Pathology of mitochondrial encephalomyopathies.
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TLDR
Muscle biopsy provides the best tissue to confirm a mitochondrial cytopathy, and quantitative determinations of respiratory chain enzyme complexes, with citrate synthase as an internal control, confirm the histochemical impressions or may be the only evidence of mitochondrial disease.Abstract:
Muscle biopsy provides the best tissue to confirm a mitochondrial cytopathy. Histochemical features often correlate with specific syndromes and facilitate the selection of biochemical and genetic studies. Ragged-red fibres nearly always indicate a combination defect of respiratory complexes I and IV. Increased punctate lipid within myofibers is a regular feature of Kearns-Sayre and PEO, but not of MELAS and MERRF. Total deficiency of succinate dehydrogenase indicates a severe defect in Complex II; total absence of cytochrome-c-oxidase activity in all myofibres correlates with a severe deficiency of Complex IV or of coenzyme-Q10. The selective loss of cytochrome-c-oxidase activity in scattered myofibers, particularly if accompanied by strong succinate dehydrogenase staining in these same fibres, is good evidence of mitochondrial cytopathy and often of a significant mtDNA mutation, though not specific for Complex IV disorders. Glycogen may be excessive in ragged-red zones. Ultrastructure provides morphological evidence of mitochondrial cytopathy, in axons and endothelial cells as well as myocytes. Abnormal axonal mitochondria may contribute to neurogenic atrophy of muscle, a secondary chronic feature. Quantitative determinations of respiratory chain enzyme complexes, with citrate synthase as an internal control, confirm the histochemical impressions or may be the only evidence of mitochondrial disease. Biological and technical artifacts may yield falsely low enzymatic activities. Genetic studies screen common point mutations in mtDNA. The brain exhibits characteristic histopathological alterations in mitochondrial diseases. Skin biopsy is useful for mitochondrial ultrastructure in smooth erector pili muscles and axons; skin fibroblasts may be grown in culture. Mitochondrial alterations occur in many nonmitochondrial diseases and also may be induced by drugs and toxins.read more
Citations
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Tissue-specific mtDNA abundance from exome data and its correlation with mitochondrial transcription, mass and respiratory activity.
Anna Maria D'Erchia,Anna Atlante,Gemma Gadaleta,Giulio Pavesi,Matteo Chiara,Caterina De Virgilio,Caterina Manzari,Francesca Mastropasqua,Gian Marco Prazzoli,Ernesto Picardi,Carmela Gissi,David S. Horner,Aurelio Reyes,Elisabetta Sbisà,Apollonia Tullo,Graziano Pesole +15 more
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References
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Mutant mitochondrial thymidine kinase in mitochondrial DNA depletion myopathy
TL;DR: Mutations in TK2 represent a new etiology for mitochondrial DNA depletion, underscoring the importance of the mitochondrial dNTP pool in the pathogenesis of mitochondrial depletion.
Journal ArticleDOI
Statin-associated myopathy with normal creatine kinase levels.
Paul S. Phillips,Richard H. Haas,Sergei Bannykh,Stephanie Hathaway,Nancy L Gray,Bruce J. Kimura,Georgirene D. Vladutiu,John D.F. England +7 more
TL;DR: It appears that muscle symptoms of some patients receiving statin therapy might represent a muscle toxicity below the threshold needed to increase creatine kinase levels, which could rule out statin-associated myopathy in patients with muscle symptoms.
Journal ArticleDOI
POLG mutations associated with Alpers' syndrome and mitochondrial DNA depletion
Robert K. Naviaux,Khue Vu Nguyen +1 more
TL;DR: In two unrelated pedigrees of Alpers' syndrome, each affected child was found to carry a homozygous mutation in exon 17 of the POLG locus that led to a Glu873Stop mutation just upstream of the polymerase domain of the protein.
Book
Pathology of Skeletal Muscle
TL;DR: This book is a detailed yet practical, up-to-date text of human muscle pathology that not only describes but extensively and beautifully illustrates human myopathology.
Journal ArticleDOI
Role of mitochondrial DNA mutations in human aging: implications for the central nervous system and muscle.
Elizabeth J. Brierley,Margaret A. Johnson,Robert N. Lightowlers,Oliver F. W. James,Douglass M. Turnbull +4 more
TL;DR: These studies show a direct age‐related correlation between a biochemical and genetic defect in normal human tissues and that mtDNA abnormalities are involved in the aging process in human muscle.
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