Leigh syndrome: One disorder, more than 75 monogenic causes

Annals of Neurology

Volumn 79, Issue 2, 2016, Pages 190-203

  Lake, Nicole J ^a,b   Compton, Alison G ^a,b   Rahman, Shamima ^c   Thorburn, David R ^a,b,d  

^a MURDOCH CHILDREN'S RESEARCH INSTITUTE   (Australia)

^b UNIVERSITY OF MELBOURNE   (Australia)

^c UNIVERSITY COLLEGE LONDON   (United Kingdom)

^d ROYAL CHILDREN'S HOSPITAL   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIOXIDANT; CYTOCHROME C OXIDASE; MITOCHONDRIAL DNA; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE INHIBITOR; NICOTINAMIDE RIBOSIDE; PYRUVATE DEHYDROGENASE COMPLEX; RAPAMYCIN; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE DEHYDROGENASE (UBIQUINONE); RP 103; SUCCINATE DEHYDROGENASE (UBIQUINONE); UBIDECARENONE; UBIQUINOL CYTOCHROME C REDUCTASE; UNCLASSIFIED DRUG; VATIQUINONE;

BLOOD CHEMISTRY; CLINICAL FEATURE; COENZYME Q10 DEFICIENCY; COMPLEX I DEFICIENCY; COMPLEX II DEFICIENCY; COMPLEX III DEFICIENCY; CYTOCHROME C OXIDASE DEFICIENCY; GENE MUTATION; GENETIC ASSOCIATION; GENOTYPE PHENOTYPE CORRELATION; HEREDITY; HUMAN; LEIGH DISEASE; MELAS SYNDROME; METABOLISM; MITOCHONDRIAL ENCEPHALOPATHY; MOLECULAR GENETICS; NERVE DEGENERATION; NEUROPATHOLOGY; NEURORADIOLOGY; NONHUMAN; ONSET AGE; OXIDATIVE PHOSPHORYLATION; OXIDATIVE STRESS; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN METABOLISM; PYRUVATE DEHYDROGENASE COMPLEX DEFICIENCY; REVIEW; RISK FACTOR; ANIMAL; GENETICS; PATHOLOGY; PATHOPHYSIOLOGY;

ANIMALS; HUMANS; LEIGH DISEASE;

EID: 84958104737     PISSN: 03645134     EISSN: 15318249     Source Type: Journal    
DOI: 10.1002/ana.24551     Document Type: Review

References (116)

