TY - JOUR
T1 - Defective mitochondrial adenosine triphosphate production in skeletal muscle from patients with dominant optic atrophy due to OPA1 mutations
AU - Lodi, Raffaele
AU - Tonon, Caterina
AU - Valentino, Maria Lucia
AU - Manners, David
AU - Testa, Claudia
AU - Malucelli, Emil
AU - La Morgia, Chiara
AU - Barboni, Piero
AU - Carbonelli, Michele
AU - Schimpf, Simone
AU - Wissinger, Bernd
AU - Zeviani, Massimo
AU - Baruzzi, Agostino
AU - Liguori, Rocco
AU - Barbiroli, Bruno
AU - Carelli, Valerio
PY - 2011/1
Y1 - 2011/1
N2 - 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
AB - 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
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U2 - 10.1001/archneurol.2010.228
DO - 10.1001/archneurol.2010.228
M3 - Article
C2 - 20837821
AN - SCOPUS:78651304811
VL - 68
SP - 67
EP - 73
JO - Archives of Neurology
JF - Archives of Neurology
SN - 0003-9942
IS - 1
ER -