Focal deficiency of cytochrome-c-oxidase in skeletal muscle of patients with progressive external ophthalmoplegia. Cytochemical-fine-structural study.

In skeletal muscle biopsies of 8 patients with progressive external ophthalmoplegia combined light and fine structural cytochemical studies of cytochrome-c-oxidase revealed the absence of the enzyme in single fibres with or without accumulation of abnormal mitochondria. However, some fibres showed abnormal mitochondria without any deficiency of the enzyme. In one case with only slight mitochondrial proliferation the existence of the enzyme defect was the most remarkable finding. The occurrence of the enzyme defect obviously does not depend on concomitant structural alterations of the chondriom. The results are consistent with an acquired mitochondrial injury leading to a gradual loss of enzyme activity either earlier (with or without a minimal reactive mitochondrial proliferation) or later (after a phase of mitochondrial proliferation) in the course of the disease. Focal lack of cytochrome-c-oxidase activity is apparently a constant feature of the syndrome; it therefore may be not only of pathogenetic but also of diagnostic importance and in this connection cytochemical-fine-structural demonstration of cytochrome-c-oxidase is a valuable method. In contrast to the biochemical approach it allows not only the detection but also the exact anatomical localization of single fibre defects.