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.