Hepatocerebral form of mitochondrial DNA depletion syndrome: novel MPV17 mutations.

TitleHepatocerebral form of mitochondrial DNA depletion syndrome: novel MPV17 mutations.
Publication TypeJournal Article
Year of Publication2008
AuthorsSpinazzola, A, Santer, R, Akman, OH, Tsiakas, K, Schaefer, H, Ding, X, Karadimas, CL, Shanske, S, Ganesh, J, Di Mauro, S, Zeviani, M
JournalArch Neurol
Date Published2008 Aug
KeywordsBrain Diseases, Metabolic, Codon, Nonsense, DNA, Mitochondrial, Fatal Outcome, Female, Genes, Recessive, Genome, Mitochondrial, Humans, Infant, Liver Failure, Membrane Proteins, Metabolism, Inborn Errors, Mitochondrial Diseases, Mitochondrial Proteins, Mutation, Missense, Syndrome

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.

Alternate JournalArch. Neurol.
Citation Key10.1001/archneur.65.8.1108
PubMed ID18695062
Grant ListGGP07019 / / Telethon / Italy