Diagnosis and treatment of mitochondrial myopathies

References

• Chinnery PF, DiMauro S, Shanske S, , SchonEAZeviani M, Mariotti C, . Risk of developing a mitochondrial DNA deletion disorder. Lancet. 2004;364:592–6.
   PubMed Web of Science ®Google Scholar
• Chinnery PF, Thorburn DR, Samuels DC, White SL, Dahl HM, Turnbull DM, . The inheritance of mitochondrial DNA heteroplasmy: random drift, selection or both? Trends Genet. 2000;16:500–5.
   PubMed Web of Science ®Google Scholar
• Mattson MP, Gleichmann M, Cheng A. Mitochondria in neuroplasticity and neurological disorders. Neuron. 2008; 60:748–66.
   PubMed Web of Science ®Google Scholar
• Sarnat HB, Marin-Garcia J. Pathology of mitochondrial encephalomyopathies. Can J Neurol Sci. 2005;32:152–66.
   PubMed Web of Science ®Google Scholar
• Schaefer AM, McFarland R, Blakely EL, He L, Whittaker RG, Taylor RW, . Prevalence of mitochondrial DNA disease in adults. Ann Neurol. 2008;63:35–9.
   PubMed Web of Science ®Google Scholar
• Elliott HR, Samuels DC, Eden JA, Relton CL, Chinnery PF. Pathogenic mitochondrial DNA mutations are common in the general population. Am J Hum Genet. 2008;83:254–60.
   PubMed Web of Science ®Google Scholar
• Schapira AH. Mitochondrial disease. Lancet. 2006;368:70–82.
   PubMed Web of Science ®Google Scholar
• Yu Wai Man CY, Smith T, Chinnery PF, Turnbull DM, Griffiths PG. Assessment of visual function in chronic progressive external ophthalmoplegia. Eye. 2006;20:564–8.
   PubMed Web of Science ®Google Scholar
• Pfeffer G, Sirrs S, Wade NK, Mezei MM. Multisystem disorder in late-onset chronic progressive external ophthalmoplegia. Can J Neurol Sci. 2011;38:119–23.
   PubMed Web of Science ®Google Scholar
• Mimaki M, Hatakeyama H, Komaki H, Yokoyama M, Arai H, Kirino Y, . Reversible infantile respiratory chain deficiency: a clinical and molecular study. Ann Neurol. 2010;68: 845–54.
   PubMed Web of Science ®Google Scholar
• Horvath R, Kemp JP, Tuppen HA, Hudson G, Oldfors A, Marie SK, . Molecular basis of infantile reversible cytochrome c oxidase deficiency myopathy. Brain. 2009; 132(Pt 11):3165–74.
   PubMedGoogle Scholar
• Rotig A, Appelkvist EL, Geromel V, Chretien D, Kadhom N, Edery P, . Quinone-responsive multiple respiratory-chain dysfunction due to widespread coenzyme Q10 deficiency. Lancet. 2000;356:391–5.
   PubMed Web of Science ®Google Scholar
• Salviati L, Sacconi S, Murer L, Zacchello G, Franceschini L, Laverda AM, . Infantile encephalomyopathy and nephropathy with CoQ10 deficiency: a CoQ10-responsive condition. Neurology. 2005;65:606–8.
   PubMed Web of Science ®Google Scholar
• Gempel K, Topaloglu H, Talim B, Schneiderat P, Schoser BG, Hans VH, . The myopathic form of coenzyme Q10 deficiency is caused by mutations in the electron-transferring-flavoprotein dehydrogenase (ETFDH) gene. Brain. 2007; 130(Pt 8):2037–44.
   PubMedGoogle Scholar
• Lalani SR, Vladutiu GD, Plunkett K, Lotze TE, Adesina AM, Scaglia F. Isolated mitochondrial myopathy associated with muscle coenzyme Q10 deficiency. Arch Neurol. 2005; 62:317–20.
   PubMedGoogle Scholar
• Ogasahara S, Engel AG, Frens D, Mack D. Muscle coenzyme Q deficiency in familial mitochondrial encephalomyopathy. Proc Natl Acad Sci U S A. 1989;86:2379–82.
   PubMed Web of Science ®Google Scholar
• Giordano C, Pichiorri F, Blakely EL, Perli E, Orlandi M, Gallo P, . Isolated distal myopathy of the upper limbs associated with mitochondrial DNA depletion and polymerase gamma mutations. Arch Neurol. 2010;67:1144–6.
