RSS-Feed abonnieren
Bitte kopieren Sie die angezeigte URL und fügen sie dann in Ihren RSS-Reader ein.
https://www.thieme-connect.de/rss/thieme/de/10.1055-s-00000071.xml
PDF herunterladen
Semin Neurol 2014; 34(03): 321-340
DOI: 10.1055/s-0034-1386770
DOI: 10.1055/s-0034-1386770
Mitochondrial Disorders Affecting the Nervous System
Weitere Informationen
Publikationsverlauf
Publikationsdatum:
05. September 2014 (online)
Abstract
Mitochondrial diseases are multiorgan system disorders and the brain is the most commonly affected organ. The high-energy requirement of the brain leaves it vulnerable to energy failure. All components of the neuraxis including muscle, the neuromuscular junction, peripheral nerve, spinal cord, and brain can be affected. Genetic mitochondrial disease can be caused by nuclear gene defects and mitochondrial DNA defects. Mitochondrial medicine is rapidly expanding as exome and mtDNA sequencing is identifying new gene defects on a daily basis. This review will focus on primary genetic mitochondrial diseases that impair energy production and affect the nervous system, pathophysiology of disease, classical phenotypes, diagnosis, and treatment.
-
References
- 1 Erecinska M, Cherian S, Silver IA. Energy metabolism in mammalian brain during development. Prog Neurobiol 2004; 73 (6) 397-445
- 2 HUGO Gene Nomenclature Committee. Mitochondrial respiratory chain complex. 2014. Available at: http://www.genenames.org/genefamilies/mitocomplex . Accessed June 2, 2014
- 3 Broad Institute. MitoCarta: An inventory of mammalian mitochondrial genes. 2014 . Available at: http://www.broadinstitute.org/pubs/MitoCarta/ . Accessed June 2, 2014
- 4 Wallace DC, Singh G, Lott MT , et al. Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy. Science 1988; 242 (4884) 1427-1430
- 5 Holt IJ, Cooper JM, Morgan-Hughes JA, Harding AE. Deletions of muscle mitochondrial DNA. Lancet 1988; 1 (8600) 1462
- 6 Copeland WC. Defects in mitochondrial DNA replication and human disease. Crit Rev Biochem Mol Biol 2012; 47 (1) 64-74
- 7 Stumpf JD, Saneto RP, Copeland WC. Clinical and molecular features of POLG-related mitochondrial disease. Cold Spring Harb Perspect Biol 2013; 5 (4) a011395
- 8 Chinnery PF, Elliott HR, Hudson G, Samuels DC, Relton CL. Epigenetics, epidemiology and mitochondrial DNA diseases. Int J Epidemiol 2012; 41 (1) 177-187
- 9 Schaefer AM, McFarland R, Blakely EL , et al. Prevalence of mitochondrial DNA disease in adults. Ann Neurol 2008; 63 (1) 35-39
- 10 Stewart JD, Tennant S, Powell H , et al. Novel POLG1 mutations associated with neuromuscular and liver phenotypes in adults and children. J Med Genet 2009; 46 (3) 209-214
- 11 Haas RH, Parikh S, Falk MJ , et al; Mitochondrial Medicine Society's Committee on Diagnosis. The in-depth evaluation of suspected mitochondrial disease. Mol Genet Metab 2008; 94 (1) 16-37
- 12 Alpers BJ. Diffuse progressive degeneration of the grey matter of the cerebrum. Arch Neurol Psychiatry 1931; 25: 36
- 13 Huttenlocher PR, Solitare GB, Adams G. Infantile diffuse cerebral degeneration with hepatic cirrhosis. Arch Neurol 1976; 33 (3) 186-192
- 14 Castro-Gago M, González-Conde V, Fernández-Seara MJ , et al. [Early mitochondrial encephalomyopathy due to complex IV deficiency consistent with Alpers-Huttenlocher syndrome: report of two cases]. Rev Neurol 1999; 29 (10) 912-917
- 15 Naviaux RK, Nyhan WL, Barshop BA , et al. Mitochondrial DNA polymerase gamma deficiency and mtDNA depletion in a child with Alpers' syndrome. Ann Neurol 1999; 45 (1) 54-58
- 16 Hakonen AH, Isohanni P, Paetau A, Herva R, Suomalainen A, Lönnqvist T. Recessive Twinkle mutations in early onset encephalopathy with mtDNA depletion. Brain 2007; 130 (Pt 11) 3032-3040
- 17 Elo JM, Yadavalli SS, Euro L , et al. Mitochondrial phenylalanyl-tRNA synthetase mutations underlie fatal infantile Alpers encephalopathy. Hum Mol Genet 2012; 21 (20) 4521-4529
- 18 Koene S, Rodenburg RJ, van der Knaap MS , et al. Natural disease course and genotype-phenotype correlations in Complex I deficiency caused by nuclear gene defects: what we learned from 130 cases. J Inherit Metab Dis 2012; 35 (5) 737-747
- 19 Sofou K, De Coo IF, Isohanni P , et al. A multicenter study on Leigh syndrome: disease course and predictors of survival. Orphanet J Rare Dis 2014; 9 (1) 52
- 20 Filosto M, Tomelleri G, Tonin P , et al. Neuropathology of mitochondrial diseases. Biosci Rep 2007; 27 (1-3) 23-30
