Hepatocerebral form of mitochondrial DNA depletion syndrome: novel MPV17 mutations

Arch Neurol. 2008 Aug;65(8):1108-13. doi: 10.1001/archneur.65.8.1108.


Background: Autosomal recessive mutations in MPV17 (OMIM *137960) have been identified in the hepatocerebral form of mitochondrial DNA depletion syndrome (MDS).

Objective: To describe the clinical, morphologic, and genetic findings in 3 children with MPV17-related MDS from 2 unrelated families.

Design: Case report.

Setting: Academic research.

Main outcome measures: We identified 3 novel pathogenic mutations in 3 children.

Results: Two children were homozygous for nonsense mutation p.W120X. A third child was compound heterozygous for missense mutation p.G24W and for a macrodeletion spanning MPV17 exon 8. All patients demonstrated lactic acidosis, hypoglycemia, hepatomegaly, and progressive liver failure. Neurologic symptoms manifested at a later stage of the disease. Death occurred within the first year of life in all 3 patients.

Conclusions: These data confirm that MPV17 mutations are associated with a 2-stage syndrome. The first symptoms are metabolic and rapidly progress to hepatic failure. This stage is followed by neurologic involvement affecting the central and peripheral systems.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Diseases, Metabolic / genetics*
  • Brain Diseases, Metabolic / metabolism
  • Brain Diseases, Metabolic / pathology
  • Codon, Nonsense / genetics*
  • DNA, Mitochondrial / genetics*
  • Fatal Outcome
  • Female
  • Genes, Recessive
  • Genome, Mitochondrial / genetics
  • Humans
  • Infant
  • Liver Failure / genetics*
  • Liver Failure / metabolism
  • Liver Failure / pathology
  • Membrane Proteins / deficiency*
  • Membrane Proteins / genetics*
  • Metabolism, Inborn Errors / genetics
  • Mitochondrial Diseases / genetics
  • Mitochondrial Diseases / metabolism
  • Mitochondrial Diseases / pathology
  • Mitochondrial Proteins / deficiency*
  • Mitochondrial Proteins / genetics*
  • Mutation, Missense / genetics*
  • Syndrome


  • Codon, Nonsense
  • DNA, Mitochondrial
  • MPV17 protein, human
  • Membrane Proteins
  • Mitochondrial Proteins

Associated data

  • OMIM/137960
  • OMIM/174763
  • OMIM/188250
  • OMIM/601465
  • OMIM/603921
  • OMIM/604712
  • OMIM/60675
  • OMIM/611224