IN-VIVO SKELETAL-MUSCLE MITOCHONDRIAL-FUNCTION IN LEBERS HEREDITARY OPTIC NEUROPATHY ASSESSED BY P-31 MAGNETIC-RESONANCE SPECTROSCOPY

We used P-31 magnetic resonance spectroscopy (P-31-MRS) to assess in v ivo skeletal muscle mitochondrial function in 10 Leber's hereditary op tic neuropathy patients/carriers with a mitochondrial DNA (mtDNA) muta tion at one of three nucleotide positions, 11,778, 14,484, and 3,460. We studied one affected patient for each mutation and two unaffected c arriers with the 11,778 or 3,460 mutation and three carriers with 14,4 84. All subjects were homoplasmic except the two 3,460 carriers, who s howed 80% and 15% of mutated mtDNA. P-31-MRS at rest disclosed some ab normalities in all subjects. In particular, the phosphorylation potent ial was below the normal range in all cases. During recovery from exer cise, the maximum rate of mitochondrial ATP production (V-max) was red uced 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 no rmal range in all subjects with the 3,460 mutation but correlated inve rsely with the percentage of mutated mtDNA. This in vivo study shows t hat 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 dep ression of muscle mitochondrial function.