Progressive cytochrome c oxidase deficiency in a case of earns‐sayre syndrome: Morphological, immunological, and biochemical studies in muscle biopsies and autopsy tissues

Abstract

We report biochemical, immunological, and morphological findings in a patient with fatal Kearns-Sayre syndrome. Histochemical and biochemical findings from muscle biopsy specimens obtained 7 years apart documented the disease's evolution from a mild mitochondrial disorder affecting a small proportion of muscle fibers to a severe disorder affecting a large proportion of muscle fibers. Cytochrome c oxidase activity in muscle declined profoundly as the disease progressed, although the level of enzyme protein was normal, as shown by immunochemical techniques. Other organs were severely affected by the disease. Examination of postmortem tissue showed spongiosis in the frontal cortex, diffuse loss of Purkinje cells in the cerebellum, liver steatosis, and heart fibrosis with mitochondrial abnormalities. Cytochrome c oxidase activity was only slightly reduced in these organs.

Renal manifestations of primary mitochondrial disorders

“…A further differentiation of renal involvement in MIDs relies on whether the underlying genotype manifests clinically or remains subclinical. Subclinical involvement may be detected upon observation of morphological abnormalities of mitochondria and a high quantity of heteroplasmy of mutated mtDNA during kidney biopsy or autopsy (11,12).…”

Extensive Defects of Mitochondrial Electron-Transfer Chain in Muscular Cytochrome c Oxidase Deficiency

“…5B, arrowhead). Numbers in lanes 7,8, and 9 represent the subunit numbers of complexes 111, IV, and V, respectively. The mol.…”

“…In addition, focal deficiency of complex IV, mainly observed in Kearns-Sayre syndrome (8) or in chronic progressive external ophthalmoplegia (CPEO) (9), is also recognized. However, the molecular basis for the heterogeneity in the clinical features of complex IV deficiency is not fully elucidated.…”

Plasticity of Skeletal Muscle Mitochondria in Response to Contractile Activity

“…These histological changes are similar to the 'ragged red fibres' typically observed in mitochondrial myopathy patients (Muller-Hocker, 1990;Rifai et al 1995), which result from an abnormal proliferation of subsarcolemmal mitochondria. This represents the most common morphological change associated with impaired oxidative phosphorylation (Bresolin et al 1987;Bua et al 2002) as a result of mtDNA defects. While it is known that endurance training can ameliorate the decline in enzyme activities evident in older individuals (Young et al 1983), the role of exercise-induced mitochondrial biogenesis in other agerelated mitochondrial processes, as noted above, is currently unknown.…”