Mitochondrial diseases and myopathies: a series of muscle biopsy specimens with ultrastructural changes in the mitochondria.

From 1986 to 1991, 472 muscle biopsy specimens from patients from different hospitals in Norway were examined. Of these, 364 were embedded for electron microscopy, and 194 were examined with electron microscopy. Ultrastructural alterations in the mitochondria were detected in 49 of these specimens. Characteristic electron microscopic findings included subsarcolemmal accumulation of abnormal mitochondria of various shapes and sizes, often containing electron-dense granules and sometimes lipid vacuoles in the mitochondria and diffusely electron-lucent matrix space. Paracrystalline inclusion bodies were seldom seen in specimens from young patients, but in some cases mitochondrial electron-dense granules at the cristae were found. These amorphous densities are consistent with lipoproteins, suggesting that they may represent an early stage of paracrystalline inclusions. Biochemical and genetic exploration of the patients with biopsy specimens suggesting mitochondrial disease indicated maternally genetic inheritance and an enzyme defect in the respiratory chain in 21 patients in two families. Three patients had MELAS syndrome, 7 Marinesco-Sjögren syndrome, and 2 Kearns-Sayre syndrome. Five family members had ptosis, cardiomyopathy, mild myopathy, and increased lactate in cerebrospinal fluid and serum. In addition to the diseases mentioned above, changes in the mitochondria were detected in other conditions such as Rett's syndrome (n = 1), ornithine transcarbamylase deficiency (n = 2), and hypothyroidism (n = 2) as well as in 3 patients with clinical and laboratory results indicative of inflammatory myopathy and 3 patients with clinical and laboratory findings consistent with peripheral neuropathy. It is concluded that, although ultrastructural changes in the mitochondria may represent unspecific findings, electron microscopic examination of muscle biopsy specimens is a useful screening method to select specimens for further biochemical analysis and to obtain an early and more precise diagnosis of the disease.