   PubMedGoogle Scholar
• Moraes CT, Ciacci F, Silvestri G, Shanske S, Sciacco M, Hirano M, . Atypical clinical presentations associated with the MELAS mutation at position 3243 of human mitochondrial DNA. Neuromuscul Disord. 1993;3:43–50.
   PubMed Web of Science ®Google Scholar
• Taylor RW, Schaefer AM, Barron MJ, McFarland R, Turnbull DM. The diagnosis of mitochondrial muscle disease. Neuromuscul Disord. 2004;14:237–45.
   PubMed Web of Science ®Google Scholar
• Bernier FP, Boneh A, Dennett X, Chow CW, Cleary MA, Thorburn DR. Diagnostic criteria for respiratory chain disorders in adults and children. Neurology. 2002;59:1406–11.
   PubMed Web of Science ®Google Scholar
• Schaefer AM, Blakely EL, Griffiths PG, Turnbull DM, Taylor RW. Ophthalmoplegia due to mitochondrial DNA disease: the need for genetic diagnosis. Muscle Nerve. 2005; 321:104–7.
   Google Scholar
• Greaves LC, Yu-Wai-Man P, Blakely EL, Krishnan KJ, Beadle NE, Kerin J, . Mitochondrial DNA defects and selective extraocular muscle involvement in CPEO. Invest Ophthalmol Vis Sci. 2010;51:3340–6.
   PubMed Web of Science ®Google Scholar
• Eshaghian J, Anderson RL, Weingeist TA, Hart MN, Cancilla PA. Orbicularis oculi muscle in chronic progressive external ophthalmoplegia. Arch Ophthalmol. 1980;98:1070–3.
   PubMedGoogle Scholar
• Almousa R, Charlton A, Rajesh ST, Sundar G, Amrith S. Optimizing muscle biopsy for the diagnosis of mitochondrial myopathy. Ophthal Plast Reconstr Surg. 2009;25:366–70.
   PubMed Web of Science ®Google Scholar
• Wibrand F, Jeppesen TD, Frederiksen AL, Olsen DB, Duno M, Schwartz M, . Limited diagnostic value of enzyme analysis in patients with mitochondrial tRNA mutations. Muscle Nerve. 2010;41:607–13.
   PubMed Web of Science ®Google Scholar
• Medja F, Allouche S, Frachon P, Jardel C, Malgat M, Mousson de Camaret B, . Development and implementation of standardized respiratory chain spectrophotometric assays for clinical diagnosis. Mitochondrion. 2009;9:331–9.
   PubMed Web of Science ®Google Scholar
• Hasegawa H, Matsuoka T, Goto Y, Nonaka I. Strongly succinate dehydrogenase-reactive blood vessels in muscles from patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes. Ann Neurol. 1991;29: 601–5.
   PubMed Web of Science ®Google Scholar
• Milone M, Massie R. Polymerase gamma 1 mutations: clinical correlations. Neurologist. 2010;16:84–91.
   PubMed Web of Science ®Google Scholar
• Whittaker RG, Blackwood JK, Alston CL, Blakely EL, Elson JL, McFarland R, . Urine heteroplasmy is the best predictor of clinical outcome in the m.3243A >G mtDNA mutation. Neurology. 2009;72:568–9.
   PubMed Web of Science ®Google Scholar
• DiMauro S, Schon EA. Mitochondrial DNA mutations in human disease. Am J Med Genet. 2001;106:18–26.
   PubMed Web of Science ®Google Scholar
• van den Heuvel LP, Smeitink JA, Rodenburg RJ. Biochemical examination of fibroblasts in the diagnosis and research of oxidative phosphorylation (OXPHOS) defects. Mitochondrion. 2004;4:395–401.
   PubMed Web of Science ®Google Scholar
• Tarnopolsky M. Exercise testing as a diagnostic entity in mitochondrial myopathies. Mitochondrion. 2004;4:529–42.
   PubMed Web of Science ®Google Scholar
• Dandurand RJ, Matthews PM, Arnold DL, Eidelman DH. Mitochondrial disease. Pulmonary function, exercise performance, and blood lactate levels. Chest. 1995;108:182–9.
   PubMed Web of Science ®Google Scholar
• Hammaren 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 Web of Science ®Google Scholar
• Jeppesen TD, Olsen D, Vissing J. Cycle ergometry is not a sensitive diagnostic test for mitochondrial myopathy. J Neurol. 2003;250:293–9.