1. Skladal D, Halliday J, Thorburn DR,. Minimum birth prevalence of mitochondrial respiratory chain disorders in children. Brain 2003; 126: 1905-1912.
2. Rahman S, Blok RB, Dahl HH, et al., Leigh syndrome: clinical features and biochemical and DNA abnormalities. Ann Neurol 1996; 39: 343-351.
3. Morin C, Mitchell G, Larochelle J, et al., Clinical, metabolic, and genetic aspects of cytochrome C oxidase deficiency in Saguenay-Lac-Saint-Jean. Am J Hum Genet 1993; 53: 488-496.
4. Ostergaard E, Hansen FJ, Sorensen N, et al., Mitochondrial encephalomyopathy with elevated methylmalonic acid is caused by SUCLA2 mutations. Brain 2007; 130: 853-861.
5. Hammans SR, Sweeney MG, Brockington M, et al., Mitochondrial encephalopathies: molecular genetic diagnosis from blood samples. Lancet 1991; 337: 1311-1313.
6. 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: 52.
7. Ma YY, Wu TF, Liu YP, et al., Genetic and biochemical findings in Chinese children with Leigh syndrome. J Clin Neurosci 2013; 20: 1591-1594.
8. van Erven PM, Cillessen JP, Eekhoff EM, et al., Leigh syndrome, a mitochondrial encephalo(myo)pathy. A review of the literature. Clin Neurol Neurosurg 1987; 89: 217-230.
9. Lopez LC, Schuelke M, Quinzii CM, et al., Leigh syndrome with nephropathy and CoQ10 deficiency due to decaprenyl diphosphate synthase subunit 2 (PDSS2) mutations. Am J Hum Genet 2006; 79: 1125-1129.
10. Langes K, Frenzel H, Seitz R, et al., Cardiomyopathy associated with Leigh's disease. Virchows Arch A Pathol Anat Histopathol 1985; 407: 97-105.
11. 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: 1531-1534.
12. Broide E, Elpeleg O, Lahat E,. Type IV 3-methylglutaconic (3-MGC) aciduria: a new case presenting with hepatic dysfunction. Pediatr Neurol 1997; 17: 353-355.
13. Montpetit VJ, Andermann F, Carpenter S, et al., Subacute necrotizing encephalomyelopathy. A review and a study of two families. Brain 1971; 94: 1-30.
14. McKelvie P, Infeld B, Marotta R, et al., Late-adult onset Leigh syndrome. J Clin Neurosci 2012; 19: 195-202.
15. Cavanagh JB, Harding BN,. Pathogenic factors underlying the lesions in Leigh's disease. Tissue responses to cellular energy deprivation and their clinico-pathological consequences. Brain 1994; 117 (pt 6): 1357-1376.
16. Lake NJ, Bird MJ, Isohanni P, et al., Leigh syndrome: neuropathology and pathogenesis. J Neuropathol Exp Neurol 2015; 74: 482-492.
17. Arii J, Tanabe Y,. Leigh syndrome: serial MR imaging and clinical follow-up. AJNR Am J Neuroradiol 2000; 21: 1502-1509.
18. Leigh D,. Subacute necrotizing encephalomyelopathy in an infant. J Neurol Neurosurg Psychiatry 1951; 14: 216-221.
19. Baertling F, Rodenburg RJ, Schaper J, et al., A guide to diagnosis and treatment of Leigh syndrome. J Neurol Neurosurg Psychiatry 2014; 85: 257-265.
20. Worsley HE, Brookfield RW, Elwood JS, et al., Lactic acidosis with necrotizing encephalopathy in two sibs. Arch Dis Child 1965; 40: 492-501.
21. Farmer T, Veath L, Miller A, et al., Pyruvate decarboxylase deficiency in a patient with subacute necrotizing encephalomyelopathy. Neurology 1973; 23: 429.
22. Willems JL, Monnens LA, Trijbels JM, et al., Leigh's encephalomyelopathy in a patient with cytochrome c oxidase deficiency in muscle tissue. Pediatrics 1977; 60: 850-857.
23. Van Erven PM, Gabreels FJ, Ruitenbeek W, et al., Subacute necrotizing encephalomyelopathy (Leigh syndrome) associated with disturbed oxidation of pyruvate, malate and 2-oxoglutarate in muscle and liver. Acta Neurol Scand 1985; 72: 36-42.
24. Fassone E, Rahman S,. Complex I deficiency: clinical features, biochemistry and molecular genetics. J Med Genet 2012; 49: 578-590.
