mitochondrial myopathies

Summary

Summary: A group of muscle diseases associated with abnormal mitochondria function.

Top Publications

  1. Lalani S, Vladutiu G, Plunkett K, Lotze T, Adesina A, Scaglia F. Isolated mitochondrial myopathy associated with muscle coenzyme Q10 deficiency. Arch Neurol. 2005;62:317-20 pubmed
    ..Primary coenzyme Q(10) (CoQ(10)) deficiency is rare. The encephalomyopathic form, described in few families, is characterized by exercise intolerance, recurrent myoglobinuria, developmental delay, ataxia, and seizures...
  2. DiMauro S. Mitochondrial myopathies. Curr Opin Rheumatol. 2006;18:636-41 pubmed
    ..In this review, I will give the latest information on disorders affecting predominantly or exclusively skeletal muscle...
  3. Taivassalo T, Haller R. Exercise and training in mitochondrial myopathies. Med Sci Sports Exerc. 2005;37:2094-101 pubmed
    ..Although considerable progress has been made, an immediate urgency exists to resolve the effects of chronic exercise on skeletal muscle in patients with heteroplasmic mtDNA mutations...
  4. Mancuso M, Orsucci D, Logerfo A, Rocchi A, Petrozzi L, Nesti C, et al. Oxidative stress biomarkers in mitochondrial myopathies, basally and after cysteine donor supplementation. J Neurol. 2010;257:774-81 pubmed publisher
    ..Oxidative stress biomarkers may be useful to detect redox imbalance in mitochondrial diseases and to provide non-invasive tools to monitor disease status...
  5. Kollberg G, Tulinius M, Melberg A, Darin N, Andersen O, Holmgren D, et al. Clinical manifestation and a new ISCU mutation in iron-sulphur cluster deficiency myopathy. Brain. 2009;132:2170-9 pubmed publisher
    ..There was only a slight reduction of mitochondrial IscU in the compound heterozygotes, despite their severe phenotype, indicating that the IscU expressed in these patients is non-functional...
  6. Shipton E, Prosser D. Mitochondrial myopathies and anaesthesia. Eur J Anaesthesiol. 2004;21:173-8 pubmed
    The mitochondrial myopathies consist of a heterogeneous group of disorders caused by structural and functional abnormalities in mitochondria leading to involvement of the nervous system and muscles as well as other organ systems...
  7. Taivassalo T, Jensen T, Kennaway N, DiMauro S, Vissing J, Haller R. The spectrum of exercise tolerance in mitochondrial myopathies: a study of 40 patients. Brain. 2003;126:413-23 pubmed
    ..In patients with mtDNA mutations, muscle mutation load governs mitochondrial capacity for oxidative phosphorylation and determines exercise capacity...
  8. Koga A, Koga Y, Akita Y, Fukiyama R, Ueki I, Yatsuga S, et al. Increased mitochondrial processing intermediates associated with three tRNA(Leu(UUR)) gene mutations. Neuromuscul Disord. 2003;13:259-62 pubmed
  9. Aure K, Fayet G, Leroy J, Lacene E, Romero N, Lombes A. Apoptosis in mitochondrial myopathies is linked to mitochondrial proliferation. Brain. 2006;129:1249-59 pubmed
    ..It is tightly linked to mitochondrial proliferation and high mutation load. When considering training therapeutics, one will have to take into account the possibility to induce apoptosis in parallel to mitochondrial proliferation...

More Information

Publications60

  1. Spinazzola A, Marti R, Nishino I, Andreu A, Naini A, Tadesse S, et al. Altered thymidine metabolism due to defects of thymidine phosphorylase. J Biol Chem. 2002;277:4128-33 pubmed
    ..We hypothesize that excess thymidine alters mitochondrial nucleoside and nucleotide pools leading to impaired mitochondrial DNA replication, repair, or both. Therapies to reduce thymidine levels may be beneficial to MNGIE patients...
  2. Mochel F, Knight M, Tong W, Hernandez D, Ayyad K, Taivassalo T, et al. Splice mutation in the iron-sulfur cluster scaffold protein ISCU causes myopathy with exercise intolerance. Am J Hum Genet. 2008;82:652-60 pubmed publisher
    ..ISCU interacts with the Friedreich ataxia gene product frataxin in iron-sulfur cluster biosynthesis. Our results therefore extend the range of known human diseases that are caused by defects in iron-sulfur cluster biogenesis...
