Neurologie up2date, Table of Contents Neurologie up2date 2022; 05(01): 73-96DOI: 10.1055/a-1514-2141 Myopathien und Neuropathien Mitochondriale Erkrankungen – Ein Update zu Klinik, Diagnostik und Therapie Authors Author Affiliations Claudia Stendel 1 Friedrich-Baur-Institut, Neurologischen Klinik und Poliklinik der LMU München, München, Deutschland Christiane Michaela Neuhofer 2 Friedrich-Baur-Institut, Neurologischen Klinik und Poliklinik der LMU München, München, Deutschland Thomas Klopstock 3 Friedrich-Baur-Institut, Neurologischen Klinik und Poliklinik der LMU München, München, Deutschland Recommend Article Abstract Buy Article(opens in new window) All articles of this category(opens in new window) Mitochondriale Erkrankungen sind genetisch und klinisch sehr heterogene Krankheitsbilder und gehören zu den häufigsten hereditären Erkrankungen. Aufgrund der Mannigfaltigkeit der Symptome ist der Weg zur korrekten Diagnose oft erschwert und zeitverzögert. In dieser Übersicht werden die typischen Symptome und klassischen Krankheitsbilder sowie aktuelle Therapieoptionen zusammengefasst. Full Text References Literatur 1 Sperl W, Freisinger P. Mitochondriopathien. et al. In: Hoffmann G, Lentze M, Spranger J. Pädiatrie. Springer, Berlin, Heidelberg: Springer Reference Medizin; 2019 2 GENOMIT. Disease Genes. https://genomit.eu/work-packages/integrated-diagnostics/disease-genes/index.html 3 Munnich A, Rötig A, Chretien D. et al. Clinical presentations and laboratory investigations in respiratory chain deficiency. Eur J Pediatr 1996; 155: 262-274 4 Klopstock T, Priglinger C, Yilmaz A. et al. Mitochondriale Erkrankungen. Dtsch Arztebl Int 2021; 118: 741-748 5 Footitt EJ, Sinha MD, Raiman JA. et al. Mitochondrial disorders and general anaesthesia: a case series and review. Br J Anaesth 2008; 100: 436-441 6 Chiaratta MR, Meirelles FV, Wells D. et al. Therapeutic treatments of mtDNA diseases at the earliest stages of human development. Mitochondrion 2011; 11: 820-828 7 Poulton J, Steffann J, Burgstaller J. et al. 234th ENMC international workshop: Developing guidelines for management of reproductive options for families with maternally inherited mtDNA disease; Amsterdam, the Netherlands, 22–24 March 2019. Neuromuscul Disord 2019; 29: 725-733 8 Pickett SJ, Blain A, Ng YS. et al. Mitochondrial donation – which woman could benefit?. N Engl J Med 2019; 380: 1971-1972 9 Schaefer AM, Mcfarland R, Blakely EL. et al. Prevalence of mitochondrial DNA diseas in adults. Ann Neurol 2008; 63: 35-39 10 Rabenstein R, Catarino C, Rampeltshammer V. et al. Smoking and alcohol, health-related quality of life and psychiatric comorbidities in Leber`s Hereditary Optic Neuropathy mutation carriers: a prospective cohort study. Orphanet J Rare Dis 2021; 16: 127 11 Klopstock T, Yu-Wai-Man P, Dimitriadis K. et al. A randomized placebo-controlled trial of idebenone in Leberʼs hereditary optic neuropathy. Brain 2011; 134: 2677-2686 12 Catarino CB, von Livonius B, Priglinger C. et al. Real-world clinical experience with Idebenone in the treatment of Leber Hereditary Optic Neuropathy. J Neuroophthalmol 2020; 40: 558-565 13 Carelli V, Carbonelli M, De Coo IF. et al. International consensus statement on the clinical and therapeutic management of Leber Hereditary Optic Neuropathy. J Neuroophthalmol 2017; 37: 371-381 14 Yu-Wai-Man P, Newman NJ, Carelli V. et al. Bilateral visual improvement with unilateral gene therapy injection for Leber hereditary optic neuropathy. Sci Transl Med 2020; 12: eaaz7423 15 Newmann NJ, Yu-Wai-Man P, Carelli V. et al. Efficacy and safety of intravitreal gene therapy for Leber Hereditary Optic Neuropathy treated within 6 months of disease onset. Ophthalmology 2021; 128: 649-660 16 Holt IJ, Cooper JM, Morgan-Hughes JA. et al. Deletions of muscle mitochondrial DNA. Lancet 1988; 1: 1-462 17 Chinnery PF, DiMauroSShanske S. et al. Risk of developing a mitochondrial DNA deletion disorder. Lancet 2004; 364: 592-596 18 Deschauer M, Zierz S. Defekte der intergenomischen Kommunikation: Mutationen der Kern-DNA und multiple Deletionen der mitochondrialen DNA bei chronisch progressive externer Opthalmoplegie. Akt Neurol 2002; 30: 103-106 19 Fratter C, Raman P, Alston CL. et al. RRM2B