Relationship of primary mitochondrial respiratory chain dysfunction to fiber type abnormalities in skeletal muscle

Abstract

Variation in the size and relative proportion of type 1 and type 2 muscle fibers can occur in a number of conditions, including structural myopathies, neuropathies, and various syndromes. In most cases, the pathogenesis of such fiber type changes is unknown and the etiology is heterogeneous. Skeletal muscle mitochondrial respiratory chain analysis was performed in 10 children aged 3 weeks to 5 years with abnormalities in muscle fiber type, size, and proportion. Five children were classified as having definite, four as probable, and one as possible mitochondrial disease. Type 1 fiber predominance was the most common histological finding (six of 10). On light microscopy, four cases had subtle concomitants of a mitochondriopathy, including mildly increased glycogen, lipid, and/or succinate dehydrogenase staining, and one case had more prominent evidence of underlying mitochondrial disease with marked subsarcolemmal staining. Most cases (nine of 10) had abnormal mitochondrial morphology on electron microscopy. All were found to have mitochondrial electron transport chain (ETC) abnormalities and met diagnostic criteria for mitochondrial disease. We did not ascertain any patients who had isolated fiber type abnormalities and normal respiratory chain analysis during the period of study. We conclude that mitochondrial ETC disorders may represent an etiology of at least a subset of muscle fiber type abnormalities. To establish an etiologic diagnosis and to determine the frequency of such changes in mitochondrial disease, we suggest analysis of ETC function in individuals with fiber type changes in skeletal muscle, even in the absence of light histological features suggestive of mitochondrial disorders.

Investigation of children for mitochondriopathy confirms need for strict patient selection, improved morphological criteria, and better laboratory methods

“…Our results support the proposal that quantitative changes of type I myofibers may accompany mitochondriopathy in some cases [21,22]. However, type I myofiber abnormalities are prevalent in muscle biopsies from infants and young children with a wide diversity of underlying disorders of the central and peripheral nervous system, primary myopathies, or muscle maturation delay of uncertain etiology.…”

Pathological mechanisms underlying single large‐scale mitochondrial DNA deletions

“…Studies on the metabolic profile of muscle fibers in patients with OXPHOS deficiency are sparse and sometimes contradictory, reporting either no fiber type predominance,21 a type I predominance,15, 43, 44, 45, 46 or a type II predominance 47. Interestingly, we found higher respiratory chain deficiency in type II fibers over type I in 5 of 6 patients.…”

Relationship between work rate and oxygen uptake in mitochondrial myopathy during ramp-incremental exercise

“…These results were not due to a faster rate of work rate incrementation in patients as the ramp duration did not differ between patients and controls. Although muscle fiber typing was not performed in the present study, a selective reduction in the type II fiber population could be related to this phenomenon and/or MM patients may have an impaired ability to recruit these fibers (35,36). Alternatively, the deleterious heteroplasmic mtDNA alterations may have equally affected type I and type II fibers (12).…”