   PubMed Web of Science ®Google Scholar
• Jensen TD, Kazemi-Esfarjani P, Skomorowska E, Vissing J. A forearm exercise screening test for mitochondrial myopathy. Neurology. 2002;58:1533–8.
   PubMed Web of Science ®Google Scholar
• Taivassalo T, Abbott A, Wyrick P, Haller RG. Venous oxygen levels during aerobic forearm exercise: An index of impaired oxidative metabolism in mitochondrial myopathy. Ann Neurol. 2002;51:38–44.
   PubMed Web of Science ®Google Scholar
• Gimenes AC, Napolis LM, Silva NL, Siquiera GO, Bulle AS, Neder JA, . The effect of L-carnitine supplementation on respiratory muscle strength and exercise tolerance in patients with mitochondrial myopathies. [Abstract]. Eur Respir J 2007;51(Suppl):21S[E297].
   Google Scholar
• Kornblum C, Schroder R, Muller K, Vorgerd M, Eggers J, Bogdanow M, . 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 Web of Science ®Google Scholar
• Klopstock T, Querner V, Schmidt F, Gekeler F, Walter M, Hartard M, . A placebo-controlled crossover trial of creatine in mitochondrial diseases. Neurology. 2000;55: 1748–51.
   PubMed Web of Science ®Google Scholar
• Tarnopolsky MA, Roy BD, MacDonald JR. A randomized, controlled trial of creatine monohydrate in patients with mitochondrial cytopathies. Muscle Nerve. 1997;20:1502–9.
   PubMed Web of Science ®Google Scholar
• Stacpoole PW, Kerr DS, Barnes C, Bunch ST, Carney PR, Fennell EM, . Controlled clinical trial of dichloroacetate for treatment of congenital lactic acidosis in children. Pediatrics. 2006;117:1519–31.
   PubMed Web of Science ®Google Scholar
• Bresolin N, Doriguzzi C, Ponzetto C, Angelini C, Moroni I, Castelli E, . Ubidecarenone in the treatment of mitochondrial myopathies: a multi-center double-blind trial. J Neurol Sci. 1990;100:70–8.
   PubMed Web of Science ®Google Scholar
• Mancuso M, Orsucci D, Logerfo A, Rocchi A, Petrozzi L, Nesti C, . Oxidative stress biomarkers in mitochondrial myopathies, basally and after cysteine donor supplementation. J Neurol. 2010;257:774–81.
   PubMed Web of Science ®Google Scholar
• Kaufmann P, Engelstad K, Wei Y, Jhung S, Sano MC, Shungu DC, . Dichloroacetate causes toxic neuropathy in MELAS: a randomized, controlled clinical trial. Neurology. 2006;66:324–30.
   PubMed Web of Science ®Google Scholar
• De Stefano N, Matthews PM, Ford B, Genge A, Karpati G, Arnold DL. Short-term dichloroacetate treatment improves indices of cerebral metabolism in patients with mitochondrial disorders. Neurology. 1995;45:1193–8.
   PubMed Web of Science ®Google Scholar
• Vissing J, Gansted U, Quistorff B. Exercise intolerance in mitochondrial myopathy is not related to lactic acidosis. Ann Neurol. 2001;49:672–6.
   PubMed Web of Science ®Google Scholar
• Duncan GE, Perkins LA, Theriaque DW, Neiberger RE, Stacpoole PW. Dichloroacetate therapy attenuates the blood lactate response to submaximal exercise in patients with defects in mitochondrial energy metabolism. J Clin Endocrinol Metab. 2004;89:1733–8.
   PubMed Web of Science ®Google Scholar
• Liet JM, Pelletier V, Robinson BH, Laryea MD, Wendel U, Morneau S, . The effect of short-term dimethylglycine treatment on oxygen consumption in cytochrome oxidase deficiency: a double-blind randomized crossover clinical trial. J Pediatr. 2003;142:62–6.
   PubMed Web of Science ®Google Scholar
• Rodriguez MC, MacDonald JR, Mahoney DJ, Parise G, Beal MF, Tarnopolsky MA. Beneficial effects of creatine, CoQ10, and lipoic acid in mitochondrial disorders. Muscle Nerve. 2007;35:235–42.
   PubMed Web of Science ®Google Scholar
• Musumeci O, Naini A, Slonim AE, Skavin N, Hadjigeorgiou GL, Krawiecki N, . Familial cerebellar ataxia with muscle coenzyme Q10 deficiency. Neurology. 2001;56:849–55.