mutations are frequent in familial PEO with multiple DNA deletions. Neurology 2011; 76: 2032-2034 20 Ahn J, Kim NJ, Choung HK. et al. Frontalis sling operation using silicone rod for the correction of ptosis in chronic progressive external opthalmoplegia. Br J Ophthalmol 2008; 92: 1685-1688 21 Moraes CT, DiMauro S, Zeviani M. et al. Mitochondrial DNA deletions in progressive external ophthalmoplegia and Kearns-Sayre-Syndrome. N Engl F Med 1989; 320: 1293-1299 22 Pineda M, Ormazábal A, López-Gallardo E. et al. Cerebral folate deficiency and leukoencephalopathy caused by mitochondrial DNA deletion. Ann Neurol 2006; 59: 394-398 23 Ciafaloni E, Ricci E, Shanske S. et al. MELAS: clinical features, biochemistry, and molecular genetics. Ann Neurol 1992; 31: 391-398 24 Lam CW, Lau CH, William JC. et al. Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) triggered by valproate therapy. Eur J Pediatr 1997; 156: 562-564 25 Silvestri G, Ciafaloni E, Santorelli FM. et al. Clinical features associated with the A-- >G transition at nucleotide 8344 of mtDNA (“MERRF mutation). Neurology 1993; 43: 1 200-1206 26 Shoffner JM, Lott MT Lezza AM. et al. Myoclonic epilepsy and ragged-red fiber disease (MERRF) is associated with a mitochondrial DNA tRNA(Lys) mutation. Cell 1990; 61: 931-937 27 Orsucci D, Ienco EC, Siciliano G. et al. Mitochondrial disorders and drugs: what every physician should know. Drugs Context 2019; 8: 212588 28 Holt U, Harding AE, Petty RHK. et al. A new mitochondrial disease associated with mitochondrial DNA heteroplasmy. Am J Hum Genet 1990; 46: 428-433 29 Stendel C, Neuhofer C, Floride E. et al. Delineating MT-ATP6-associated disease: From isolated neuropathy to early onset neurodegeneration. Neurol Genet 2020; 6: e393 30 Lake NJ, Compton AG, Rahman S. et al. Leigh syndrome: one disorder, more than 75 monogenic causes. Ann Neurol 2016; 79: 190-203 31 Hirano M, Silvestri G, Blake DM. et al. Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): clinical, biochemical, and genetic features of an autosomal recessive mitochondrial disorder. Neurology 1994; 44: 721-727 32 Yavuz H, Ozel A, Christensen M. et al. Treatment of mitochondrial neurogastrointestinal encephalomyopathy with dialysis. Arch Neurol 2007; 64: 435-8 33 Lara MC, Weiss B, Illa I. et al. Infusion of platelets transiently reduces nucleoside overload in MNGIE. Neurology 2006; 67: 1461-3 34 Halter J, Schüpfbach WM, Mandel H. et al. Allogenic haematopoietic stem cell transplantation for mitochondrial neurogastrointestinal encephalomyopathy. Brain 2015; 138: 2847-2858 35 Halter J, Schüpfbach WM, Casali C. et al. Allogenic hematopoietic SCT as treatment option for patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): a consensus conference proposal for a standardized approach. Bone Marrow Transplant 2011; 463: 330-337 36 Bax BE, Levene M, Main MD. et al. Erythrocyte encapsulated thymidine phosphorylase for the treatment of patients with mitochondrial neurogastrointestinal encephalomyopathy: Study Protocol for a Multi-Centre, Multiple Dose, Open Label Trial. J Clin Med 2019; 8: 1096 37 DʼAngelo R, Boschetti E, Amore G. et al. Liver transplantation in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): clinical long-term follow-up and pathogenic implications. J Neurol 2020; 38 Gempel K, Topaloglu H, Talim B. et al. The myopathic form of coenzyme Q10 deficiency is caused by mutations in the electron transferring flavoprotein dehydrogenase (ETFDH) gene. Brain 2007; 130: 2017-2044 39 Swalwell H, Deschauer M, Hartl H. et al. Pure myopathy associated with a novel mitochondrial tRNA gene mutation. Neurology 2006; 66: 447-449 40 Horvath R, Hudson G, Ferrari G. et al. Phenotypic spectrum associated with mutations of the mitochondrial polymerase gamma gene. Brain 2006; 129: 1674-1684 41 Rodriguez MC, MacDonald JR, Mahoney DJ. et al. Beneficial effects of creatine, CoQ10, and lipoic acid in mitochondrial disorders. Muscle Nerv 2007; 35: 235-242 42 Gorman GS, Chinnery PF, DiMauro S. et al. Mitochondrial diseases. Nat Rev Dis Primers 2016; 2: 16080 43 Desbats MA, Lunardi G, Doimo M. et al. Genetic bases and clinical manifestations of coenzyme Q10 (CoQ 10) deficiency. J Inherit Metab Dis 2015; 38: 145-156