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In vivo skeletal muscle mitochondrial function in Leber's hereditary optic neuropathy assessed by 31 P magnetic resonance spectroscopy
Author(s) -
Lodi R.,
Taylor D. J.,
Tabrizi S. J.,
Kumar S.,
Sweeney M.,
Wood N. W.,
Styles P.,
Radda G. K.,
Schapira A. H. V.
Publication year - 1997
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410420407
Subject(s) - mitochondrial dna , mutation , in vivo , mitochondrion , skeletal muscle , optic neuropathy , leber's hereditary optic neuropathy , medicine , biology , endocrinology , chemistry , microbiology and biotechnology , genetics , anatomy , gene , optic nerve
Abstract We used 31 P magnetic resonance spectroscopy ( 31 P‐MRS) to asses in vivo skeletal muscle mitochondrial function in 10 Leber's hereditary optic neuropathy patients/carriers with a mitochondrial DNA (mtDNA) mutation at one of three nucleotide positions, 11,778, 14,484, and 3,460. We studied one affected patient for each mutation and two unaffected carriers with the 11,778 or 3,460 mutation and three carriers with 14,484. All subjects were homoplasmic except the two 3,460 carriers, who showed 80% and 15% of mutated mtDNA. 31 P‐MRS at rest disclosed some abnormalities in all subjects. In particular, the phosphorylation potential was below the normal range in all cases. During recovery from exercise, the maximum rate of mitochondrial ATP production ( V max ) was reduced to 27% of normal in the 11,778 mutation and to 53% in the 14,484 mutation patient/carrier groups. Mitochondrial V max was within the normal range in all subjects with the 3,460 mutation but correlated inversely with the percentage of mutated mtDNA. This in vivo study shows that the 11,778 mutation causes a mitochondrial impairment more severe than the 14,484 and that the 3,460 mutation results in only a mild depression of muscle mitochondrial function.