- 21 Haas R, Dietrich R. Neuroimaging of mitochondrial disorders. Mitochondrion 2004; 4 (5-6) 471-490
- 22 Saneto RP, Friedman SD, Shaw DW. Neuroimaging of mitochondrial disease. Mitochondrion 2008; 8 (5-6) 396-413
- 23 Leigh D. Subacute necrotizing encephalomyelopathy in an infant. J Neurol Neurosurg Psychiatry 1951; 14 (3) 216-221
- 24 Patel KP, O'Brien TW, Subramony SH, Shuster J, Stacpoole PW. The spectrum of pyruvate dehydrogenase complex deficiency: clinical, biochemical and genetic features in 371 patients. Mol Genet Metab 2012; 106 (3) 385-394
- 25 Haas RH. Thiamin and the brain. Annu Rev Nutr 1988; 8: 483-515
- 26 Koga Y, Povalko N, Nishioka J, Katayama K, Yatsuga S, Matsuishi T. Molecular pathology of MELAS and L-arginine effects. Biochim Biophys Acta 2012; 1820 (5) 608-614
- 27 El-Hattab AW, Hsu JW, Emrick LT , et al. Restoration of impaired nitric oxide production in MELAS syndrome with citrulline and arginine supplementation. Mol Genet Metab 2012; 105 (4) 607-614
- 28 Yoneda M, Ikawa M, Arakawa K , et al. In vivo functional brain imaging and a therapeutic trial of L-arginine in MELAS patients. Biochim Biophys Acta 2012; 1820 (5) 615-618
- 29 Wang Z, Xiao J, Xie S , et al. MR evaluation of cerebral oxygen metabolism and blood flow in stroke-like episodes of MELAS. J Neurol Sci 2012; 323 (1-2) 173-177
- 30 Wong LJ. Mitochondrial syndromes with leukoencephalopathies. Semin Neurol 2012; 32 (1) 55-61
- 31 Lerman-Sagie T, Leshinsky-Silver E, Watemberg N, Luckman Y, Lev D. White matter involvement in mitochondrial diseases. Mol Genet Metab 2005; 84 (2) 127-136
- 32 Ishak GE, Poliakov AV, Poliachik SL , et al. Tract-based spatial statistical analysis of diffusion tensor imaging in pediatric patients with mitochondrial disease: widespread reduction in fractional anisotropy of white matter tracts. AJNR Am J Neuroradiol 2012; 33 (9) 1726-1730
- 33 Barkovich AJ, Good WV, Koch TK, Berg BO. Mitochondrial disorders: analysis of their clinical and imaging characteristics. AJNR Am J Neuroradiol 1993; 14 (5) 1119-1137
- 34 Giordano C, Sebastiani M, De Giorgio R , et al. Gastrointestinal dysmotility in mitochondrial neurogastrointestinal encephalomyopathy is caused by mitochondrial DNA depletion. Am J Pathol 2008; 173 (4) 1120-1128
- 35 Schuelke M, Smeitink J, Mariman E , et al. Mutant NDUFV1 subunit of mitochondrial complex I causes leukodystrophy and myoclonic epilepsy. Nat Genet 1999; 21 (3) 260-261
- 36 Ferreira M, Torraco A, Rizza T , et al. Progressive cavitating leukoencephalopathy associated with respiratory chain complex I deficiency and a novel mutation in NDUFS1. Neurogenetics 2011; 12 (1) 9-17
- 37 Brockmann K, Bjornstad A, Dechent P , et al. Succinate in dystrophic white matter: a proton magnetic resonance spectroscopy finding characteristic for complex II deficiency. Ann Neurol 2002; 52 (1) 38-46
- 38 van der Knaap MS, van der Voorn P, Barkhof F , et al. A new leukoencephalopathy with brainstem and spinal cord involvement and high lactate. Ann Neurol 2003; 53 (2) 252-258
- 39 van Berge L, Hamilton EM, Linnankivi T , et al; LBSL Research Group. Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation: clinical and genetic characterization and target for therapy. Brain 2014; 137 (Pt 4) 1019-1029
- 40 Isohanni P, Linnankivi T, Buzkova J , et al. DARS2 mutations in mitochondrial leucoencephalopathy and multiple sclerosis. J Med Genet 2010; 47 (1) 66-70
- 41 Miyake N, Yamashita S, Kurosawa K , et al. A novel homozygous mutation of DARS2 may cause a severe LBSL variant. Clin Genet 2011; 80 (3) 293-296
- 42 Dallabona C, Diodato D, Kevelam SH , et al. Novel (ovario) leukodystrophy related to AARS2 mutations. Neurology 2014; 82 (23) 2063-2071
- 43 Wong-Riley MT. Energy metabolism of the visual system. Eye Brain 2010; 2: 99-116
- 44 Yu-Wai-Man P, Griffiths PG, Gorman GS , et al. Multi-system neurological disease is common in patients with OPA1 mutations. Brain 2010; 133 (Pt 3) 771-786
- 45 Hudson G, Amati-Bonneau P, Blakely EL , et al. Mutation of OPA1 causes dominant optic atrophy with external ophthalmoplegia, ataxia, deafness and multiple mitochondrial DNA deletions: a novel disorder of mtDNA maintenance. Brain 2008; 131 (Pt 2) 329-337
- 46 Delettre C, Lenaers G, Griffoin JM , et al. Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy. Nat Genet 2000; 26 (2) 207-210