25. Assouline Z, Jambou M, Rio M, et al., A constant and similar assembly defect of mitochondrial respiratory chain complex I allows rapid identification of NDUFS4 mutations in patients with Leigh syndrome. Biochim Biophys Acta 2012; 1822: 1062-1069.
26. Marin SE, Mesterman R, Robinson B, et al., Leigh syndrome associated with mitochondrial complex I deficiency due to novel mutations in NDUFV1 and NDUFS2. Gene 2013; 516: 162-167.
27. Laugel V, This-Bernd V, Cormier-Daire V, et al., Early-onset ophthalmoplegia in Leigh-like syndrome due to NDUFV1 mutations. Pediatr Neurol 2007; 36: 54-57.
28. Ma YY, Wu TF, Liu YP, et al., Two compound frame-shift mutations in succinate dehydrogenase gene of a Chinese boy with encephalopathy. Brain Dev 2014; 36: 394-398.
29. Bourgeron T, Rustin P, Chretien D, et al., Mutation of a nuclear succinate dehydrogenase gene results in mitochondrial respiratory chain deficiency. Nat Genet 1995; 11: 144-149.
30. Pagnamenta AT, Hargreaves IP, Duncan AJ, et al., Phenotypic variability of mitochondrial disease caused by a nuclear mutation in complex II. Mol Genet Metab 2006; 89: 214-221.
31. Koch J, Freisinger P, Feichtinger RG, et al., Mutations in TTC19: expanding the molecular, clinical and biochemical phenotype. Orphanet J Rare Dis 2015; 10: 40.
32. Van Maldergem L, Trijbels F, DiMauro S, et al., Coenzyme Q-responsive Leigh's encephalopathy in two sisters. Ann Neurol 2002; 52: 750-754.
33. 10 deficiency. Neuromuscul Disord 2012; 22: 76-86.
34. Leshinsky-Silver E, Levine A, Nissenkorn A, et al., Neonatal liver failure and Leigh syndrome possibly due to CoQ-responsive OXPHOS deficiency. Mol Genet Metab 2003; 79: 288-293.
35. Wedatilake Y, Brown R, McFarland R, et al., SURF1 deficiency: a multi-centre natural history study. Orphanet J Rare Dis 2013; 8: 96.
36. Rahman S, Brown RM, Chong WK, et al., A SURF1 gene mutation presenting as isolated leukodystrophy. Ann Neurol 2001; 49: 797-800.
37. Debray FG, Morin C, Janvier A, et al., LRPPRC mutations cause a phenotypically distinct form of Leigh syndrome with cytochrome c oxidase deficiency. J Med Genet 2011; 48: 183-189.
38. Mineri R, Rimoldi M, Burlina AB, et al., Identification of new mutations in the ETHE1 gene in a cohort of 14 patients presenting with ethylmalonic encephalopathy. J Med Genet 2008; 45: 473-478.
39. Pronicka E, Piekutowska-Abramczuk D, Szymanska-Debinska T, et al., The natural history of SCO2 deficiency in 36 Polish children confirmed the genotype-phenotype correlation. Mitochondrion 2013; 13: 810-816.
40. Mootha VK, Lepage P, Miller K, et al., Identification of a gene causing human cytochrome c oxidase deficiency by integrative genomics. Proc Natl Acad Sci U S A 2003; 100: 605-610.
41. Mourier A, Ruzzenente B, Brandt T, et al., Loss of LRPPRC causes ATP synthase deficiency. Hum Mol Genet 2014; 23: 2580-2592.
42. Garcia-Silva MT, Ribes A, Campos Y, et al., Syndrome of encephalopathy, petechiae, and ethylmalonic aciduria. Pediatr Neurol 1997; 17: 165-170.
43. Tiranti V, Viscomi C, Hildebrandt T, et al., Loss of ETHE1, a mitochondrial dioxygenase, causes fatal sulfide toxicity in ethylmalonic encephalopathy. Nat Med 2009; 15: 200-205.
44. Viscomi C, Burlina AB, Dweikat I, et al., Combined treatment with oral metronidazole and N-acetylcysteine is effective in ethylmalonic encephalopathy. Nat Med 2010; 16: 869-871.
45. Pitceathly RD, Rahman S, Wedatilake Y, et al., NDUFA4 mutations underlie dysfunction of a cytochrome c oxidase subunit linked to human neurological disease. Cell Rep 2013; 3: 1795-1805.
