Abnormal neurological features predict poor survival and should preclude liver transplantation in patients with deoxyguanosine kinase deficiency

Liver Transpl. 2008 Oct;14(10):1480-5. doi: 10.1002/lt.21556.

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.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Child, Preschool
  • Contraindications
  • DNA, Mitochondrial / metabolism*
  • Female
  • Hepatic Encephalopathy / metabolism
  • Hepatic Encephalopathy / mortality
  • Hepatic Encephalopathy / surgery*
  • Humans
  • Infant
  • Kaplan-Meier Estimate
  • Liver Transplantation*
  • Male
  • Phosphotransferases (Alcohol Group Acceptor) / deficiency*
  • Prognosis

Substances

  • DNA, Mitochondrial
  • Phosphotransferases (Alcohol Group Acceptor)
  • deoxyguanosine kinase