Partial cytochrome oxidase (aa3) deficiency in chronic progressive external ophthalmoplegia. Histochemical and...

Biochemical and histochemical studies were carried out on 2 patients with chronic progressive external ophthalmoplegia (CPEO). Histological examination revealed prominent ragged-red fibres in the Gomori trichrome stain and cytochrome oxidase staining revealed partial depletion of cytochrome oxidase with negative staining in some fibres with prominent subsarcolemmal mitochondrial aggregations. Polarographic studies with isolated intact skeletal muscle mitochondria revealed low State III respiration rates with NAD- and FAD-linked substrates. Cytochrome aa3 levels were depressed in the one case where a cytochrome difference spectra was recorded. Cytochrome oxidase levels were greatly depressed in muscle homogenate, whereas monoamine oxidase levels were in the normal range, indicating a selective depletion of the former enzyme complex. It is possible that deficiency of cytochrome oxidase may arise as an epiphenomenon in degenerating mitochondria rather than a primary deficiency.