- 47 Yu-Wai-Man P, Votruba M, Moore AT, Chinnery PF. Treatment strategies for inherited optic neuropathies: past, present and future. Eye (Lond) 2014; 28 (5) 521-537
- 48 Perez F, Anne O, Debruxelles S , et al. Leber's optic neuropathy associated with disseminated white matter disease: a case report and review. Clin Neurol Neurosurg 2009; 111 (1) 83-86
- 49 Jaros E, Mahad DJ, Hudson G , et al. Primary spinal cord neurodegeneration in Leber hereditary optic neuropathy. Neurology 2007; 69 (2) 214-216
- 50 McClelland CM, Van Stavern GP, Tselis AC. Leber hereditary optic neuropathy mimicking neuromyelitis optica. J Neuroophthalmol 2011; 31 (3) 265-268
- 51 Pfeffer G, Burke A, Yu-Wai-Man P, Compston DA, Chinnery PF. Clinical features of MS associated with Leber hereditary optic neuropathy mtDNA mutations. Neurology 2013; 81 (24) 2073-2081
- 52 Cambron M, D'Haeseleer M, Laureys G, Clinckers R, Debruyne J, De Keyser J. White-matter astrocytes, axonal energy metabolism, and axonal degeneration in multiple sclerosis. J Cereb Blood Flow Metab 2012; 32 (3) 413-424
- 53 Witte ME, Mahad DJ, Lassmann H, van Horssen J. Mitochondrial dysfunction contributes to neurodegeneration in multiple sclerosis. Trends Mol Med 2014; 20 (3) 179-187
- 54 Naviaux RK. Metabolic features of the cell danger response. Mitochondrion 2014; 16: 7-17
- 55 Su K, Bourdette D, Forte M. Mitochondrial dysfunction and neurodegeneration in multiple sclerosis. Front Physiol 2013; 4: 169
- 56 Pareyson D, Piscosquito G, Moroni I, Salsano E, Zeviani M. Peripheral neuropathy in mitochondrial disorders. Lancet Neurol 2013; 12 (10) 1011-1024
- 57 Milone M, Klassen BT, Landsverk ML, Haas RH, Wong LJ. Orthostatic tremor, progressive external ophthalmoplegia, and Twinkle. JAMA Neurol 2013; 70 (11) 1429-1431
- 58 Blakely EL, Butterworth A, Hadden RD , et al. MPV17 mutation causes neuropathy and leukoencephalopathy with multiple mtDNA deletions in muscle. Neuromuscul Disord 2012; 22 (7) 587-591
- 59 Karadimas CL, Vu TH, Holve SA , et al. Navajo neurohepatopathy is caused by a mutation in the MPV17 gene. Am J Hum Genet 2006; 79 (3) 544-548
- 60 van den Ouweland JM, Lemkes HH, Trembath RC , et al. Maternally inherited diabetes and deafness is a distinct subtype of diabetes and associates with a single point mutation in the mitochondrial tRNA(Leu(UUR)) gene. Diabetes 1994; 43 (6) 746-751
- 61 Klein CJ, Kimmel GW, Pittock SJ , et al. Large kindred evaluation of mitofusin 2 novel mutation, extremes of neurologic presentations, and preserved nerve mitochondria. Arch Neurol 2011; 68 (10) 1295-1302
- 62 Cohen BH. Neuromuscular and systemic presentations in adults: diagnoses beyond MERRF and MELAS. Neurotherapeutics 2013; 10 (2) 227-242
- 63 Martignago S, Fanin M, Albertini E, Pegoraro E, Angelini C. Muscle histopathology in myasthenia gravis with antibodies against MuSK and AChR. Neuropathol Appl Neurobiol 2009; 35 (1) 103-110
- 64 Barton JJ, Maguire J, Mezei M, Hurwitz T, Briemberg HR. Mitochondrial pseudomyasthenia. J Neuroophthalmol 2010; 30 (3) 248-251
- 65 Behbehani R, Sharfuddin K, Anim JT. Mitochondrial ophthalmoplegia with fatigable weakness and elevated acetylcholine receptor antibody. J Neuroophthalmol 2007; 27 (1) 41-44
- 66 Plewnia K, Dotti MT, Malandrini A , et al. A rare association of myasthenia gravis and mitochondrial myopathy: a clinical, biochemical and morphologic study of one case. J Submicrosc Cytol Pathol 1997; 29 (3) 335-338
- 67 Gonzalez-Moron D, Bueri J, Kauffman MA. Progressive external ophthalmoplegia (PEO) due to a mutation in the C10orf2 (PEO1) gene mimicking a myasthenic crisis. BMJ Case Rep 2013; 2013
- 68 Ben Yaou R, Laforêt P, Bécane HM , et al. [Misdiagnosis of mitochondrial myopathies: a study of 12 thymectomized patients]. Rev Neurol (Paris) 2006; 162 (3) 339-346
- 69 Milone M, Wong LJ. Diagnosis of mitochondrial myopathies. Mol Genet Metab 2013; 110 (1-2) 35-41
- 70 Pfeffer G, Chinnery PF. Diagnosis and treatment of mitochondrial myopathies. Ann Med 2013; 45 (1) 4-16
- 71 Tarnopolsky MA, Raha S. Mitochondrial myopathies: diagnosis, exercise intolerance, and treatment options. Med Sci Sports Exerc 2005; 37 (12) 2086-2093
- 72 Gorman GS, Taylor RW. Mitochondrial DNA abnormalities in ophthalmological disease. Saudi J Ophthalmol 2011; 25 (4) 395-404
- 73 Mayr R. Structure and distribution of fibre types in the external eye muscles of the rat. Tissue Cell 1971; 3 (3) 433-462