  3. Di Fonzo A, Ronchi D, Lodi T, Fassone E, Tigano M, Lamperti C, et al. The mitochondrial disulfide relay system protein GFER is mutated in autosomal-recessive myopathy with cataract and combined respiratory-chain deficiency. Am J Hum Genet. 2009;84:594-604 pubmed publisher
    ..These findings shed light on the mechanisms of mitochondrial biogenesis, establish the role of GFER in the human DRS, and promote an understanding of the pathogenesis of a new mitochondrial disease...
  4. Wibrand F, Jeppesen T, Frederiksen A, Olsen D, Duno M, Schwartz M, et al. Limited diagnostic value of enzyme analysis in patients with mitochondrial tRNA mutations. Muscle Nerve. 2010;41:607-13 pubmed publisher
    ..The results indicate that RC enzyme analysis in muscle is not a sensitive test for MM in adults. In these patients, abnormal muscle histochemistry appears to be a better predictor ofMM...
  5. Bykhovskaya Y, Casas K, Mengesha E, Inbal A, Fischel Ghodsian N. Missense mutation in pseudouridine synthase 1 (PUS1) causes mitochondrial myopathy and sideroblastic anemia (MLASA). Am J Hum Genet. 2004;74:1303-8 pubmed
    ..Identification of the pathophysiologic pathways of the mutation in these families may shed light on the tissue specificity of oxidative phosphorylation disorders...
  6. Tarnopolsky M, Raha S. Mitochondrial myopathies: diagnosis, exercise intolerance, and treatment options. Med Sci Sports Exerc. 2005;37:2086-93 pubmed
    b>Mitochondrial myopathies are caused by genetic mutations that directly influence the functioning of the electron transport chain (ETC)...
  7. Filosto M, Mancuso M, Vives Bauza C, Vila M, Shanske S, Hirano M, et al. Lack of paternal inheritance of muscle mitochondrial DNA in sporadic mitochondrial myopathies. Ann Neurol. 2003;54:524-6 pubmed
    ..We did not observe paternal inheritance in any of our patients...
  8. Wong L. Recognition of mitochondrial DNA deletion syndrome with non-neuromuscular multisystemic manifestation. Genet Med. 2001;3:399-404 pubmed
    ..To correlate the molecular characteristics of the mtDNA deletions with clinical phenotypes...
  9. Diaz F, Thomas C, Garcia S, Hernandez D, Moraes C. Mice lacking COX10 in skeletal muscle recapitulate the phenotype of progressive mitochondrial myopathies associated with cytochrome c oxidase deficiency. Hum Mol Genet. 2005;14:2737-48 pubmed
    ..This COX10 KO mouse allowed us to correlate the muscle function with residual COX activity, an estimate that can help predict the progression pattern of human mitochondrial myopathies.
  10. Jensen T, Kazemi Esfarjani P, Skomorowska E, Vissing J. A forearm exercise screening test for mitochondrial myopathy. Neurology. 2002;58:1533-8 pubmed
    ..The authors hypothesized that impaired oxygen extraction in mitochondrial myopathy (MM) results in a high oxygen saturation in venous effluent blood from working muscle and that this phenomenon can be used as a diagnostic tool for MM...
  11. Siciliano G, Simoncini C, Lo Gerfo A, Orsucci D, Ricci G, Mancuso M. Effects of aerobic training on exercise-related oxidative stress in mitochondrial myopathies. Neuromuscul Disord. 2012;22 Suppl 3:S172-7 pubmed publisher
    In mitochondrial myopathies with respiratory chain deficiency impairment of energy cell production may lead to in excess reactive oxygen species generation with consequent oxidative stress and cell damage...
  12. Cejudo P, Bautista J, Montemayor T, Villagomez R, Jimenez L, Ortega F, et al. Exercise training in mitochondrial myopathy: a randomized controlled trial. Muscle Nerve. 2005;32:342-50 pubmed
    Patients with mitochondrial myopathies (MM) usually suffer from exercise intolerance due to their impaired oxidative capacity and physical deconditioning...
  13. Jeppesen T, Olsen D, Vissing J. Cycle ergometry is not a sensitive diagnostic test for mitochondrial myopathy. J Neurol. 2003;250:293-9 pubmed
    ..Cycle testing of MM patients remains an important research tool, but should not be a standard diagnostic procedure for MM...
  14. Durham S, Bonilla E, Samuels D, DiMauro S, Chinnery P. Mitochondrial DNA copy number threshold in mtDNA depletion myopathy. Neurology. 2005;65:453-5 pubmed
    ..This defines the minimum amount of wild-type mtDNA molecules required to maintain COX activity in skeletal muscle and provides an explanation for the mosaic histochemical pattern seen in patients with mtDNA depletion syndrome...
