Fatal human herpesvirus 6-associated encephalitis in two boys with underlying POLG mitochondrial disorders

Duha Al-Zubeidi, Mathula Thangarajh, Sheel Pathak, Chunyu Cai, Bradley L. Schlaggar, Gregory A. Storch, Dorothy K. Grange, Michael E. Watson

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background Human herpesvirus 6 is a significant cause of the febrile illness roseola infantum in young children. Infection with human herpesvirus 6 typically causes a self-limited febrile illness but occasionally is associated with central nervous system manifestations, including febrile seizures and encephalitis. Host factors associated with severe manifestations of human herpesvirus 6-associated neurological disease remain poorly characterized. Case Reports We report two previously healthy young boys with human herpesvirus 6-associated encephalitis who developed a progressive, and ultimately fatal, encephalopathy with refractory movement disorder concurrent with acquisition of acute human herpesvirus 6 infection. Both children were treated with the antiviral ganciclovir without improvement of their neurological symptoms, although quantitative human herpesvirus 6 polymerase chain reaction of cerebrospinal fluid and/or blood confirmed a decline in viral load with treatment. The clinical course in both cases was most consistent with Alpers-Huttenlocher syndrome, given the intractable seizures, developmental regression, and, ultimately, death due to liver and renal failure. In support of this, postmortem analysis identified both children to be compound heterozygous for mutations in the mitochondrial polymerase γ gene, POLG. Conclusions POLG mutations are associated with Alpers-Huttenlocher syndrome; however, no prior studies have examined the role of acute human herpesvirus 6 infection in these patients presenting with severe neurological disease. It is possible the POLG mutation phenotype was unmasked and/or exacerbated by human herpesvirus 6 infection in these two patients, potentially contributing to a more rapid clinical deterioration. This report provides new insight into a previously unrecognized association between POLG mutations and poor neurological outcome after human herpesvirus 6 infection.

Original languageEnglish (US)
Pages (from-to)448-452
Number of pages5
JournalPediatric Neurology
Volume51
Issue number3
DOIs
StatePublished - Jan 1 2014

Fingerprint

Human Herpesvirus 6
Mitochondrial Diseases
Herpesviridae Infections
Diffuse Cerebral Sclerosis of Schilder
Mutation
Exanthema Subitum
Fever
Febrile Seizures
Ganciclovir
Mitochondrial Genes
Human Herpesvirus 6 encephalitis
Liver Failure
Movement Disorders
Brain Diseases
Encephalitis
Viral Load
Renal Insufficiency
Antiviral Agents
Cerebrospinal Fluid
Seizures

Keywords

  • child
  • encephalitis
  • human herpesvirus 6 (HHV-6)
  • POLG

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Neurology
  • Developmental Neuroscience
  • Clinical Neurology

Cite this

Fatal human herpesvirus 6-associated encephalitis in two boys with underlying POLG mitochondrial disorders. / Al-Zubeidi, Duha; Thangarajh, Mathula; Pathak, Sheel; Cai, Chunyu; Schlaggar, Bradley L.; Storch, Gregory A.; Grange, Dorothy K.; Watson, Michael E.

In: Pediatric Neurology, Vol. 51, No. 3, 01.01.2014, p. 448-452.

Research output: Contribution to journalArticle

Al-Zubeidi, D, Thangarajh, M, Pathak, S, Cai, C, Schlaggar, BL, Storch, GA, Grange, DK & Watson, ME 2014, 'Fatal human herpesvirus 6-associated encephalitis in two boys with underlying POLG mitochondrial disorders', Pediatric Neurology, vol. 51, no. 3, pp. 448-452. https://doi.org/10.1016/j.pediatrneurol.2014.04.006
Al-Zubeidi, Duha ; Thangarajh, Mathula ; Pathak, Sheel ; Cai, Chunyu ; Schlaggar, Bradley L. ; Storch, Gregory A. ; Grange, Dorothy K. ; Watson, Michael E. / Fatal human herpesvirus 6-associated encephalitis in two boys with underlying POLG mitochondrial disorders. In: Pediatric Neurology. 2014 ; Vol. 51, No. 3. pp. 448-452.
@article{948d119df0a943ad8693772c3e02288c,
title = "Fatal human herpesvirus 6-associated encephalitis in two boys with underlying POLG mitochondrial disorders",
abstract = "Background Human herpesvirus 6 is a significant cause of the febrile illness roseola infantum in young children. Infection with human herpesvirus 6 typically causes a self-limited febrile illness but occasionally is associated with central nervous system manifestations, including febrile seizures and encephalitis. Host factors associated with severe manifestations of human herpesvirus 6-associated neurological disease remain poorly characterized. Case Reports We report two previously healthy young boys with human herpesvirus 6-associated encephalitis who developed a progressive, and ultimately fatal, encephalopathy with refractory movement disorder concurrent with acquisition of acute human herpesvirus 6 infection. Both children were treated with the antiviral ganciclovir without improvement of their neurological symptoms, although quantitative human herpesvirus 6 polymerase chain reaction of cerebrospinal fluid and/or blood confirmed a decline in viral load with treatment. The clinical course in both cases was most consistent with Alpers-Huttenlocher syndrome, given the intractable seizures, developmental regression, and, ultimately, death due to liver and renal failure. In support of this, postmortem analysis identified both children to be compound heterozygous for mutations in the mitochondrial polymerase γ gene, POLG. Conclusions POLG mutations are associated with Alpers-Huttenlocher syndrome; however, no prior studies have examined the role of acute human herpesvirus 6 infection in these patients presenting with severe neurological disease. It is possible the POLG mutation phenotype was unmasked and/or exacerbated by human herpesvirus 6 infection in these two patients, potentially contributing to a more rapid clinical deterioration. This report provides new insight into a previously unrecognized association between POLG mutations and poor neurological outcome after human herpesvirus 6 infection.",
keywords = "child, encephalitis, human herpesvirus 6 (HHV-6), POLG",
author = "Duha Al-Zubeidi and Mathula Thangarajh and Sheel Pathak and Chunyu Cai and Schlaggar, {Bradley L.} and Storch, {Gregory A.} and Grange, {Dorothy K.} and Watson, {Michael E.}",
year = "2014",
month = "1",
day = "1",
doi = "10.1016/j.pediatrneurol.2014.04.006",
language = "English (US)",
volume = "51",
pages = "448--452",
journal = "Pediatric Neurology",
issn = "0887-8994",
publisher = "Elsevier Inc.",
number = "3",