46. Elpeleg O, Miller C, Hershkovitz E, et al., Deficiency of the ADP-forming succinyl-CoA synthase activity is associated with encephalomyopathy and mitochondrial DNA depletion. Am J Hum Genet 2005; 76: 1081-1086.
47. Van Hove JL, Saenz MS, Thomas JA, et al., Succinyl-CoA ligase deficiency: a mitochondrial hepatoencephalomyopathy. Pediatr Res 2010; 68: 159-164.
48. Navarro-Sastre A, Tort F, Garcia-Villoria J, et al., Mitochondrial DNA depletion syndrome: new descriptions and the use of citrate synthase as a helpful tool to better characterise the patients. Mol Genet Metab 2012; 107: 409-415.
49. Valayannopoulos V, Haudry C, Serre V, et al., New SUCLG1 patients expanding the phenotypic spectrum of this rare cause of mild methylmalonic aciduria. Mitochondrion 2010; 10: 335-341.
50. Tucker EJ, Hershman SG, Kohrer C, et al., Mutations in MTFMT underlie a human disorder of formylation causing impaired mitochondrial translation. Cell Metab 2011; 14: 428-434.
51. Haack TB, Gorza M, Danhauser K, et al., Phenotypic spectrum of eleven patients and five novel MTFMT mutations identified by exome sequencing and candidate gene screening. Mol Genet Metab 2014; 111: 342-352.
52. Taylor RW, Morris AA, Hutchinson M, et al., Leigh disease associated with a novel mitochondrial DNA ND5 mutation. Eur J Hum Genet 2002; 10: 141-144.
53. Kirby DM, Boneh A, Chow CW, et al., Low mutant load of mitochondrial DNA G13513A mutation can cause Leigh's disease. Ann Neurol 2003; 54: 473-478.
54. Ruiter EM, Siers MH, van den Elzen C, et al., The mitochondrial 13513G > A mutation is most frequent in Leigh syndrome combined with reduced complex I activity, optic atrophy and/or Wolff-Parkinson-White. Eur J Hum Genet 2007; 15: 155-161.
55. Thorburn DR, Rahman S,. Mitochondrial DNA-associated Leigh syndrome and NARP. In:, Pagon RA, Adam MP, Ardinger HH, et al, eds. GeneReviews. Seattle, WA: University of Washington, 1993.
56. Tatuch Y, Christodoulou J, Feigenbaum A, et al., Heteroplasmic mtDNA mutation (T - - G) at 8993 can cause Leigh disease when the percentage of abnormal mtDNA is high. Am J Hum Genet 1992; 50: 852-858.
57. de Vries DD, van Engelen BG, Gabreels FJ, et al., A second missense mutation in the mitochondrial ATPase 6 gene in Leigh's syndrome. Ann Neurol 1993; 34: 410-412.
58. Koga Y, Koga A, Iwanaga R, et al., Single-fiber analysis of mitochondrial A3243G mutation in four different phenotypes. Acta Neuropathol 2000; 99: 186-190.
59. Hammans SR, Sweeney MG, Brockington M, et al., The mitochondrial DNA transfer RNA(Lys)A - >G(8344) mutation and the syndrome of myoclonic epilepsy with ragged red fibres (MERRF). Relationship of clinical phenotype to proportion of mutant mitochondrial DNA. Brain 1993; 116 (pt 3): 617-632.
60. Tulinius MH, Houshmand M, Larsson NG, et al., De novo mutation in the mitochondrial ATP synthase subunit 6 gene (T8993G) with rapid segregation resulting in Leigh syndrome in the offspring. Hum Genet 1995; 96: 290-294.
61. White SL, Shanske S, McGill JJ, et al., Mitochondrial DNA mutations at nucleotide 8993 show a lack of tissue- or age-related variation. J Inherit Metab Dis 1999; 22: 899-914.
62. Patel KP, O'Brien TW, Subramony SH, et al., The spectrum of pyruvate dehydrogenase complex deficiency: clinical, biochemical and genetic features in 371 patients. Mol Genet Metab 2012; 106: 385-394.
63. DeBrosse SD, Okajima K, Zhang S, et al., Spectrum of neurological and survival outcomes in pyruvate dehydrogenase complex (PDC) deficiency: lack of correlation with genotype. Mol Genet Metab 2012; 107: 394-402.
