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

@article{Dimmock2008AbnormalNF,
  title={Abnormal neurological features predict poor survival and should preclude liver transplantation in patients with deoxyguanosine kinase deficiency},
  author={David P Dimmock and John K. Dunn and Annette Feigenbaum and Anthony Rupar and Rita Horvath and Peter Freisinger and B{\'e}n{\'e}dicte Mousson de Camaret and Lee-Jun C. Wong and Fernando Scaglia},
  journal={Liver Transplantation},
  year={2008},
  volume={14}
}
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… 
Long‐term outcomes after liver transplantation for deoxyguanosine kinase deficiency: A single‐center experience and a review of the literature
  • E. Grabhorn, K. Tsiakas, +6 authors R. Santer
  • Medicine
    Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
  • 2014
TLDR
Although survival after LT for DGUOK deficiency is lower than survival afterLT for other indications, a significant proportion of patients benefit from LT with long‐term survival and a stable neurological situation despite initial neurological abnormalities.
Neonatal liver failure due to deoxyguanosine kinase deficiency
Deoxyguanosine kinase (dGK) deficiency, a rare severe cause of mitochondrial DNA (mtDNA) depletion, has two forms of presentation: hepatocerebral syndrome and isolated hepatic disease. The authors
Deoxyguanosine kinase deficiency: a report of four patients
TLDR
E elevated serum tyrosine levels may alert the physicians to a DGUOK deficiency in a baby with hepatopathy in the presence of the mentioned signs, and early diagnosis is important not only for genetic counseling but also for a possible liver transplantation.
Acute liver failure due to DGUOK deficiency-is liver transplantation justified?
TLDR
Based on a review of the literature and the experience liver transplantation in selected patients with DGUOK mutation does not appear to be contraindicated, especially in those without or with minimal neurologic abnormalities.
Pediatric liver transplantation from a living donor in mitochondrial disease: Good outcomes in DGUOK deficiency?
TLDR
This case supports that even in the presence of neurological MRI findings, but in the absence of significant neurological symptoms, LT represents a viable option in DGUOK‐deficient patients who have the E227K/R118H mutation combination along with liver failure.
Deoxyguanosine Kinase Deficiency
TLDR
Care is best provided by a multidisciplinary team and Carrier testing for at-risk relatives, prenatal testing for pregnancies at increased risk, and preimplantation genetic diagnosis are possible if the DGUOK pathogenic variants in the family are known.
The first founder DGUOK mutation associated with hepatocerebral mitochondrial DNA depletion syndrome.
TLDR
A new DGUOK splice site mutation is reported that provide insight into a critical protein domain (dGK kinase domain) and the first founder mutation in a North-African population.
Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension
TLDR
The findings provide new insight into the mechanisms mediating inherited and acquired noncirrhotic portal hypertension, expand the phenotypic spectrum of DGUOK deficiency, and provide a new genetic test for a specific cause of idiopathic nonc Cirrhosis-like portal hypertension.
Post mortem identification of deoxyguanosine kinase (DGUOK) gene mutations combined with impaired glucose homeostasis and iron overload features in four infants with severe progressive liver failure
TLDR
Analysis of the natural history of the disease in patients and the literature data led to the following observations: (i) islet cell hyperplasia (and hyperinsulinism) may contribute to MDS-associated hypoglycemia; (ii) iron overload may additionally damage mtDNA-depleted tissues; (iii) low birth weight, adaptation trouble, and abnormal amino acids in newborn screening are frequent in dGK-deficient neonates.
Two patients with hepatic mtDNA depletion syndromes and marked elevations of S-adenosylmethionine and methionine.
TLDR
Evidence is presented that liver abnormalities in two patients proven by a variety of studies to have mitochondrial depletion syndromes due to mutations in either their MPV17 or DGUOK genes are very unlikely to explain their elevations of AdoMet or the extent of their hypermethioninemias.
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TLDR
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