  15. Patton J, Bykhovskaya Y, Mengesha E, Bertolotto C, Fischel Ghodsian N. Mitochondrial myopathy and sideroblastic anemia (MLASA): missense mutation in the pseudouridine synthase 1 (PUS1) gene is associated with the loss of tRNA pseudouridylation. J Biol Chem. 2005;280:19823-8 pubmed
    ..MLASA is thus associated with absent or greatly reduced tRNA pseudouridylation at specific sites, implicating this pathway in its molecular pathogenesis...
  16. Elson J, Samuels D, Johnson M, Turnbull D, Chinnery P. The length of cytochrome c oxidase-negative segments in muscle fibres in patients with mtDNA myopathy. Neuromuscul Disord. 2002;12:858-64 pubmed
    ..The findings have important implications for our understanding of the pathogenesis and progression of mitochondrial DNA myopathy...
  17. Oldfors A, Moslemi A, Jonasson L, Ohlsson M, Kollberg G, Lindberg C. Mitochondrial abnormalities in inclusion-body myositis. Neurology. 2006;66:S49-55 pubmed
    ..Treatment that has positive effects in mitochondrial myopathies may be tried also in s-IBM.
  18. Jeppesen T, Schwartz M, Olsen D, Wibrand F, Krag T, Dunø M, et al. Aerobic training is safe and improves exercise capacity in patients with mitochondrial myopathy. Brain. 2006;129:3402-12 pubmed
    ..Regular, supervised aerobic exercise is therefore recommended in MM patients with the studied mutations...
  19. Taivassalo T, Gardner J, Taylor R, Schaefer A, Newman J, Barron M, et al. Endurance training and detraining in mitochondrial myopathies due to single large-scale mtDNA deletions. Brain. 2006;129:3391-401 pubmed
    At present there are limited therapeutic interventions for patients with mitochondrial myopathies. Exercise training has been suggested as an approach to improve physical capacity and quality of life but it is uncertain whether it offers ..
  20. Quinzii C, Hirano M. Coenzyme Q and mitochondrial disease. Dev Disabil Res Rev. 2010;16:183-8 pubmed publisher
    ..In vitro and in vivo studies are necessary to further understand the pathogenesis of the disease and to develop more effective therapies...
  21. Murphy J, Ratnaike T, Shang E, Falkous G, Blakely E, Alston C, et al. Cytochrome c oxidase-intermediate fibres: importance in understanding the pathogenesis and treatment of mitochondrial myopathy. Neuromuscul Disord. 2012;22:690-8 pubmed publisher
    ..Assessing changes in intermediate fibres will be crucial to evaluating the responses to treatment and in particular to exercise training regimes in patients with mitochondrial DNA disease...
  22. Blakely E, He L, Gardner J, Hudson G, Walter J, Hughes I, et al. Novel mutations in the TK2 gene associated with fatal mitochondrial DNA depletion myopathy. Neuromuscul Disord. 2008;18:557-60 pubmed publisher
    ..Sequencing of the thymidine kinase 2 (TK2) gene revealed two, novel heterozygous mutations (p.Q87X and p.N100S) with parental DNA analysis confirming the transmission of mutated alleles...
  23. Spinazzola A, Invernizzi F, Carrara F, Lamantea E, Donati A, DiRocco M, et al. Clinical and molecular features of mitochondrial DNA depletion syndromes. J Inherit Metab Dis. 2009;32:143-58 pubmed publisher
    ..Five of our patients carried previously unreported mutations in one of the eight MDS genes...
  24. Crooks D, Ghosh M, Haller R, Tong W, Rouault T. Posttranslational stability of the heme biosynthetic enzyme ferrochelatase is dependent on iron availability and intact iron-sulfur cluster assembly machinery. Blood. 2010;115:860-9 pubmed publisher
    ..We propose that decreased heme biosynthesis resulting from impaired Fe-S cluster assembly can contribute to the pathogenesis of diseases caused by defective Fe-S cluster biogenesis...
  25. Hassani A, Horvath R, Chinnery P. Mitochondrial myopathies: developments in treatment. Curr Opin Neurol. 2010;23:459-65 pubmed publisher
    Treatment options for mitochondrial myopathies remain limited despite rapid advances in the understanding of the molecular basis of these conditions...