64. Willemsen M, Rodenburg RJ, Teszas A, et al., Females with PDHA1 gene mutations: a diagnostic challenge. Mitochondrion 2006; 6: 155-159.
65. Soreze Y, Boutron A, Habarou F, et al., Mutations in human lipoyltransferase gene LIPT1 cause a Leigh disease with secondary deficiency for pyruvate and alpha-ketoglutarate dehydrogenase. Orphanet J Rare Dis 2013; 8: 192.
66. Quinonez SC, Leber SM, Martin DM, et al., Leigh syndrome in a girl with a novel DLD mutation causing E3 deficiency. Pediatr Neurol 2013; 48: 67-72.
67. Baker PR Jr, Friederich MW, Swanson MA, et al., Variant non ketotic hyperglycinemia is caused by mutations in LIAS, BOLA3 and the novel gene GLRX5. Brain 2014; 137: 366-379.
68. Gerards M, Kamps R, van Oevelen J, et al., Exome sequencing reveals a novel Moroccan founder mutation in SLC19A3 as a new cause of early-childhood fatal Leigh syndrome. Brain 2013; 136: 882-890.
69. Mayr JA, Freisinger P, Schlachter K, et al., Thiamine pyrophosphokinase deficiency in encephalopathic children with defects in the pyruvate oxidation pathway. Am J Hum Genet 2011; 89: 806-812.
70. Zeng WQ, Al-Yamani E, Acierno JS Jr, et al., Biotin-responsive basal ganglia disease maps to 2q36.3 and is due to mutations in SLC19A3. Am J Hum Genet 2005; 77: 16-26.
71. Ortigoza-Escobar JD, Serrano M, Molero M, et al., Thiamine transporter-2 deficiency: outcome and treatment monitoring. Orphanet J Rare Dis 2014; 9: 92.
72. Fassone E, Wedatilake Y, DeVile CJ, et al., Treatable Leigh-like encephalopathy presenting in adolescence. BMJ Case Rep 2013; 2013: 200838.
73. Wang Z, Qi XK, Yao S, et al., Phenotypic patterns of MELAS/LS overlap syndrome associated with m.13513G>A mutation, and neuropathological findings in one autopsy case. Neuropathology 2010; 30: 606-614.
74. Santorelli FM, Barmada MA, Pons R, et al., Leigh-type neuropathology in Pearson syndrome associated with impaired ATP production and a novel mtDNA deletion. Neurology 1996; 47: 1320-1323.
75. Yamadori I, Kurose A, Kobayashi S, et al., Brain lesions of the Leigh-type distribution associated with a mitochondriopathy of Pearson's syndrome: light and electron microscopic study. Acta Neuropathol 1992; 84: 337-341.
76. Scalais E, Francois B, Schlesser P, et al., Polymerase gamma deficiency (POLG): clinical course in a child with a two stage evolution from infantile myocerebrohepatopathy spectrum to an Alpers syndrome and neuropathological findings of Leigh's encephalopathy. Eur J Paediatr Neurol 2012; 16: 542-548.
77. Taanman JW, Rahman S, Pagnamenta AT, et al., Analysis of mutant DNA polymerase gamma in patients with mitochondrial DNA depletion. Hum Mutat 2009; 30: 248-254.
78. Wortmann SB, Vaz FM, Gardeitchik T, et al., Mutations in the phospholipid remodeling gene SERAC1 impair mitochondrial function and intracellular cholesterol trafficking and cause dystonia and deafness. Nat Genet 2012; 44: 797-802.
79. Wortmann S, Rodenburg RJ, Huizing M, et al., Association of 3-methylglutaconic aciduria with sensori-neural deafness, encephalopathy, and Leigh-like syndrome (MEGDEL association) in four patients with a disorder of the oxidative phosphorylation. Mol Genet Metab 2006; 88: 47-52.
80. Loupatty FJ, Clayton PT, Ruiter JP, et al., Mutations in the gene encoding 3-hydroxyisobutyryl-CoA hydrolase results in progressive infantile neurodegeneration. Am J Hum Genet 2007; 80: 195-199.
81. Peters H, Buck N, Wanders R, et al., ECHS1 mutations in Leigh disease: a new inborn error of metabolism affecting valine metabolism. Brain 2014; 137 (pt 11): 2903-2908.