   PubMed Web of Science ®Google Scholar
• Montini G, Malaventura C, Salviati L. Early coenzyme Q10 supplementation in primary coenzyme Q10 deficiency. N Engl J Med. 2008;358:2849–50.
   PubMed Web of Science ®Google Scholar
• Ikejiri Y, Mori E, Ishii K, Nishimoto K, Yasuda M, Sasaki M. Idebenone improves cerebral mitochondrial oxidative metabolism in a patient with MELAS. Neurology. 1996;47:583–5.
   PubMed Web of Science ®Google Scholar
• Seki A, Nishino I, Goto Y, Maegaki Y, Koeda T. Mitochondrial encephalomyopathy with 15915 mutation: clinical report. Pediatr Neurol. 1997;17:161–4.
   PubMed Web of Science ®Google Scholar
• Haginoya K, Miyabayashi S, Kikuchi M, Kojima A, Yamamoto K, Omura K, . Efficacy of idebenone for respiratory failure in a patient with Leigh syndrome: a long-term follow-up study. J Neurol Sci. 2009;278:112–4.
   PubMed Web of Science ®Google Scholar
• Hassani A, Horvath R, Chinnery PF. Mitochondrial myopathies: developments in treatment. Curr Opin Neurol. 2010;23:459–65.
   PubMed Web of Science ®Google Scholar
• Wenz T, Diaz F, Hernandez D, Moraes CT. Endurance exercise is protective for mice with mitochondrial myopathy. J Appl Physiol. 2009;106:1712–9.
   PubMed Web of Science ®Google Scholar
• Smith RA, Murphy MP. Animal and human studies with the mitochondria-targeted antioxidant MitoQ. Ann N Y Acad Sci. 2010;1201:96–103.
   PubMed Web of Science ®Google Scholar
• Jeppesen TD, Schwartz M, Olsen DB, Wibrand F, Krag T, Duno M, . Aerobic training is safe and improves exercise capacity in patients with mitochondrial myopathy. Brain. 2006;129(Pt 12):3402–12.
   PubMedGoogle Scholar
• Taivassalo T, De Stefano N, Argov Z, Matthews PM, Chen J, Genge A, . Effects of aerobic training in patients with mitochondrial myopathies. Neurology. 1998;50:1055–60.
   PubMed Web of Science ®Google Scholar
• Taivassalo T, Gardner JL, Taylor RW, Schaefer AM, Newman J, Barron MJ, . Endurance training and detraining in mitochondrial myopathies due to single large-scale mtDNA deletions. Brain. 2006;129(Pt 12):3391–401.
   PubMedGoogle Scholar
• Cejudo P, Bautista J, Montemayor T, Villagomez R, Jimenez L, Ortega F, . Exercise training in mitochondrial myopathy: a randomized controlled trial. Muscle Nerve. 2005;32: 342–50.
   PubMed Web of Science ®Google Scholar
• Murphy JL, Blakely EL, Schaefer AM, He L, Wyrick P, Haller RG, . Resistance training in patients with single, large-scale deletions of mitochondrial DNA. Brain. 2008; 131(Pt 11):2832–40.
   PubMedGoogle Scholar
• Koga Y, Akita Y, Nishioka J, Yatsuga S, Povalko N, Tanabe Y, . L-arginine improves the symptoms of strokelike episodes in MELAS. Neurology. 2005;64:710–2.
   PubMed Web of Science ®Google Scholar
• Arakawa K, Kudo T, Ikawa M, Morikawa N, Kawai Y, Sahashi K, . Abnormal myocardial energy-production state in mitochondrial cardiomyopathy and acute response to L-arginine infusion. C-11 acetate kinetics revealed by positron emission tomography. Circ J. 2010;74:2702–11.
   PubMed Web of Science ®Google Scholar
• Visser NA, Braun KP, Leijten FS, van Nieuwenhuizen O, Wokke JH, van den Bergh WM. Magnesium treatment for patients with refractory status epilepticus due to POLG1-mutations. J Neurol. 2011;258:218–22.
   PubMed Web of Science ®Google Scholar
• Klopstock T, Jaksch M, Gasser T. Age and cause of death in mitochondrial diseases. Neurology. 1999;53:855–7.
   PubMed Web of Science ®Google Scholar
• Baik R, Chae JH, Lee YM, Kang HC, Lee JS, Kim HD. Electrocardiography as an early cardiac screening test in children with mitochondrial disease. Korean J Pediatr. 2010;53:644–7.
