CHRONIC PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA - A CORRELATIVE STUDY OFQUANTITATIVE MOLECULAR-DATA AND HISTOCHEMICAL AND BIOCHEMICAL PROFILE

We studied muscle biopsies of 5 patients with Kearns-Sayre syndrome an d 3 patients with chronic progressive external ophthalmoplegia all wit h the common deletion. Steady state levels of normal and deleted mitoc hondrial DNA (mtDNA) measured in each patient by quantitative PCR were correlated with histochemical and biochemical features. We found that (1) normal mtDNA levels were higher in many patients than in controls ; (2) as levels of deleted mtDNA increased, so did levels of normal mt DNA; (3) cytochrome c oxidase (COX) activity and the percentage of COX negative fibers were both related to the levels of deleted mtDNA; and (4) as percentage of ragged red fibers increased, so did levels of to tal, deleted and normal mtDNA. The quantity of deleted mtDNA plays a k ey role in determining the severity of COX deficiency, which is respon sible for the overaccumulation of mitochondria in muscle.