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Article: Fatal viral infection-associated encephalopathy in two Chinese boys: A genetically determined risk factor of thermolabile carnitine palmitoyltransferase II variants

TitleFatal viral infection-associated encephalopathy in two Chinese boys: A genetically determined risk factor of thermolabile carnitine palmitoyltransferase II variants
Authors
KeywordsChinese
Coxsackie Virus
H1n1 Human Swine Influenza
Influenza-Associated Encephalopathy
Thermolabile Carnitine Palmitoyltransferase Ii
Viral Infection-Associated Encephalopathy
Issue Date2011
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/jhg/index.html
Citation
Journal Of Human Genetics, 2011, v. 56 n. 8, p. 617-621 How to Cite?
AbstractInfluenza-associated encephalopathy (IAE) is a potentially fatal neurological complication of influenza infection usually in the presence of high and persistent fever. Thermolabile carnitine palmitoyltransferase II enzyme (CPT-II) predisposes IAE, so far only described in Japanese. As the genetic origins of Japanese and Chinese are alike, similar genetic risk factors in CPT-II are expected. We report the first two unrelated Chinese patients of thermolabile CPT-II variants that underlain the persistent high fever-triggered viral infection-associated encephalopathy, multi-organ failure and death. Elevated (C16:0+C18:1)/C2 acylcarnitines ratio and the CPT2 susceptibility variant allele p.Phe352Cys; p.Val368Ile were detected. The asymptomatic family members of one patient also had abnormal long-chain acylcarnitines. In our experience of biochemical genetics, the elevated (C16:0C18:1)/C2 acylcarnitines ratio is unusual and specific for thermolabile CPT-II variants. Allele frequency of p.Phe352Cys; p.Val368Ile among Hong Kong Chinese was 0.104, similar to Japanese data, and p.Phe352Cys has not been reported in Caucasians. This may explain the Asian-specific phenomenon of thermolabile CPT-II-associated IAE. We successfully demonstrated the thermolabile CPT-II variants in patients with viral infection-associated encephalopathy in another Asian population outside Japanese. The condition is likely under-recognized. With our first cases, it is envisaged that more cases will be diagnosed in subsequent years. The exact pathogenic mechanism of how other factors interplay with thermolabile CPT-II variants and high fever leading to IAE, is yet to be elucidated. Fasting and decreased intake during illness may aggravate the disease. Further studies including high risk and neonatal screening are warranted to investigate its expressivity, penetrance and temperature-dependent behaviors in thermolabile CPT-II carriers. This may lead to discovery of the therapeutic golden window by aggressive antipyretics and L-carnitine administration in avoiding the high mortality and morbidity of IAE. © 2011 The Japan Society of Human Genetics All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/145487
ISSN
2023 Impact Factor: 2.6
2023 SCImago Journal Rankings: 1.148
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorMak, CMen_HK
dc.contributor.authorLam, CWen_HK
dc.contributor.authorFong, NCen_HK
dc.contributor.authorSiu, WKen_HK
dc.contributor.authorLee, HCHen_HK
dc.contributor.authorSiu, TSen_HK
dc.contributor.authorLai, CKen_HK
dc.contributor.authorLaw, CYen_HK
dc.contributor.authorTong, SFen_HK
dc.contributor.authorPoon, WTen_HK
dc.contributor.authorLam, DSYen_HK
dc.contributor.authorNg, HLen_HK
dc.contributor.authorYuen, YPen_HK
dc.contributor.authorTam, Sen_HK
dc.contributor.authorQue, TLen_HK
dc.contributor.authorKwong, NSen_HK
dc.contributor.authorChan, AYWen_HK
dc.date.accessioned2012-02-23T12:11:31Z-
dc.date.available2012-02-23T12:11:31Z-
dc.date.issued2011en_HK
dc.identifier.citationJournal Of Human Genetics, 2011, v. 56 n. 8, p. 617-621en_HK
dc.identifier.issn1434-5161en_HK
dc.identifier.urihttp://hdl.handle.net/10722/145487-
