Fatal mitochondrial cardiomyopathy in Kearns-Sayre syndrome with deficiency of cytochrome-c-oxidase in cardiac and skeletal muscle. An enzymehistochemical--ultra-immunocytochemical--fine structural study in longterm frozen autopsy tissue.

Morphological studies in a 26-year-old man with long-standing Kearns-Sayre syndrome, with cardiac arrhythmias and a fatal congestive cardiomyopathy, revealed a mitochondrial myopathy of both skeletal and myocardial muscle (Hübner et al. 1986). Histochemical investigation of cytochrome-c-oxidase showed multiple enzyme defects of both cardiac and skeletal muscle present in myocytes with normal and abnormal numbers of mitochondria demonstrated by ultracytochemistry. Immunohistochemical studies with antibodies against the holoenzyme and various subunits revealed that in the heart the enzyme defect affected both contractile and conductive fibres and was characterized by a severe reduction but not a complete loss of nuclear and mitochondrially coded immunoreactive enzyme protein. In skeletal muscle, however, where up to 30% of the fibres lacked enzyme activity, immunoreactivity was reduced only very occasionally. These results are most consistent with a defective enzyme assembly in the inner mitochondrial membrane and probably indicate heterogeneity of mitochondria, i.e. organ-specific pathological reaction patterns.