- 74 Yu-Wai-Man P, Lai-Cheong J, Borthwick GM , et al. Somatic mitochondrial DNA deletions accumulate to high levels in aging human extraocular muscles. Invest Ophthalmol Vis Sci 2010; 51 (7) 3347-3353
- 75 Scaglia F, Towbin JA, Craigen WJ , et al. Clinical spectrum, morbidity, and mortality in 113 pediatric patients with mitochondrial disease. Pediatrics 2004; 114 (4) 925-931
- 76 Hom XB, Lavine JE. Gastrointestinal complications of mitochondrial disease. Mitochondrion 2004; 4 (5-6) 601-607
- 77 Sekino Y, Inamori M, Yamada E , et al. Characteristics of intestinal pseudo-obstruction in patients with mitochondrial diseases. World J Gastroenterol 2012; 18 (33) 4557-4562
- 78 Blondon H, Polivka M, Joly F, Flourie B, Mikol J, Messing B. Digestive smooth muscle mitochondrial myopathy in patients with mitochondrial-neuro-gastro-intestinal encephalomyopathy (MNGIE). Gastroenterol Clin Biol 2005; 29 (8-9) 773-778
- 79 Baertling F, Rodenburg RJ, Schaper J , et al. A guide to diagnosis and treatment of Leigh syndrome. J Neurol Neurosurg Psychiatry 2014; 85 (3) 257-265
- 80 Finsterer J. Leigh and Leigh-like syndrome in children and adults. Pediatr Neurol 2008; 39 (4) 223-235
- 81 Lim SC, Smith KR, Stroud DA , et al. A founder mutation in PET100 causes isolated complex IV deficiency in Lebanese individuals with Leigh syndrome. Am J Hum Genet 2014; 94 (2) 209-222
- 82 Levy RJ, Ríos PG, Akman HO, Sciacco M, Vivo DC, Dimauro S. Long survival in patients with Leigh syndrome and the m.10191T>C mutation in MT-ND3: a case report and review of the literature. J Child Neurol 2013; (Nov) 27
- 83 Jin T, Shen H, Zhao Z, Hu J. Clinical, pathological, and neuroimaging analyses of two cases of Leigh syndrome in a Chinese family. J Child Neurol 2014; (Jan) 10
- 84 Nesbitt V, Morrison PJ, Crushell E , et al. The clinical spectrum of the m.10191T>C mutation in complex I-deficient Leigh syndrome. Dev Med Child Neurol 2012; 54 (6) 500-506
- 85 Atwal PS. Mutations in the Complex III assembly factor tetratricopeptide 19 gene TTC19 are a rare cause of Leigh syndrome. JIMD Rep 2013;
- 86 Ji K, Zheng J, Sun B , et al. Novel mitochondrial C15620A variant may modulate the phenotype of mitochondrial G11778A mutation in a Chinese family with Leigh syndrome. Neuromolecular Med 2014; 16 (1) 119-126
- 87 Ma YY, Wu TF, Liu YP , et al. Genetic and biochemical findings in Chinese children with Leigh syndrome. J Clin Neurosci 2013; 20 (11) 1591-1594
- 88 Tarnopolsky M, Meaney B, Robinson B, Sheldon K, Boles RG. Severe infantile Leigh syndrome associated with a rare mitochondrial ND6 mutation, m.14487T>C. Am J Med Genet A 2013; 161A (8) 2020-2023
- 89 Quinonez SC, Leber SM, Martin DM, Thoene JG, Bedoyan JK. Leigh syndrome in a girl with a novel DLD mutation causing E3 deficiency. Pediatr Neurol 2013; 48 (1) 67-72
- 90 Marin SE, Mesterman R, Robinson B, Rodenburg RJ, Smeitink J, Tarnopolsky MA. Leigh syndrome associated with mitochondrial complex I deficiency due to novel mutations In NDUFV1 and NDUFS2. Gene 2013; 516 (1) 162-167
- 91 Monlleo-Neila L, Toro MD, Bornstein B , et al. Leigh syndrome and the mitochondrial m.13513G>A mutation: expanding the clinical spectrum. J Child Neurol 2013; 28 (11) 1531-1534
- 92 Lee IC, El-Hattab AW, Wang J , et al. SURF1-associated Leigh syndrome: a case series and novel mutations. Hum Mutat 2012; 33 (8) 1192-1200
- 93 Tanigawa J, Kaneko K, Honda M , et al. Two Japanese patients with Leigh syndrome caused by novel SURF1 mutations. Brain Dev 2012; 34 (10) 861-865
- 94 Cox R, Platt J, Chen LC, Tang S, Wong LJ, Enns GM. Leigh syndrome caused by a novel m.4296G>A mutation in mitochondrial tRNA isoleucine. Mitochondrion 2012; 12 (2) 258-261
- 95 Wedatilake Y, Brown R, McFarland R , et al. SURF1 deficiency: a multi-centre natural history study. Orphanet J Rare Dis 2013; 8 (1) 96
- 96 Leshinsky-Silver E, Lev D, Malinger G , et al. Leigh disease presenting in utero due to a novel missense mutation in the mitochondrial DNA-ND3. Mol Genet Metab 2010; 100 (1) 65-70
- 97 Buda P, Piekutowska-Abramczuk D, Karkucińska-Więckowska A , et al. “Drop attacks” as first clinical symptoms in a child carrying MTTK m.8344A>G mutation. Folia Neuropathol 2013; 51 (4) 347-354
- 98 McKelvie P, Infeld B, Marotta R, Chin J, Thorburn D, Collins S. Late-adult onset Leigh syndrome. J Clin Neurosci 2012; 19 (2) 195-202