   PubMedGoogle Scholar
• Marin-Garcia J, Goldenthal MJ. Mitochondrial cardiomyopathy: molecular and biochemical analysis. Pediatr Cardiol. 1997;18:251–60.
   PubMed Web of Science ®Google Scholar
• Holmgren D, Wahlander H, Eriksson BO, Oldfors A, Holme E, Tulinius M. Cardiomyopathy in children with mitochondrial disease; clinical course and cardiological findings. Eur Heart J. 2003;24:280–8.
   PubMed Web of Science ®Google Scholar
• Jose T, Gdynia HJ, Mahrholdt H, Vohringer M, Klingel K, Kandolf R, . CMR gives clue to “ragged red fibers” in the heart in a patient with mitochondrial myopathy. Int J Cardiol. 2011;149:e24–7.
   PubMed Web of Science ®Google Scholar
• Partington SL, Givertz MM, Gupta S, Kwong RY. Cardiac magnetic resonance AIDS in the diagnosis of mitochondrial cardiomyopathy. Circulation. 2011;123:e227–9.
   PubMed Web of Science ®Google Scholar
• Kaufmann P, Engelstad K, Wei Y, Kulikova R, Oskoui M, Battista V, . Protean phenotypic features of the A3243G mitochondrial DNA mutation. Arch Neurol. 2009;66:85–91.
   PubMedGoogle Scholar
• Cros D, Palliyath S, DiMauro S, Ramirez C, Shamsnia M, Wizer B. Respiratory failure revealing mitochondrial myopathy in adults. Chest. 1992;101:824–8.
   PubMed Web of Science ®Google Scholar
• Manni R, Piccolo G, Banfi P, Cerveri I, Bruschi C, Zoia C, . Respiratory patterns during sleep in mitochondrial myopathies with ophthalmoplegia. Eur Neurol. 1991;31:12–17.
   PubMed Web of Science ®Google Scholar
• Barohn RJ, Clanton T, Sahenk Z, Mendell JR. Recurrent respiratory insufficiency and depressed ventilatory drive complicating mitochondrial myopathies. Neurology. 1990; 40:103–6.
   PubMed Web of Science ®Google Scholar
• Finsterer J, Segall L. Drugs interfering with mitochondrial disorders. Drug Chem Toxicol. 2010;33:138–51.
   PubMed Web of Science ®Google Scholar
• Sirvent P, Bordenave S, Vermaelen M, Roels B, Vassort G, Mercier J, . Simvastatin induces impairment in skeletal muscle while heart is protected. Biochem Biophys Res Commun. 2005;338:1426–34.
   PubMed Web of Science ®Google Scholar
• Bruckert E, Hayem G, Dejager S, Yau C, Begaud B. Mild to moderate muscular symptoms with high-dosage statin therapy in hyperlipidemic patients—the PRIMO study. Cardiovasc Drugs Ther. 2005;19:403–14.
   PubMed Web of Science ®Google Scholar
• Baker SK, Vladutiu GD, Peltier WL, Isackson PJ, Tarnopolsky MA. Metabolic myopathies discovered during investigations of statin myopathy. Can J Neurol Sci. 2008;35:94–7.
   PubMed Web of Science ®Google Scholar
• Elsais A, Lund C, Kerty E. Ptosis, diplopia and statins: an association? Eur J Neurol. 2008;15:e90–1.
   PubMed Web of Science ®Google Scholar
• Fraunfelder FW, Richards AB. Diplopia, blepharoptosis, and ophthalmoplegia and 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitor use. Ophthalmology. 2008;115:2282–5.
   PubMed Web of Science ®Google Scholar
• Venhoff N, Setzer B, Melkaoui K, Walker UA. Mitochondrial toxicity of tenofovir, emtricitabine and abacavir alone and in combination with additional nucleoside reverse transcriptase inhibitors. Antivir Ther. 2007;12:1075–85.
   PubMed Web of Science ®Google Scholar
• Ananworanich J, Nuesch R, Cote HC, Kerr SJ, Hill A, Jupimai T, . Changes in metabolic toxicity after switching from stavudine/didanosine to tenofovir/lamivudine—a Staccato trial substudy. J Antimicrob Chemother. 2008;61:1340–3.
   PubMed Web of Science ®Google Scholar
• Dinges WL, Witherspoon SR, Itani KM, Garg A, Peterson DM. Blepharoptosis and external ophthalmoplegia associated with long-term antiretroviral therapy. Clin Infect Dis. 2008;47:845–52.
