Acute liver failure due to DGUOK deficiency-is liver transplantation justified?

Irena Jankowska, Piotr Czubkowski, Dariusz Rokicki, Patryk Lipiński, Dorota Piekutowska-Abramczuk, Elżbieta Ciara, Rafał Płoski, Piotr Kaliciński, Marek Szymczak, Joanna Pawłowska, Piotr Socha

Journal: Clinics and research in hepatology and gastroenterology 2021;45(1):101408

PMID: 32278775

Full Text on Elsevier Science View on PubMed

Abstract

BACKGROUND

Deoxyguanosine kinase (DGUOK) deficiency is one of the causes of the hepatocerebral form of mitochondrial depletion syndrome (MDS). It is characterized by an early onset of liver failure with concomitant neurological deterioration. In the current literature, there are only few reports regarding long-term observation of children with DGUOK deficiency. Liver transplantation (LTx) is controversial due to extrahepatic involvement and unpredictable outcome.

METHODS

Five patients (2 boys) from 4 different families with hepatocerebral MDS associated with DGUOK mutations diagnosed with liver failure were treated in our hospital between 2010-2019.

RESULTS

In all children clinical symptoms developed within the first days of live and hypoglycemia (hypoketotic), conjugated hyperbilirubinemia (cholestasis), severe lactic acidosis, and coagulopathy were observed. Two neonates had low birth-weight for gestational age and failed to thrive. Mild neurological involvement as hypotonia was observed in all children. Three children died at the age of 2, 6 months and 6,5 months of age, respectively, due to end-stage liver failure. In one case, LTx was not considered, in two patients (sisters) parents did not agree to this procedure. LTx was subsequently performed in two patients at the age of 6 and 7 months, respectively, one from deceased, and one from living related donor, in both before the final confirmation of DGUOK mutations. One boy died 2 months after LTx due to post-LTx procedure-related complications; one is still alive with 3years of follow-up, with good liver function and mild neurological disturbances. The diagnosis of DGUOK deficiency was confirmed by biallelic DGUOK mutations detection. Equally, patients were compound heterozygotes (three cases) and homozygotes (two cases). Three known molecular variants, including regulatory substitutions (c.1A>G, c.3G>A) and in-frame insertion (c.813_814insTTT) were identified.

CONCLUSIONS

Prognosis in patients with DGUOK deficiency is generally poor. Based on a review of the literature and our experience liver transplantation in selected patients with DGUOK mutation does not appear to be contraindicated, especially in those without or with minimal neurologic abnormalities.

Address: Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics, Children's Memorial Health Institute, Al. Dzieci Polskich 20, Warsaw, Poland. Electronic address: [email protected].; Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics, Children's Memorial Health Institute, Al. Dzieci Polskich 20, Warsaw, Poland.; Department of Pediatrics, Nutrition and Metabolic Diseases, The Children's Memorial Health Institute, Warsaw, Poland.; Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland.; Department of Medical Genetics, Medical University of Warsaw, Warsaw, Poland.; Department of Pediatric Surgery and Organ Transplantation, The Children's Memorial Health Institute, Warsaw, Poland.

DOI: 10.1016/j.clinre.2020.02.018