- 99 Thorburn DR, Rahman S. Mitochondrial DNA-associated Leigh syndrome and NARP. In: Pagon RA, Adam MP, Ardinger HH, , et al., eds. GeneReviews® [Internet]. Seattle, WA: University of Washington, Seattle; 1993-2014
- 100 Rahman S, Blok RB, Dahl HH , et al. Leigh syndrome: clinical features and biochemical and DNA abnormalities. Ann Neurol 1996; 39 (3) 343-351
- 101 Ozand PT, Gascon GG, Al Essa M , et al. Biotin-responsive basal ganglia disease: a novel entity. Brain 1998; 121 (Pt 7) 1267-1279
- 102 Zeng WQ, Al-Yamani E, Acierno Jr JS , et al. Biotin-responsive basal ganglia disease maps to 2q36.3 and is due to mutations in SLC19A3. Am J Hum Genet 2005; 77 (1) 16-26
- 103 Alfadhel M, Almuntashri M, Jadah RH , et al. Biotin-responsive basal ganglia disease should be renamed biotin-thiamine-responsive basal ganglia disease: a retrospective review of the clinical, radiological and molecular findings of 18 new cases. Orphanet J Rare Dis 2013; 8: 83
- 104 Mitchell G, Ogier H, Munnich A , et al. Neurological deterioration and lactic acidemia in biotinidase deficiency. A treatable condition mimicking Leigh's disease. Neuropediatrics 1986; 17 (3) 129-131
- 105 Baumgartner ER, Suormala TM, Wick H , et al. Biotinidase deficiency: a cause of subacute necrotizing encephalomyelopathy (Leigh syndrome). Report of a case with lethal outcome. Pediatr Res 1989; 26 (3) 260-266
- 106 Dhar SU, Scaglia F, Li FY , et al. Expanded clinical and molecular spectrum of guanidinoacetate methyltransferase (GAMT) deficiency. Mol Genet Metab 2009; 96 (1) 38-43
- 107 Morris AA, Appleton RE, Power B , et al. Guanidinoacetate methyltransferase deficiency masquerading as a mitochondrial encephalopathy. J Inherit Metab Dis 2007; 30 (1) 100
- 108 Hathaway SC, Friez M, Limbo K , et al. X-linked creatine transporter deficiency presenting as a mitochondrial disorder. J Child Neurol 2010; 25 (8) 1009-1012
- 109 Longo N, Ardon O, Vanzo R, Schwartz E, Pasquali M. Disorders of creatine transport and metabolism. Am J Med Genet C Semin Med Genet 2011; 157C (1) 72-78
- 110 Koopman WJ, Distelmaier F, Smeitink JA, Willems PH. OXPHOS mutations and neurodegeneration. EMBO J 2013; 32 (1) 9-29
- 111 Chinnery PF. Mitochondrial Disorders Overview. In: Pagon RA, Adam MP, Ardinger HH, , et al., eds. GeneReviews® [Internet]. Seattle, WA: University of Washington, Seattle; 1993-2014
- 112 Holt IJ, Harding AE, Petty RK, Morgan-Hughes JA. A new mitochondrial disease associated with mitochondrial DNA heteroplasmy. Am J Hum Genet 1990; 46 (3) 428-433
- 113 Gelfand JM, Duncan JL, Racine CA , et al. Heterogeneous patterns of tissue injury in NARP syndrome. J Neurol 2011; 258 (3) 440-448
- 114 Taylor RW, Turnbull DM. Mitochondrial DNA mutations in human disease. Nat Rev Genet 2005; 6 (5) 389-402
- 115 White SL, Collins VR, Wolfe R , et al. Genetic counseling and prenatal diagnosis for the mitochondrial DNA mutations at nucleotide 8993. Am J Hum Genet 1999; 65 (2) 474-482
- 116 Uziel G, Moroni I, Lamantea E , et al. Mitochondrial disease associated with the T8993G mutation of the mitochondrial ATPase 6 gene: a clinical, biochemical, and molecular study in six families. J Neurol Neurosurg Psychiatry 1997; 63 (1) 16-22
- 117 Harvey JN, Barnett D. Endocrine dysfunction in Kearns-Sayre syndrome. Clin Endocrinol (Oxf) 1992; 37 (1) 97-103
- 118 Chawla S, Coku J, Forbes T, Kannan S. Kearns-Sayre syndrome presenting as complete heart block. Pediatr Cardiol 2008; 29 (3) 659-662
- 119 Michels AW, Gottlieb PA. Autoimmune polyglandular syndromes. Nat Rev Endocrinol 2010; 6 (5) 270-277
- 120 Tzoufi M, Makis A, Chaliasos N , et al. A rare case report of simultaneous presentation of myopathy, Addison's disease, primary hypoparathyroidism, and Fanconi syndrome in a child diagnosed with Kearns-Sayre syndrome. Eur J Pediatr 2013; 172 (4) 557-561
- 121 DiMauro S, Hirano M. Mitochondrial DNA Deletion Syndromes. In: Pagon RA, Adam MP, Ardinger HH, , et al., eds. GeneReviews® [Internet]. Seattle, WA: University of Washington, Seattle; 1993-2014
- 122 Grady JP, Campbell G, Ratnaike T , et al. Disease progression in patients with single, large-scale mitochondrial DNA deletions. Brain 2014; 137 (Pt 2) 323-334
- 123 Harding AE, Hammans SR. Deletions of the mitochondrial genome. J Inherit Metab Dis 1992; 15 (4) 480-486
- 124 Moraes CT, DiMauro S, Zeviani M , et al. Mitochondrial DNA deletions in progressive external ophthalmoplegia and Kearns-Sayre syndrome. N Engl J Med 1989; 320 (20) 1293-1299
