title: Hepatocerebral mitochondrial DNA depletion syndrome caused by deoxyguanosine kinase (DGUOK) mutations.
abstract: BACKGROUND
  Autosomal recessive mutations in deoxyguanosine kinase (DGUOK) have been identified in the hepatocerebral form of mitochondrial DNA (mtDNA) depletion syndrome.
  
  
  OBJECTIVE
  To describe the clinical spectrum of DGUOK-related mtDNA depletion syndrome in 6 children and to summarize the literature.
  
  
  RESULTS
  We identified pathogenic mutations in DGUOK in 6 children with the hepatocerebral form of mtDNA depletion syndrome. We describe the clinical, neuroradiologic, histologic, and genetic features in these children. All children showed severe hepatopathy, while involvement of other organs (skeletal muscle and brain) was variable. We identified 5 novel mutations (1 of them in 2 children) and 2 previously described mutations. Three different mutations affected the initial methionine, suggesting a mutational hot spot. One of our patients underwent liver transplantation; pathologic findings revealed (in addition to diffuse hepatopathy) a hepatocellular carcinoma, implying a possible link between mtDNA depletion syndrome and tumorigenesis.
  
  
  CONCLUSIONS
  We studied 12 children with infantile hepatoencephalopathies and mtDNA depletion syndrome and found pathogenic DGUOK mutations in 6, suggesting that this gene defect is a frequent but not an exclusive cause of the hepatic form of mtDNA depletion syndrome.
authors.affiliation: Institute of Clinical Chemistry, Metabolic Disease Center Munich-Schwabing, Kölner Platz 1, 80804 Munich, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Freisinger
authors.forename: Nancy
authors.initials: N
authors.lastname: Fütterer
authors.forename: Erwin
authors.initials: E
authors.lastname: Lankes
authors.forename: Klaus
authors.initials: K
authors.lastname: Gempel
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Berger
authors.forename: Johannes
authors.initials: J
authors.lastname: Spalinger
authors.forename: Alexandra
authors.initials: A
authors.lastname: Hoerbe
authors.forename: Claudia
authors.initials: C
authors.lastname: Schwantes
authors.forename: Martin
authors.initials: M
authors.lastname: Lindner
authors.forename: René
authors.initials: R
authors.lastname: Santer
authors.forename: Martin
authors.initials: M
authors.lastname: Burdelski
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Schaefer
authors.forename: Bernhard
authors.initials: B
authors.lastname: Setzer
authors.forename: Ulrich A
authors.initials: UA
authors.lastname: Walker
authors.forename: Rita
authors.initials: R
authors.lastname: Horváth
mesh_terms: D002675:Child, Preschool; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006501:Hepatic Encephalopathy / Q000201:enzymology* / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D028361:Mitochondrial Diseases / Q000201:enzymology / Q000235:genetics; D020125:Mutation, Missense / Q000235:genetics*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics* / Q000378:metabolism; D013577:Syndrome
chemical_list: D004272:DNA, Mitochondrial; D017853:Phosphotransferases (Alcohol Group Acceptor); C019165:deoxyguanosine kinase