  26. Pfeffer G, Chinnery P. Diagnosis and treatment of mitochondrial myopathies. Ann Med. 2013;45:4-16 pubmed publisher
    ..readership and provides a clinical approach to the recognition, investigation, and treatment of mitochondrial myopathies. Emphasis is placed on practical management considerations while including some recent updates in the ..
  27. van den Bosch B, de Coo I, Hendrickx A, Busch H, de Jong G, Scholte H, et al. Increased risk for cardiorespiratory failure associated with the A3302G mutation in the mitochondrial DNA encoded tRNALeu(UUR) gene. Neuromuscul Disord. 2004;14:683-8 pubmed
    ..Our findings suggest that a high mutation load of the A3302G mutation can lead to fatal cardiorespiratory failure, likely triggered by low environmental oxygen pressure and exercise...
  28. Vallance H, Jeven G, Wallace D, Brown M. A case of sporadic infantile histiocytoid cardiomyopathy caused by the A8344G (MERRF) mitochondrial DNA mutation. Pediatr Cardiol. 2004;25:538-40 pubmed
    ..To our knowledge, this is the first description of the A8344G mtDNA mutation presenting as a sporadic case of fatal infantile cardiomyopathy and the first occurrence of this mutation associated with histiocytoid cardiomyopathy...
  29. Kornblum C, Schroder R, Muller K, Vorgerd M, Eggers J, Bogdanow M, et al. Creatine has no beneficial effect on skeletal muscle energy metabolism in patients with single mitochondrial DNA deletions: a placebo-controlled, double-blind 31P-MRS crossover study. Eur J Neurol. 2005;12:300-9 pubmed
    ..Cr supplementation did not improve skeletal muscle oxidative phosphorylation in our series of patients. However, one explanation for our negative findings may be the short study duration or the limited number of patients included...
  30. He L, Chinnery P, Durham S, Blakely E, Wardell T, Borthwick G, et al. Detection and quantification of mitochondrial DNA deletions in individual cells by real-time PCR. Nucleic Acids Res. 2002;30:e68 pubmed
  31. Murphy J, Blakely E, Schaefer A, He L, Wyrick P, Haller R, et al. Resistance training in patients with single, large-scale deletions of mitochondrial DNA. Brain. 2008;131:2832-40 pubmed publisher
  32. DiMauro S. Pathogenesis and treatment of mitochondrial myopathies: recent advances. Acta Myol. 2010;29:333-8 pubmed
  33. Alberio S, Mineri R, Tiranti V, Zeviani M. Depletion of mtDNA: syndromes and genes. Mitochondrion. 2007;7:6-12 pubmed
  34. Saada A, Shaag A, Mandel H, Nevo Y, Eriksson S, Elpeleg O. Mutant mitochondrial thymidine kinase in mitochondrial DNA depletion myopathy. Nat Genet. 2001;29:342-4 pubmed publisher
    ..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...
  35. Taivassalo T, Abbott A, Wyrick P, Haller R. Venous oxygen levels during aerobic forearm exercise: An index of impaired oxidative metabolism in mitochondrial myopathy. Ann Neurol. 2002;51:38-44 pubmed
    A cardinal feature of impaired skeletal muscle oxidative metabolism in mitochondrial myopathies is a limited ability to increase the extraction of O(2) from blood relative to the increase in O(2) delivery by the circulation during ..
  36. Sasarman F, Karpati G, Shoubridge E. Nuclear genetic control of mitochondrial translation in skeletal muscle revealed in patients with mitochondrial myopathy. Hum Mol Genet. 2002;11:1669-81 pubmed
    ..These results suggest a defect in a developmentally regulated nuclear factor important for mitochondrial translation in skeletal muscle...
  37. Hammarén E, Rafsten L, Kreuter M, Lindberg C. Modified exercise test in screening for mitochondrial myopathies--adjustment of workload in relation to muscle strength. Eur Neurol. 2004;51:38-41 pubmed
    ..ergometer test, the subanaerobic threshold exercise test (SATET), as a screening test for patients with mitochondrial myopathies. Since the original SATET is frequently found to be strenuous for weak patients, a new variable (relative ..
  38. Siciliano G, Manca M, Renna M, Prontera C, Mercuri A, Murri L. Effects of aerobic training on lactate and catecholaminergic exercise responses in mitochondrial myopathies. Neuromuscul Disord. 2000;10:40-5 pubmed
    ..of an aerobic training program on the metabolic and sympathetic responses to exercise in 12 patients with mitochondrial myopathies. A 10-week course of aerobic training, consisting of supervised exercise every other day on an ..
