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

• Published in: Clinical genetics 2005-10, Vol.68 (4), p.337-348
• Main Authors: Enns, GM, Hoppel, CL, DeArmond, SJ, Schelley, S, Bass, N, Weisiger, K, Horoupian, D, Packman, S
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; calcium homeostasis; Child, Preschool; congenital fiber type disproportion; Errors of metabolism; General aspects. Genetic counseling; Humans; Infant; Infant, Newborn; Medical genetics; Medical sciences; Metabolic diseases; Miscellaneous hereditary metabolic disorders; Mitochondria, Muscle - physiology; mitochondrial disease; Mitochondrial Diseases - physiopathology; Mitochondrial Myopathies - pathology; Mitochondrial Myopathies - physiopathology; muscle fiber atrophy; Muscle Fibers, Skeletal - pathology; Muscle, Skeletal - pathology; type 1 fiber predominance
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/j.1399-0004.2005.00499.x

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.