Mitochondrial Diseases and Myopathies: A Series of Muscle Biopsy Specimens with Ultrastructural Changes in the Mitochondria

Abstract

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.

Endurance exercise rescues progeroid aging and induces systemic mitochondrial rejuvenation in mtDNA mutator mice

“…4G). Similar alterations in mitochondrial morphology have been documented to occur with age and in humans with mitochondrial myopathy (47,48). Endurance exercise abrogated these morphological irregularities in mitochondrial morphology in PolG-END mice (Fig.…”

Presentation and Diagnosis of Mitochondrial Disorders in Children

“…Ultrastructural findings include an increase in mitochondrial number (48%) or size (7%), increased lipid (8%), glycogen droplets (12%), increased mitochondrial matrix, abnormal cristae, and paracrystalline inclusions (3%) [15,38,44]. Similar ultrastructural changes to the mitochondria can be seen in a variety of other conditions, including muscular dystrophies, neurogenic atrophy, inflammatory myopathies, antiretroviral therapy treatment, chronic steroid use, aging, or other metabolic disorders [14,43]. As with normal light microscopy, normal electron microscopy does not eliminate the possibility of a mitochondrial disorder.…”

“…As with other findings in mitochondrial patients, light microscopy changes are generally nonspecific, and although commonly associated with mitochondrial disorders, ragged-red fibers may be evident in normal aging, antiretroviral therapy, muscular dystrophies, myositis, and inflammatory myopathies [31]. Other findings in the muscle biopsies of patients with mitochondrial disorders include internal nuclei, atrophic fibers, increased lipid droplets, fiber-type grouping, type I or type II fiber atrophy, fiber hypertrophy, glycogen, and inflammation [14,31,41,43]. In summary, the histologic evaluation of muscle may provide evidence to support a diagnosis of a mitochondrial disorder, but muscle pathology is more common with mitochondrial DNA mutations and with advancing age.…”

Homozygosity mapping of Marinesco–Sjögren syndrome to 5q31

“…Myopathic changes including subsarcolemmal accumulation of abnormal mitochondria of various shapes and sizes were described in all of them except one. 8,15,43,44 The parents of families 3 and 4 are not consanguineous and are related neither to each other, nor to family 2. The three Norwegian families originate from separate Northern Norway counties; however, both parents of family 4 originate from the same small island west of the Norwegian coast.…”