   PubMed Web of Science ®Google Scholar
• Zannou DM, Azon-Kouanou A, Bashi BJ, Gougounon A, Zinsou R, Ade G, . Mitochondrial toxicity: a case of palpebral ptosis in a woman infected by HIV and treated with HAART including zidovudine. Bull Soc Pathol Exot. 2009;102:97–8.
   PubMedGoogle Scholar
• Pfeffer G, Cote HC, Montaner JS, Li CC, Jitratkosol M, Mezei MM. Ophthalmoplegia and ptosis: mitochondrial toxicity in patients receiving HIV therapy. Neurology. 2009;73:71–2.
   PubMed Web of Science ®Google Scholar
• Lin CM, Thajeb P. Valproic acid aggravates epilepsy due to MELAS in a patient with an A3243G mutation of mitochondrial DNA. Metab Brain Dis. 2007;22:105–9.
   PubMed Web of Science ®Google Scholar
• Krahenbuhl S, Brandner S, Kleinle S, Liechti S, Straumann D. Mitochondrial diseases represent a risk factor for valproate-induced fulminant liver failure. Liver. 2000;20:346–8.
   PubMedGoogle Scholar
• McFarland R, Hudson G, Taylor RW, Green SH, Hodges S, McKiernan PJ, . Reversible valproate hepatotoxicity due to mutations in mitochondrial DNA polymerase gamma (POLG1). Arch Dis Child. 2008;93:151–3.
   PubMed Web of Science ®Google Scholar
• Stewart JD, Horvath R, Baruffini E, Ferrero I, Bulst S, Watkins PB, . Polymerase gamma gene POLG determines the risk of sodium valproate-induced liver toxicity. Hepatology. 2010;52:1791–6.
   PubMed Web of Science ®Google Scholar
• Eleff S, Kennaway NG, Buist NR, Darley-Usmar VM, Capaldi RA, Bank WJ, . 31PNMR study of improvement in oxidative phosphorylation by vitamins K3 and C in a patient with a defect in electron transport at complex III in skeletal muscle. Proc Natl Acad Sci U S A. 1984;81:3529–33.
   PubMed Web of Science ®Google Scholar
• Mowat D, Kirby DM, Kamath KR, Kan A, Thorburn DR, Christodoulou J. Respiratory chain complex III [correction of complex] in deficiency with pruritus: a novel vitamin responsive clinical feature. J Pediatr. 1999;134:352–4.
   PubMed Web of Science ®Google Scholar
• Panetta J, Smith LJ, Boneh A. Effect of high-dose vitamins, coenzyme Q and high-fat diet in paediatric patients with mitochondrial diseases. J Inherit Metab Dis. 2004;27:487–98.
   PubMed Web of Science ®Google Scholar
• Remes AM, Liimatta EV, Winqvist S, Tolonen U, Ranua JA, Reinikainen K, . Ubiquinone and nicotinamide treatment of patients with the 3243A– > G mtDNA mutation. Neurology. 2002;59:1275–7.
   PubMed Web of Science ®Google Scholar
• Majamaa K, Rusanen H, Remes A, Hassinen IE. Metabolic interventions against complex I deficiency in MELAS syndrome. Mol Cell Biochem. 1997;174:291–6.
   PubMed Web of Science ®Google Scholar
• Penn AM, Lee JW, Thuillier P, Wagner M, Maclure KM, Menard MR, . MELAS syndrome with mitochondrial tRNA(Leu)(UUR) mutation: correlation of clinical state, nerve conduction, and muscle 31P magnetic resonance spectroscopy during treatment with nicotinamide and riboflavin. Neurology. 1992;42:2147–52.
   PubMed Web of Science ®Google Scholar
• Shoffner JM, Lott MT, Voljavec AS, Soueidan SA, Costigan DA, Wallace DC. Spontaneous Kearns-Sayre/chronic external ophthalmoplegia plus syndrome associated with a mitochondrial DNA deletion: a slip-replication model and metabolic therapy. Proc Natl Acad Sci U S A. 1989;86: 7952–6.
   PubMed Web of Science ®Google Scholar
• Oguro H, Iijima K, Takahashi K, Nagai A, Bokura H, Yamaguchi S, . Successful treatment with succinate in a patient with MELAS. Intern Med. 2004;43:427–31.
   PubMed Web of Science ®Google Scholar