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.
  
  
  METHODS
  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.
authors.affiliation: Division of Pediatric Infectious Diseases, Department of Pediatrics, Children's Mercy Hospital, Kansas City, Missouri.
authors.forename: Duha
authors.initials: D
authors.lastname: Al-Zubeidi
authors.affiliation: Division of Epilepsy, Neurophysiology, and Critical Care Neurology, Department of Neurology, Children's National Medical Center, Washington, DC.
authors.forename: Mathula
authors.initials: M
authors.lastname: Thangarajh
authors.affiliation: Department of Neurology, Washington University, St. Louis, Missouri.
authors.forename: Sheel
authors.initials: S
authors.lastname: Pathak
authors.affiliation: Department of Pathology and Immunology, Washington University, St. Louis, Missouri.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Cai
authors.affiliation: Department of Neurology, Washington University, St. Louis, Missouri.
authors.forename: Bradley L
authors.initials: BL
authors.lastname: Schlaggar
authors.affiliation: Division of Pediatric Infectious Diseases, Department of Pediatrics, Washington University, St. Louis, Missouri.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Storch
authors.affiliation: Division of Genetics and Genomic Medicine, Department of Pediatrics, Washington University, St. Louis, Missouri.
authors.forename: Dorothy K
authors.initials: DK
authors.lastname: Grange
authors.affiliation: Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Michigan, Ann Arbor, Michigan. Electronic address: mikeannaw@gmail.com.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Watson
mesh_terms: D001921:Brain / Q000473:pathology; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D018792:Encephalitis, Viral / Q000150:complications* / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D017809:Fatal Outcome; D015654:Herpesvirus 6, Human; D006801:Humans; D007223:Infant; D008297:Male; D028361:Mitochondrial Diseases / Q000150:complications* / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D009069:Movement Disorders / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D019349:Roseolovirus Infections / Q000150:complications* / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology
chemical_list: D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human
keywords: POLG; child; encephalitis; human herpesvirus 6 (HHV-6)