- 125 Larsson NG, Holme E, Kristiansson B, Oldfors A, Tulinius M. Progressive increase of the mutated mitochondrial DNA fraction in Kearns-Sayre syndrome. Pediatr Res 1990; 28 (2) 131-136
- 126 Rahman S, Leonard JV. Early onset of complete heart block in Pearson syndrome. J Inherit Metab Dis 2000; 23 (7) 753-754
- 127 Bau V, Zierz S. Update on chronic progressive external ophthalmoplegia. Strabismus 2005; 13 (3) 133-142
- 128 Pfeffer G, Sirrs S, Wade NK, Mezei MM. Multisystem disorder in late-onset chronic progressive external ophthalmoplegia. Can J Neurol Sci 2011; 38 (1) 119-123
- 129 Fraser JA, Biousse V, Newman NJ. The neuro-ophthalmology of mitochondrial disease. Surv Ophthalmol 2010; 55 (4) 299-334
- 130 Tyynismaa H, Ylikallio E, Patel M, Molnar MJ, Haller RG, Suomalainen A. A heterozygous truncating mutation in RRM2B causes autosomal-dominant progressive external ophthalmoplegia with multiple mtDNA deletions. Am J Hum Genet 2009; 85 (2) 290-295
- 131 Fratter C, Raman P, Alston CL , et al. RRM2B mutations are frequent in familial PEO with multiple mtDNA deletions. Neurology 2011; 76 (23) 2032-2034
- 132 Pfeffer G, Gorman GS, Griffin H , et al. Mutations in the SPG7 gene cause chronic progressive external ophthalmoplegia through disordered mitochondrial DNA maintenance. Brain 2014; 137 (Pt 5) 1323-1336
- 133 Ciafaloni E, Ricci E, Shanske S , et al. MELAS: clinical features, biochemistry, and molecular genetics. Ann Neurol 1992; 31 (4) 391-398
- 134 Hirano M, Pavlakis SG. Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS): current concepts. J Child Neurol 1994; 9 (1) 4-13
- 135 DiMauro S, Hirano M. MELAS. In: Pagon RA, Adam MP, Ardinger HH, , et al., eds. GeneReviews® [Internet]. Seattle, WA: University of Washington, Seattle; 1993-2014
- 136 Kaufmann P, Engelstad K, Wei Y , et al. Natural history of MELAS associated with mitochondrial DNA m.3243A>G genotype. Neurology 2011; 77 (22) 1965-1971
- 137 Hirano M, Ricci E, Koenigsberger MR , et al. Melas: an original case and clinical criteria for diagnosis. Neuromuscul Disord 1992; 2 (2) 125-135
- 138 Goto Y, Nonaka I, Horai S. A mutation in the tRNA(Leu)(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies. Nature 1990; 348 (6302) 651-653
- 139 Nesbitt V, Pitceathly RD, Turnbull DM , et al. The UK MRC Mitochondrial Disease Patient Cohort Study: clinical phenotypes associated with the m.3243A>G mutation—implications for diagnosis and management. J Neurol Neurosurg Psychiatry 2013; 84 (8) 936-938
- 140 Mehrazin M, Shanske S, Kaufmann P , et al. Longitudinal changes of mtDNA A3243G mutation load and level of functioning in MELAS. Am J Med Genet A 2009; 149A (4) 584-587
- 141 Kaufmann P, Engelstad K, Wei Y , et al. Protean phenotypic features of the A3243G mitochondrial DNA mutation. Arch Neurol 2009; 66 (1) 85-91
- 142 Dinopoulos A, Cecil KM, Schapiro MB , et al. Brain MRI and proton MRS findings in infants and children with respiratory chain defects. Neuropediatrics 2005; 36 (5) 290-301
- 143 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 (6) 601-605
- 144 Fukuhara N, Tokiguchi S, Shirakawa K, Tsubaki T. Myoclonus epilepsy associated with ragged-red fibres (mitochondrial abnormalities ): disease entity or a syndrome? Light-and electron-microscopic studies of two cases and review of literature. J Neurol Sci 1980; 47 (1) 117-133
- 145 DiMauro S, Hirano M. MERRF. In: Pagon RA, Adam MP, Ardinger HH, , et al., eds. GeneReviews® [Internet]. Seattle, WA: University of Washington, Seattle; 1993-2014
- 146 Noer AS, Sudoyo H, Lertrit P , et al. A tRNA(Lys) mutation in the mtDNA is the causal genetic lesion underlying myoclonic epilepsy and ragged-red fiber (MERRF) syndrome. Am J Hum Genet 1991; 49 (4) 715-722
- 147 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 (6) 1200-1206
- 148 Mancuso M, Orsucci D, Angelini C , et al. Phenotypic heterogeneity of the 8344A>G mtDNA “MERRF” mutation. Neurology 2013; 80 (22) 2049-2054
- 149 Chinnery PF, Howell N, Lightowlers RN, Turnbull DM. Molecular pathology of MELAS and MERRF. The relationship between mutation load and clinical phenotypes. Brain 1997; 120 (Pt 10) 1713-1721
- 150 Yu-Wai-Man P, Griffiths PG, Chinnery PF. Mitochondrial optic neuropathies - disease mechanisms and therapeutic strategies. Prog Retin Eye Res 2011; 30 (2) 81-114