}

TY - JOUR

T1 - Fatal human herpesvirus 6-associated encephalitis in two boys with underlying POLG mitochondrial disorders

AU - Al-Zubeidi, Duha

AU - Thangarajh, Mathula

AU - Pathak, Sheel

AU - Cai, Chunyu

AU - Schlaggar, Bradley L.

AU - Storch, Gregory A.

AU - Grange, Dorothy K.

AU - Watson, Michael E.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Background Human herpesvirus 6 is a significant cause of the febrile illness roseola infantum in young children. Infection with human herpesvirus 6 typically causes a self-limited febrile illness but occasionally is associated with central nervous system manifestations, including febrile seizures and encephalitis. Host factors associated with severe manifestations of human herpesvirus 6-associated neurological disease remain poorly characterized. Case Reports We report two previously healthy young boys with human herpesvirus 6-associated encephalitis who developed a progressive, and ultimately fatal, encephalopathy with refractory movement disorder concurrent with acquisition of acute human herpesvirus 6 infection. Both children were treated with the antiviral ganciclovir without improvement of their neurological symptoms, although quantitative human herpesvirus 6 polymerase chain reaction of cerebrospinal fluid and/or blood confirmed a decline in viral load with treatment. The clinical course in both cases was most consistent with Alpers-Huttenlocher syndrome, given the intractable seizures, developmental regression, and, ultimately, death due to liver and renal failure. In support of this, postmortem analysis identified both children to be compound heterozygous for mutations in the mitochondrial polymerase γ gene, POLG. Conclusions POLG mutations are associated with Alpers-Huttenlocher syndrome; however, no prior studies have examined the role of acute human herpesvirus 6 infection in these patients presenting with severe neurological disease. It is possible the POLG mutation phenotype was unmasked and/or exacerbated by human herpesvirus 6 infection in these two patients, potentially contributing to a more rapid clinical deterioration. This report provides new insight into a previously unrecognized association between POLG mutations and poor neurological outcome after human herpesvirus 6 infection.

AB - Background Human herpesvirus 6 is a significant cause of the febrile illness roseola infantum in young children. Infection with human herpesvirus 6 typically causes a self-limited febrile illness but occasionally is associated with central nervous system manifestations, including febrile seizures and encephalitis. Host factors associated with severe manifestations of human herpesvirus 6-associated neurological disease remain poorly characterized. Case Reports We report two previously healthy young boys with human herpesvirus 6-associated encephalitis who developed a progressive, and ultimately fatal, encephalopathy with refractory movement disorder concurrent with acquisition of acute human herpesvirus 6 infection. Both children were treated with the antiviral ganciclovir without improvement of their neurological symptoms, although quantitative human herpesvirus 6 polymerase chain reaction of cerebrospinal fluid and/or blood confirmed a decline in viral load with treatment. The clinical course in both cases was most consistent with Alpers-Huttenlocher syndrome, given the intractable seizures, developmental regression, and, ultimately, death due to liver and renal failure. In support of this, postmortem analysis identified both children to be compound heterozygous for mutations in the mitochondrial polymerase γ gene, POLG. Conclusions POLG mutations are associated with Alpers-Huttenlocher syndrome; however, no prior studies have examined the role of acute human herpesvirus 6 infection in these patients presenting with severe neurological disease. It is possible the POLG mutation phenotype was unmasked and/or exacerbated by human herpesvirus 6 infection in these two patients, potentially contributing to a more rapid clinical deterioration. This report provides new insight into a previously unrecognized association between POLG mutations and poor neurological outcome after human herpesvirus 6 infection.

KW - child

KW - encephalitis

KW - human herpesvirus 6 (HHV-6)

KW - POLG

UR - http://www.scopus.com/inward/record.url?scp=84907347252&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84907347252&partnerID=8YFLogxK

U2 - 10.1016/j.pediatrneurol.2014.04.006

DO - 10.1016/j.pediatrneurol.2014.04.006

M3 - Article

C2 - 25160553

AN - SCOPUS:84907347252

VL - 51

SP - 448

EP - 452

JO - Pediatric Neurology

JF - Pediatric Neurology

SN - 0887-8994

IS - 3

ER -