  39. Rossmanith W, Karwan R. Impairment of tRNA processing by point mutations in mitochondrial tRNA(Leu)(UUR) associated with mitochondrial diseases. FEBS Lett. 1998;433:269-74 pubmed
  40. Koehler C, Leuenberger D, Merchant S, Renold A, Junne T, Schatz G. Human deafness dystonia syndrome is a mitochondrial disease. Proc Natl Acad Sci U S A. 1999;96:2141-6 pubmed
    ..The deafness dystonia syndrome thus is a novel type of mitochondrial disease that probably is caused by a defective mitochondrial protein-import system...
  41. Siciliano G, Renna M, Manca M, Prontera C, Zucchelli G, Ferrannini E, et al. The relationship of plasma catecholamine and lactate during anaerobic threshold exercise in mitochondrial myopathies. Neuromuscul Disord. 1999;9:411-6 pubmed
    ..In order to assess the role of such activation in mitochondrial myopathies, we compared blood catecholamine levels to those of lactate during an intermittent exercise performed at ..
  42. Bonnet D, Martin D, Pascale De Lonlay -, Villain E, Jouvet P, Rabier D, et al. Arrhythmias and conduction defects as presenting symptoms of fatty acid oxidation disorders in children. Circulation. 1999;100:2248-53 pubmed
    ..They may present as isolated cardiomyopathy, sudden death, progressive skeletal myopathy, or hepatic failure. Arrhythmia is an unusual presenting symptom of fatty acid oxidation deficiencies...
  43. Klopstock T, Querner V, Schmidt F, Gekeler F, Walter M, Hartard M, et al. A placebo-controlled crossover trial of creatine in mitochondrial diseases. Neurology. 2000;55:1748-51 pubmed
    ..Cr was well tolerated, but there were no significant effects with regard to exercise performance, eye movements, or activities of daily life. The power of this pilot study was limited and future multicenter trials are needed...
  44. Vissing J, Gansted U, Quistorff B. Exercise intolerance in mitochondrial myopathy is not related to lactic acidosis. Ann Neurol. 2001;49:672-6 pubmed
    ..This indicates that lactate acidosis is not the primary cause of exercise intolerance in MM...
  45. Hameed R, Raafat F, Ramani P, Gray G, Roper H, Milford D. Mitochondrial cytopathy presenting with focal segmental glomerulosclerosis, hypoparathyroidism, sensorineural deafness, and progressive neurological disease. Postgrad Med J. 2001;77:523-6 pubmed
    ..He later developed progressive neurological deterioration and mitochondrial myopathy and neuropathy was diagnosed...
  46. Yasukawa T, Suzuki T, Ishii N, Ueda T, Ohta S, Watanabe K. Defect in modification at the anticodon wobble nucleotide of mitochondrial tRNA(Lys) with the MERRF encephalomyopathy pathogenic mutation. FEBS Lett. 2000;467:175-8 pubmed
    ..We therefore suggest the defect in the anticodon is responsible, through the translational process, for the pathogenesis of mitochondrial diseases...
  47. Fosslien E. Mitochondrial medicine--molecular pathology of defective oxidative phosphorylation. Ann Clin Lab Sci. 2001;31:25-67 pubmed
    ..Oral Q10 supplementation is effective in treating cardiomyopathies and in restoring plasma levels reduced by the statin type of cholesterol-lowering drugs...
  48. Ibel H, Endres W, Hadorn H, Deufel T, Paetzke I, Duran M, et al. Multiple respiratory chain abnormalities associated with hypertrophic cardiomyopathy and 3-methylglutaconic aciduria. Eur J Pediatr. 1993;152:665-70 pubmed
  49. Taivassalo T, Shoubridge E, Chen J, Kennaway N, DiMauro S, Arnold D, et al. Aerobic conditioning in patients with mitochondrial myopathies: physiological, biochemical, and genetic effects. Ann Neurol. 2001;50:133-41 pubmed
    Aerobic training has been shown to increase work and oxidative capacity in patients with mitochondrial myopathies, but the mechanisms underlying improvement are not known...
  50. Lightowlers R, Chinnery P, Turnbull D, Howell N. Mammalian mitochondrial genetics: heredity, heteroplasmy and disease. Trends Genet. 1997;13:450-5 pubmed
  51. Gilbert R, Emms M. Pearson's syndrome presenting with Fanconi syndrome. Ultrastruct Pathol. 1996;20:473-5 pubmed
    ..The dominant clinical feature was a generalized disorder of proximal tubule function with severe renal magnesium wasting. Renal and muscle biopsies were performed and showed bizarre giant mitochondria...