- 151 Carelli V, La Morgia C, Valentino ML, Barboni P, Ross-Cisneros FN, Sadun AA. Retinal ganglion cell neurodegeneration in mitochondrial inherited disorders. Biochim Biophys Acta 2009; 1787 (5) 518-528
- 152 Lüdtke H, Kriegbaum C, Leo-Kottler B, Wilhelm H. Pupillary light reflexes in patients with Leber's hereditary optic neuropathy. Graefes Arch Clin Exp Ophthalmol 1999; 237 (3) 207-211
- 153 Bose S, Dhillon N, Ross-Cisneros FN, Carelli V. Relative post-mortem sparing of afferent pupil fibers in a patient with 3460 Leber's hereditary optic neuropathy. Graefes Arch Clin Exp Ophthalmol 2005; 243 (11) 1175-1179
- 154 Nikoskelainen E, Hoyt WF, Nummelin K. Ophthalmoscopic findings in Leber's hereditary optic neuropathy. I. Fundus findings in asymptomatic family members. Arch Ophthalmol 1982; 100 (10) 1597-1602
- 155 Carelli V, La Morgia C, Sadun AA. Mitochondrial dysfunction in optic neuropathies: animal models and therapeutic options. Curr Opin Neurol 2013; 26 (1) 52-58
- 156 Maresca A, la Morgia C, Caporali L, Valentino ML, Carelli V. The optic nerve: a “mito-window” on mitochondrial neurodegeneration. Mol Cell Neurosci 2013; 55: 62-76
- 157 Valentino ML, Barboni P, Ghelli A , et al. The ND1 gene of complex I is a mutational hot spot for Leber's hereditary optic neuropathy. Ann Neurol 2004; 56 (5) 631-641
- 158 Chinnery PF, Brown DT, Andrews RM , et al. The mitochondrial ND6 gene is a hot spot for mutations that cause Leber's hereditary optic neuropathy. Brain 2001; 124 (Pt 1) 209-218
- 159 Carelli V, Achilli A, Valentino ML , et al. Haplogroup effects and recombination of mitochondrial DNA: novel clues from the analysis of Leber hereditary optic neuropathy pedigrees. Am J Hum Genet 2006; 78 (4) 564-574
- 160 Carelli V, La Morgia C, Iommarini L , et al. Mitochondrial optic neuropathies: how two genomes may kill the same cell type?. Biosci Rep 2007; 27 (1-3) 173-184
- 161 Yu-Wai-Man P, Griffiths PG, Hudson G, Chinnery PF. Inherited mitochondrial optic neuropathies. J Med Genet 2009; 46 (3) 145-158
- 162 Hudson G, Carelli V, Spruijt L , et al. Clinical expression of Leber hereditary optic neuropathy is affected by the mitochondrial DNA-haplogroup background. Am J Hum Genet 2007; 81 (2) 228-233
- 163 El-Hattab AW, Scaglia F. Mitochondrial DNA depletion syndromes: review and updates of genetic basis, manifestations, and therapeutic options. Neurotherapeutics 2013; 10 (2) 186-198
- 164 Suomalainen A, Isohanni P. Mitochondrial DNA depletion syndromes—many genes, common mechanisms. Neuromuscul Disord 2010; 20 (7) 429-437
- 165 Spinazzola A, Invernizzi F, Carrara F , et al. Clinical and molecular features of mitochondrial DNA depletion syndromes. J Inherit Metab Dis 2009; 32 (2) 143-158
- 166 Finsterer J, Ahting U. Mitochondrial depletion syndromes in children and adults. Can J Neurol Sci 2013; 40 (5) 635-644
- 167 Gorman GS, Taylor RW. RRM2B-Related Mitochondrial Disease. In: Pagon RA, Adam MP, Ardinger HH, , et al., eds. GeneReviews® [Internet]. Seattle, WA: University of Washington, Seattle; 1993-2014
- 168 Shaibani A, Shchelochkov OA, Zhang S , et al. Mitochondrial neurogastrointestinal encephalopathy due to mutations in RRM2B. Arch Neurol 2009; 66 (8) 1028-1032
- 169 Pitceathly RD, Smith C, Fratter C , et al. Adults with RRM2B-related mitochondrial disease have distinct clinical and molecular characteristics. Brain 2012; 135 (Pt 11) 3392-3403
- 170 Scaglia F, Dimmock D, Wong LJ. DGUOK-Related Mitochondrial DNA Depletion Syndrome, Hepatocerebral Form. In: Pagon RA, Adam MP, Ardinger HH, , et al., eds. GeneReviews® [Internet]. Seattle, WA: University of Washington, Seattle; 1993-2014
- 171 Brahimi N, Jambou M, Sarzi E , et al. The first founder DGUOK mutation associated with hepatocerebral mitochondrial DNA depletion syndrome. Mol Genet Metab 2009; 97 (3) 221-226
- 172 Naviaux RK, Nguyen KV. POLG mutations associated with Alpers' syndrome and mitochondrial DNA depletion. Ann Neurol 2004; 55 (5) 706-712
- 173 Cohen BH, Naviaux RK. The clinical diagnosis of POLG disease and other mitochondrial DNA depletion disorders. Methods 2010; 51 (4) 364-373
- 174 Saneto RP, Lee IC, Koenig MK , et al. POLG DNA testing as an emerging standard of care before instituting valproic acid therapy for pediatric seizure disorders. Seizure 2010; 19 (3) 140-146
- 175 Okamura K, Santa T, Nagae K, Omae T. Congenital oculoskeletal myopathy with abnormal muscle and liver mitochondria. J Neurol Sci 1976; 27 (1) 79-91
