Clinical heterogeneity associated with mitochondrial DNA depletion in muscle

We studied 10 patients with a variable degree of mtDNA depletion in muscle. Seven patients skewed a clear-cut myopathic pattern, while the three remai ning had brain involvement. There was no relationship between age at onset and relative mtDNA copy number in muscle, but we found an apparent correlat ion between clinical severity and degree of muscle mtDNA depiction. Muscle morphology showed that mtDNA depletion was associated with mitochondrial pr oliferation and cytochrome c oxidase negative fibers. Biochemical studies r evealed single or combined defects of mtDNA-dependent respiratory chain com plexes. Our data indicate that patients with mtDNA depletion may have a mor e variable age at onset and clinical evolution and wider phenotype than pre viously thought. The diagnosis of this condition, so far regarded as rare, may have been overlooked to some extent. (C) 1998 Elsevier Science B.V. All rights reserved.