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.
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.
Authors: Robert Reinhold; Vivien Krüger; Michael Meinecke; Christian Schulz; Bernhard Schmidt; Silke D Grunau; Bernard Guiard; Nils Wiedemann; Martin van der Laan; Richard Wagner; Peter Rehling; Jan Dudek Journal: Mol Cell Biol Date: 2012-10-08 Impact factor: 4.272
Authors: Caterina Garone; Juan Carlos Rubio; Sarah E Calvo; Ali Naini; Kurenai Tanji; Salvatore Dimauro; Vamsi K Mootha; Michio Hirano Journal: Arch Neurol Date: 2012-12
Authors: A Spinazzola; F Invernizzi; F Carrara; E Lamantea; A Donati; M Dirocco; I Giordano; M Meznaric-Petrusa; E Baruffini; I Ferrero; M Zeviani Journal: J Inherit Metab Dis Date: 2008-12-27 Impact factor: 4.982