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An In Vitro Approach to Study Mitochondrial Dysfunction: A Cybrid Model
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Hepatic presentations of mitochondrial DNA depletion syndrome in children: A single tertiary liver centre experience

R Vara1,2, M Pinon1, C Fratter3

  • 1Paediatric Liver, Gastroenterology and Nutrition Centre, King's College Hospital, London, UK.

Journal of Inherited Metabolic Disease
|May 19, 2023
PubMed

Insights

Mitochondrial DNA depletion syndromes (MDDS) present with varied liver and brain issues. Early genetic testing is crucial, especially for infantile acute liver failure, as some MPV17 gene mutation patients may benefit from liver transplantation.

Area of Science:

  • Genetics and Genomics
  • Hepatology
  • Pediatric Neurology

Background:

  • Mitochondrial DNA depletion syndromes (MDDS) encompass a diverse group of genetic disorders.
  • The hepato-cerebral phenotype associated with MDDS exhibits significant variability.
  • Understanding the specific genetic mutations and their clinical manifestations is critical for patient management.

Purpose of the Study:

  • To retrospectively analyze the clinical presentation, outcomes, and genetic basis of MDDS in pediatric patients.
  • To investigate the correlation between specific gene mutations (POLG, DGUOK, MPV17) and the hepato-cerebral phenotype.
  • To evaluate the role and outcomes of liver transplantation (LT) in MDDS patients with infantile acute liver failure.

Main Methods:

  • A single-center retrospective study of 24 pediatric patients diagnosed with MDDS between 2002 and 2019.
  • Classification of patients based on causative genes: POLG, DGUOK, and MPV17.
  • Analysis of clinical data including age at presentation, liver function tests, neurological involvement, liver histology, and survival rates.

Main Results:

  • Sixteen patients presented with acute liver failure (ALF), and eight with chronic cholestasis.
  • DGUOK and MPV17 mutations were associated with severe early-onset ALF or rapidly progressive cholestasis, often leading to death before 12 months.
  • Three MPV17 patients underwent successful liver transplantation, remaining alive years post-procedure.

Conclusions:

  • Mutations in DGUOK and MPV17 genes confer a severe phenotype in MDDS, necessitating prompt diagnosis.
  • Liver transplantation can be a viable option for a subset of MPV17 MDDS patients.
  • Rapid genetic testing is advised for infantile ALF to guide timely therapeutic decisions, including consideration for LT.

Keywords:
acute liver failurecholestasishepaticliver transplantationmitochondrial depletion syndrome

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