Defective mitochondrial adenosine triphosphate production in skeletal muscle from patients with dominant optic atrophy due to OPA1 mutations

Raffaele Lodi, Caterina Tonon, Maria Lucia Valentino, David Manners, Claudia Testa, Emil Malucelli, Chiara La Morgia, Piero Barboni, Michele Carbonelli, Simone Schimpf, Bernd Wissinger, Massimo Zeviani, Agostino Baruzzi, Rocco Liguori, Bruno Barbiroli, Valerio Carelli

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: To assess whether impaired energy metabolism in skeletal muscle is a hallmark feature of patients with dominant optic atrophy due to several different mutations in the OPA1 gene. Design: We used phosphorus 31 magnetic resonance spectroscopy to assess calf muscle oxidative metabolism in subjects with molecularly defined dominant optic atrophy carrying different mutations in the OPA1 gene. In a subset of patients, we also evaluated serum lactate levels after exercise and muscle biopsy results for histology and mitochondrial DNA analysis. Setting: University neuromuscular and neurogenetics and magnetic resonance imaging units. Patients: Eighteen patients with dominant optic atrophy were enrolled from 8 unrelated families, 7 of which carried an OPA1 mutation predicted to induce haplo-insufficiency and 1 with a missense mutation in exon 27. Fifteen patients had documented optic atrophy. Main Outcome Measures: Presence of skeletal muscle mitochondrial oxidative phosphorylation dysfunction as assessed by phosphorus 31 magnetic resonance spectroscopy, serum lactate levels, and histological and mitochondrial DNA analysis. Results: Phosphorus 31 magnetic resonance spectroscopy showed reduced phosphorylation potential in the calf muscle at rest in patients with an OPA1 mutation (-24% from normal mean; P = .003) as well as a reduced maximum rate of mitochondrial adenosine triphosphate synthesis (-36%; P

Original languageEnglish
Pages (from-to)67-73
Number of pages7
JournalArchives of Neurology
Volume68
Issue number1
DOIs
Publication statusPublished - Jan 2011

ASJC Scopus subject areas

  • Clinical Neurology

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