Abstract
Objectives
Acute encephalopathy is an acute brain dysfunction after preceding infection, consisting
of multiple syndromes. Some syndromes, such as acute encephalopathy with biphasic
seizures and late reduced diffusion (AESD), are severe with poor outcome, whereas
others, such as clinically mild encephalitis/encephalopathy with reversible splenial
lesion (MERS), are mild with favorable outcome. Previous study reported the association
of the thermolabile polymorphism in Carnitine Palmitoyltransferase 2 (CPT2) gene and severe syndromes of acute encephalopathy. To further explore the pathogenetic
role of CPT2 in acute encephalopathy, we conducted a case-control association study
of a typical thermolabile CPT2 polymorphism, rs2229291, in 416 patients of acute encephalopathy, including both
severe and mild syndromes.
Methods
The case cohort consisted of 416 patients, including AESD, MERS, and other syndromes.
The control subjects were 100 healthy Japanese. rs2229291 was genotyped by Sanger
sequencing. Genetic distribution was compared between the patients and controls using
Cochran-Armitage trend test.
Results
Minor allele frequency of rs2229291 was significantly higher in AESD (p = 0.044), MERS (p = 0.015) and entire acute encephalopathy (p = 0.044) compared to the controls. The polymorphism showed no significant association
with influenza virus, or with outcome.
Conclusions
This study provided evidence that CPT2 is a susceptibility gene for overall acute encephalopathy, including both severe
and mild syndromes, and suggested that impairment of mitochondrial metabolism is common
to various syndromes of acute encephalopathy.
Keywords
- Carnitine palmitoyltransferase 2
- Thermolability
- Energy failure
- Acute encephalopathy
- Susceptibility gene
- Predisposing factor
- Genetic risk factor
- Clinically mild encephalitis/encephalopathy with reversible splenial lesion
- Acute encephalopathy with biphasic seizures and late reduced diffusion
- Acute necrotizing encephalopathy
- Acute encephalitis with refractory
- Repetitive partial seizures/febrile infection-related epileptic syndrome
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Brain and DevelopmentAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Acute encephalopathy associated with influenza and other viral infections.Acta Neurol Scand. 2007; 115: 45-56
- Epidemiology of acute encephalopathy in Japan, with emphasis on the association of viruses and syndromes.Brain Dev. 2012; 34: 337-343
- Carnitine palmitoyltransferase II (CPT II) deficiency: Genotype-Phenotype analysis of 50 patients.J Neurol Sci. 2014; 338: 107-111
- Thermolabile phenotype of carnitine palmitoyltransferase II variations as a predisposing factor for influenza-associated encephalopathy.FEBS Lett. 2005; 579: 2040-2044
- Thermal instability of compound variants of carnitine palmitoyltransferase II and impaired mitochondrial fuel utilization in influenza-associated encephalopathy.Hum Mutat. 2008; 29: 718-727
- Thermolabile CPT II variants and low blood ATP levels are closely related to severity of acute encephalopathy in Japanese children.Brain Dev. 2012; 34: 20-27
- Carnitine palmitoyl transferase II polymorphism is associated with multiple syndromes of acute encephalopathy with various infectious diseases.Brain Dev. 2011; 33: 512-517
- Cytokine-related and sodium channel polymorphism as candidate predisposing factors for childhood encephalopathy FIRES/AERRPS.J Neurol Sci. 2016; 368: 272-276
Team RDC, R Development Core Team R. R: A language and environment for statistical computing. R Found Stat Comput 2016;1:409.
Tomas A, Aragon J, Fay MP, Wollschlaeger D, Omidpanah A. Package ‘ epitools ’ R package version 0.5-10. https://CRAN.R-project.org/ 2017.
- Specific HLA genotypes confer susceptibility to acute necrotizing encephalopathy.Genes Immun. 2016; 17: 367-369
- Infection-triggered familial or recurrent cases of acute necrotizing encephalopathy caused by mutations in a component of the nuclear pore, RANBP2.Am J Hum Genet. 2009; 84: 44-51
- ADORA2A polymorphism predisposes children to encephalopathy with febrile status epilepticus.Neurology. 2013; 80: 1571-1576
- Hemiconvulsion-hemiplegia-epilepsy syndrome associated with CACNA1A S218L mutation.Pediatr Neurol. 2011; 45: 193-196
- De novo variants in RHOBTB2, an atypical Rho GTPase gene, cause epileptic encephalopathy.Hum Mutat. 2018; 39: 1070-1075
- An episode of acute encephalopathy with biphasic seizures and late reduced diffusion followed by hemiplegia and intractable epilepsy observed in a patient with a novel frameshift mutation in HNRNPU.Brain Dev. 2018; 40: 813-818
- MYRF is associated with encephalopathy with reversible myelin vacuolization.Ann Neurol. 2017; : 98-106
- Transient, recurrent, white matter lesions in X-linked Charcot-Marie-Tooth disease with heterozygote mutation of GJB1 gene: case report of a female patient (in Japanese).Rinsho Shinkeigaku (Tokyo). 2018; 58: 302-307
- Retrospective multiinstitutional study of the prevalence of early death in Dravet syndrome.Epilepsia. 2011; 52: 1144-1149
- Acute encephalopathy in children with Dravet syndrome.Epilepsia. 2012; 53: 79-86
- A CACNB4 mutation shows that altered Cav2.1 function may be a genetic modifier of severe myoclonic epilepsy in infancy.Neurobiol Dis. 2008; 32: 349-354
- Hemiconvulsion-hemiplegia syndrome in a patient with severe myoclonic epilepsy in infancy.Epilepsia. 2009; 50: 2158-2162
- Acute encephalopathy with a truncation mutation in the SCN1A gene: a case report.Epilepsia. 2010; 51: 1886-1888
- Genetic seizure susceptibility underlying acute encephalopathies in childhood.Epilepsy Res. 2010; 91: 143-152
- Mutations of the SCN1A gene in acute encephalopathy.Epilepsia. 2012; 53: 558-564
- Missense mutations in sodium channel SCN1A and SCN2A predispose children to encephalopathy with severe febrile seizures.Epilepsy Res. 2015; 117: 1-6
- Acute encephalopathy with a novel point mutation in the SCN2A gene.Epilepsy Res. 2012; 102: 109-112
- Clinical features and new molecular findings in Carnitine Palmitoyltransferase II (CPT II) deficiency.J Neurol Sci. 2008; 266: 97-103
- Drugs indicated for mitochondrial dysfunction as treatments for acute encephalopathy with onset of febrile convulsive status epileptics.J Neurol Sci. 2016; 360: 57-60
Article info
Publication history
Published online: July 24, 2019
Accepted:
July 10,
2019
Received in revised form:
June 10,
2019
Received:
March 28,
2019
Identification
Copyright
© 2019 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