- 176 Nishino I, Spinazzola A, Hirano M. Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder. Science 1999; 283 (5402) 689-692
- 177 Spinazzola A, Marti R, Nishino I , et al. Altered thymidine metabolism due to defects of thymidine phosphorylase. J Biol Chem 2002; 277 (6) 4128-4133
- 178 Martí R, Nishigaki Y, Hirano M. Elevated plasma deoxyuridine in patients with thymidine phosphorylase deficiency. Biochem Biophys Res Commun 2003; 303 (1) 14-18
- 179 Valentino ML, Martí R, Tadesse S , et al. Thymidine and deoxyuridine accumulate in tissues of patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). FEBS Lett 2007; 581 (18) 3410-3414
- 180 Garone C, Tadesse S, Hirano M. Clinical and genetic spectrum of mitochondrial neurogastrointestinal encephalomyopathy. Brain 2011; 134 (Pt 11) 3326-3332
- 181 Hirano M, Garone C, Quinzii CM. CoQ(10) deficiencies and MNGIE: two treatable mitochondrial disorders. Biochim Biophys Acta 2012; 1820 (5) 625-631
- 182 Miles MV, Miles L, Tang PH , et al. Systematic evaluation of muscle coenzyme Q10 content in children with mitochondrial respiratory chain enzyme deficiencies. Mitochondrion 2008; 8 (2) 170-180
- 183 Ashraf S, Gee HY, Woerner S , et al. ADCK4 mutations promote steroid-resistant nephrotic syndrome through CoQ10 biosynthesis disruption. J Clin Invest 2013; 123 (12) 5179-5189
- 184 Quinzii CM, Hirano M. Coenzyme Q and mitochondrial disease. Dev Disabil Res Rev 2010; 16 (2) 183-188
- 185 Cooper JM, Korlipara LV, Hart PE, Bradley JL, Schapira AH. Coenzyme Q10 and vitamin E deficiency in Friedreich's ataxia: predictor of efficacy of vitamin E and coenzyme Q10 therapy. Eur J Neurol 2008; 15 (12) 1371-1379
- 186 Montero R, Grazina M, López-Gallardo E , et al; Coenzyme Q10 Deficiency Study Group. Coenzyme Q10 deficiency in mitochondrial DNA depletion syndromes. Mitochondrion 2013; 13 (4) 337-341
- 187 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 (Pt 8) 2037-2044
- 188 Wolf NI, Smeitink JA. Mitochondrial disorders: a proposal for consensus diagnostic criteria in infants and children. Neurology 2002; 59 (9) 1402-1405
- 189 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 (9) 1406-1411
- 190 Haas RH, Parikh S, Falk MJ , et al. Mitochondrial disease: a practical approach for primary care physicians. Pediatrics 2007; 120 (6) 1326-1333
- 191 Dimauro S, Davidzon G. Mitochondrial DNA and disease. Ann Med 2005; 37 (3) 222-232
- 192 Gai X, Ghezzi D, Johnson MA , et al. Mutations in FBXL4, encoding a mitochondrial protein, cause early-onset mitochondrial encephalomyopathy. Am J Hum Genet 2013; 93 (3) 482-495
- 193 Nouws J, Wibrand F, van den Brand M , et al. A patient with Complex I deficiency caused by a novel ACAD9 mutation not responding to riboflavin treatment. JIMD Rep 2014; 12: 37-45
- 194 Parikh S, Saneto R, Falk MJ , et al. A modern approach to the treatment of mitochondrial disease. Curr Treat Options Neurol 2009; 11 (6) 414-430
- 195 Avula S, Parikh S, Demarest S, Kurz J, Gropman A. Treatment of mitochondrial disorders.
Curr Treat Options Neurol 2014; 16 (6) 292
MissingFormLabel
- 196 Glover EI, Martin J, Maher A, Thornhill RE, Moran GR, Tarnopolsky MA. A randomized trial of coenzyme Q10 in mitochondrial disorders. Muscle Nerve 2010; 42 (5) 739-748
- 197 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 (2) 235-242
- 198 Cejudo P, Bautista J, Montemayor T , et al. Exercise training in mitochondrial myopathy: a randomized controlled trial. Muscle Nerve 2005; 32 (3) 342-350
- 199 Taivassalo T, Gardner JL, Taylor RW , et al. Endurance training and detraining in mitochondrial myopathies due to single large-scale mtDNA deletions. Brain 2006; 129 (Pt 12) 3391-3401
- 200 Jeppesen TD, Schwartz M, Olsen DB , et al. Aerobic training is safe and improves exercise capacity in patients with mitochondrial myopathy. Brain 2006; 129 (Pt 12) 3402-3412
- 201 Abdelmalak M, Lew A, Ramezani R , et al. Long-term safety of dichloroacetate in congenital lactic acidosis. Mol Genet Metab 2013; 109 (2) 139-143
- 202 Stacpoole PW, Kurtz TL, Han Z, Langaee T. Role of dichloroacetate in the treatment of genetic mitochondrial diseases. Adv Drug Deliv Rev 2008; 60 (13-14) 1478-1487
- 203 Martinelli D, Catteruccia M, Piemonte F , et al. EPI-743 reverses the progression of the pediatric mitochondrial disease—genetically defined Leigh syndrome. Mol Genet Metab 2012; 107 (3) 383-388