Epstein-Barr virus (29%).Complications included multiple organ failure (MOF), predominantly liver (36%), heart (21%) and kidney (7%) failure, gastrointestinal hemorrhage (21%), hypernatremia (7%), hematuria (7%), disseminated intravascular coagulation (7%), and shock (7%). Pleocytosis was observed in two patients, and increased cerebrospinal fluid protein was found in 11 patients. A missense mutation in RANBP2 (c.1754C>T: p.Thr585Met) was observed in one patient. Magnetic resonance imaging revealed increased T2 and T1 signal density in multifocal and symmetric brain lesions (bilateral thalami, 100%) in all patients during the acute phase. There were no deaths. Nine children retained neurological sequelae affecting movement, cognition, speech, vision, and/or seizure. Four children recovered almost completely. There was a significant correlation between risk classification and outcome by ANE-ss. Conclusion:ANE is a group of clinical and imaging syndromes. Most patients have severe neurological sequelae, and ANE may have lower mortality. And ANE-ss can assess prognosis.

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“…RANBP2 gene mutations are generally thought to be limited to patients with Caucasian ethnicity. Recently, several ANE patients with RANBP2 gene mutations have been reported in Asian populations ( 22 ), suggesting that race may not be a significant associated factor for the occurrence of ANE. It has also been reported that carnitine palmitoyl transferase II polymorphism is linked with the pathogenesis of ANE ( 23 ).…”

Section: Discussionmentioning

confidence: 99%

Clinical evaluation of acute necrotizing encephalopathy in children

Fan

Huang

et al. 2022

Front. Pediatr.

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ObjectiveAcute necrotizing encephalopathy (ANE) is a rare but severe encephalopathy and is associated with a high morbidity and mortality. We aimed to analyze and compare the clinical features and predictive indicators of pediatric ANE.Materials and methodsThis retrospective study included children with ANE diagnosed at Guangzhou Women and Children’s Medical Center between November 2018 and January 2020. Pediatric patients’ information, including clinical characteristics, laboratory tests, neuroelectrophysiology and brain magnetic resonance imaging (MRI) findings, MRI score, brainstem auditory evoked potential (BAEP) grades, ANE severity scores (ANE-SS), and modified Rankin scale (mRS), were collected.ResultsTwelve ANE patients were included. Among them, one patient (8.3%) died from brainstem dysfunction, one (8.3%) recovered and 10 (83.3%) experienced neurological sequelae. All patients had an initial viral infection and neurological symptoms such as acute disturbance of consciousness (ADOC) or seizure, and the interval from onset of the disease to neurological manifestations was 3 (1.25–3) days. MRI score-I ranged from 1 to 3 (1.8 ± 0.7), MRI score-II ranged from 1 to 4 (2.5 ± 1.1). ANE-SS varied from 1 to 6 (3.9 ± 1.3). The scores of mRS were from 0 to 6 (2.9 ± 1.7). Higher MRI score were associated with worse outcomes, while the BAEP grade and ANE-SS score were not significantly associated with mRS.ConclusionANE is a severe encephalopathy syndrome with rapid progression, resulting in serious neurological sequelae. Compared with BAEP grade and ANE-SS, brain MRI shows more comprehensive advantages in predicting the prognosis of ANE patients. More in-depth research and better indicators are still needed to support the evaluation and treatment of ANE.

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Recurrent acute necrotizing encephalopathy in a boy with RANBP2 mutation and thermolabile CPT2 variant: The first case of ANE1 in Japan

Cited by 11 publications

References 21 publications

Genetic and environmental risk factors of acute infection-triggered encephalopathy

Genetic and environmental risk factors of acute infection-triggered encephalopathy

Clinical features and imaging manifestations of acute necrotizing encephalopathy in children

Clinical evaluation of acute necrotizing encephalopathy in children

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