title: Abnormal neurological features predict poor survival and should preclude liver transplantation in patients with deoxyguanosine kinase deficiency.
abstract: Deoxyguanosine kinase (DGUOK) deficiency is the commonest type of mitochondrial DNA depletion associated with a hepatocerebral phenotype. In this article, we evaluate predictors of survival and therapeutic options in patients with DGUOK deficiency. A systematic search of MEDLINE, LILAC, and SCIELO was carried out to identify peer-reviewed clinical trials, randomized controlled trials, meta-analyses, and other studies with clinical pertinence. DGUOK deficiency was searched with the terms dGK, DGUOK, mitochondrial DNA depletion, mtDNA, and hepatocerebral. Bibliographies of identified articles were reviewed for additional references. Thirteen identified studies met the inclusion criteria and were used in this study. The analysis revealed that DGUOK deficiency is associated with a variable clinical phenotype. Long-term survival is best predicted by the absence of profound hypotonia, significant psychomotor retardation, or nystagmus. In the presence of these features, there is increased mortality, and liver transplantation does not confer increased survival. In summary, liver transplantation appears to be futile in the presence of specific neurological signs or symptoms in patients affected with DGUOK deficiency. Conversely, in the absence of these neurological features, liver transplantation may be considered a potential treatment.
authors.affiliation: Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: David P
authors.initials: DP
authors.lastname: Dimmock
authors.forename: J Kay
authors.initials: JK
authors.lastname: Dunn
authors.forename: Annette
authors.initials: A
authors.lastname: Feigenbaum
authors.forename: Anthony
authors.initials: A
authors.lastname: Rupar
authors.forename: Rita
authors.initials: R
authors.lastname: Horvath
authors.forename: Peter
authors.initials: P
authors.lastname: Freisinger
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Mousson de Camaret
authors.forename: Lee-Jun
authors.initials: LJ
authors.lastname: Wong
authors.forename: Fernando
authors.initials: F
authors.lastname: Scaglia
mesh_terms: D002648:Child; D002675:Child, Preschool; D000075202:Contraindications; D004272:DNA, Mitochondrial / Q000378:metabolism*; D005260:Female; D006501:Hepatic Encephalopathy / Q000378:metabolism / Q000401:mortality / Q000601:surgery*; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D016031:Liver Transplantation; D008297:Male; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000172:deficiency*; D011379:Prognosis
chemical_list: D004272:DNA, Mitochondrial; D017853:Phosphotransferases (Alcohol Group Acceptor); C019165:deoxyguanosine kinase