dc.description.abstractInfluenza-associated encephalopathy (IAE) is a potentially fatal neurological complication of influenza infection usually in the presence of high and persistent fever. Thermolabile carnitine palmitoyltransferase II enzyme (CPT-II) predisposes IAE, so far only described in Japanese. As the genetic origins of Japanese and Chinese are alike, similar genetic risk factors in CPT-II are expected. We report the first two unrelated Chinese patients of thermolabile CPT-II variants that underlain the persistent high fever-triggered viral infection-associated encephalopathy, multi-organ failure and death. Elevated (C16:0+C18:1)/C2 acylcarnitines ratio and the CPT2 susceptibility variant allele p.Phe352Cys; p.Val368Ile were detected. The asymptomatic family members of one patient also had abnormal long-chain acylcarnitines. In our experience of biochemical genetics, the elevated (C16:0C18:1)/C2 acylcarnitines ratio is unusual and specific for thermolabile CPT-II variants. Allele frequency of p.Phe352Cys; p.Val368Ile among Hong Kong Chinese was 0.104, similar to Japanese data, and p.Phe352Cys has not been reported in Caucasians. This may explain the Asian-specific phenomenon of thermolabile CPT-II-associated IAE. We successfully demonstrated the thermolabile CPT-II variants in patients with viral infection-associated encephalopathy in another Asian population outside Japanese. The condition is likely under-recognized. With our first cases, it is envisaged that more cases will be diagnosed in subsequent years. The exact pathogenic mechanism of how other factors interplay with thermolabile CPT-II variants and high fever leading to IAE, is yet to be elucidated. Fasting and decreased intake during illness may aggravate the disease. Further studies including high risk and neonatal screening are warranted to investigate its expressivity, penetrance and temperature-dependent behaviors in thermolabile CPT-II carriers. This may lead to discovery of the therapeutic golden window by aggressive antipyretics and L-carnitine administration in avoiding the high mortality and morbidity of IAE. © 2011 The Japan Society of Human Genetics All rights reserved.en_HK
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/jhg/index.htmlen_HK
dc.relation.ispartofJournal of Human Geneticsen_HK
dc.subjectChineseen_US
dc.subjectCoxsackie Virusen_US
dc.subjectH1n1 Human Swine Influenzaen_US
dc.subjectInfluenza-Associated Encephalopathyen_US
dc.subjectThermolabile Carnitine Palmitoyltransferase Iien_US
dc.subjectViral Infection-Associated Encephalopathyen_US
dc.subject.meshAmino Acid Substitutionen_HK
dc.subject.meshBase Sequenceen_HK
dc.subject.meshCarnitine - analogs & derivatives - metabolismen_HK
dc.subject.meshCarnitine O-Palmitoyltransferase - genetics - metabolismen_HK
dc.subject.meshChild, Preschoolen_HK
dc.subject.meshDNA Mutational Analysisen_HK
dc.subject.meshEncephalitis, Viral - complications - enzymology - geneticsen_HK
dc.subject.meshEnzyme Stabilityen_HK
dc.subject.meshFamily Healthen_HK
dc.subject.meshFatal Outcomeen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshGenetic Predisposition to Disease - geneticsen_HK
dc.subject.meshGenotypeen_HK
dc.subject.meshHumansen_HK
dc.subject.meshInfluenza, Human - complicationsen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMolecular Sequence Dataen_HK
dc.subject.meshMutationen_HK
dc.subject.meshPedigreeen_HK
dc.subject.meshRisk Factorsen_HK
dc.subject.meshTemperatureen_HK
dc.titleFatal viral infection-associated encephalopathy in two Chinese boys: A genetically determined risk factor of thermolabile carnitine palmitoyltransferase II variantsen_HK
dc.typeArticleen_HK
dc.identifier.emailLam, CW:ching-wanlam@pathology.hku.hken_HK
dc.identifier.emailLaw, CY:ericlaw@pathology.hku.hken_HK
dc.identifier.authorityLam, CW=rp00260en_HK
dc.identifier.authorityLaw, CY=rp01586en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1038/jhg.2011.63en_HK
dc.identifier.pmid21697855-
dc.identifier.scopuseid_2-s2.0-80052136898en_HK
dc.identifier.hkuros201649-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-80052136898&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume56en_HK
dc.identifier.issue8en_HK
dc.identifier.spage617en_HK
dc.identifier.epage621en_HK
dc.identifier.eissn1435-232X-
dc.identifier.isiWOS:000294246100014-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.issnl1434-5161-

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