82. Ghezzi D, Sevrioukova I, Invernizzi F, et al., Severe X-linked mitochondrial encephalomyopathy associated with a mutation in apoptosis-inducing factor. Am J Hum Genet 2010; 86: 639-649.
83. 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: 260-266.
84. 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: 129-131.
85. Hernandez-Vazquez A, Wolf B, Pindolia K, et al., Biotinidase knockout mice show cellular energy deficit and altered carbon metabolism gene expression similar to that of nutritional biotin deprivation: clues for the pathogenesis in the human inherited disorder. Mol Genet Metab 2013; 110: 248-254.
86. Atamna H, Newberry J, Erlitzki R, et al., Biotin deficiency inhibits heme synthesis and impairs mitochondria in human lung fibroblasts. J Nutr 2007; 137: 25-30.
87. Depeint F, Bruce WR, Shangari N, et al., Mitochondrial function and toxicity: role of the B vitamin family on mitochondrial energy metabolism. Chem Biol Interact 2006; 163: 94-112.
88. Ferdinandusse S, Waterham HR, Heales SJ, et al., HIBCH mutations can cause Leigh-like disease with combined deficiency of multiple mitochondrial respiratory chain enzymes and pyruvate dehydrogenase. Orphanet J Rare Dis 2013; 8: 188.
89. Leonard WR, Robertson ML, Snodgrass JJ, et al., Metabolic correlates of hominid brain evolution. Comp Biochem Physiol A Mol Integr Physiol 2003; 136: 5-15.
90. Kuzawa CW, Chugani HT, Grossman LI, et al., Metabolic costs and evolutionary implications of human brain development. Proc Natl Acad Sci U S A 2014; 111: 13010-13015.
91. Chugani HT, Phelps ME, Mazziotta JC,. Positron emission tomography study of human brain functional development. Ann Neurol 1987; 22: 487-497.
92. Filosto M, Tomelleri G, Tonin P, et al., Neuropathology of mitochondrial diseases. Biosci Rep 2007; 27: 23-30.
93. Pagliarini DJ, Calvo SE, Chang B, et al., A mitochondrial protein compendium elucidates complex I disease biology. Cell 2008; 134: 112-123.
94. Zhang Z, Tsukikawa M, Peng M, et al., Primary respiratory chain disease causes tissue-specific dysregulation of the global transcriptome and nutrient-sensing signaling network. PloS One 2013; 8: e69282.
95. Carroll CJ, Brilhante V, Suomalainen A,. Next-generation sequencing for mitochondrial disorders. Br J Pharmacol 2014; 171: 1837-1853.
96. Wortmann SB, Koolen DA, Smeitink JA, et al., Whole exome sequencing of suspected mitochondrial patients in clinical practice. J Inherit Metab Dis 2015; 38: 437-443.
97. Johnson SC, Yanos ME, Kayser EB, et al., mTOR inhibition alleviates mitochondrial disease in a mouse model of Leigh syndrome. Science 2013; 342: 1524-1528.
98. Civiletto G, Varanita T, Cerutti R, et al., Opa1 overexpression ameliorates the phenotype of two mitochondrial disease mouse models. Cell Metab 2015; 21: 845-854.
99. Glushakova LG, Judge S, Cruz A, et al., Increased superoxide accumulation in pyruvate dehydrogenase complex deficient fibroblasts. Mol Genet Metab 2011; 104: 255-260.
100. Distelmaier F, Koopman WJ, van den Heuvel LP, et al., Mitochondrial complex I deficiency: from organelle dysfunction to clinical disease. Brain 2009; 132: 833-842.
101. Quintana A, Kruse SE, Kapur RP, et al., Complex I deficiency due to loss of Ndufs4 in the brain results in progressive encephalopathy resembling Leigh syndrome. Proc Natl Acad Sci U S A 2010; 107: 10996-11001.
102. Choi WS, Palmiter RD, Xia Z,. Loss of mitochondrial complex I activity potentiates dopamine neuron death induced by microtubule dysfunction in a Parkinson's disease model. J Cell Biol 2011; 192: 873-882.
103. Bird MJ, Wijeyeratne XW, Komen JC, et al., Neuronal and astrocyte dysfunction diverges from embryonic fibroblasts in the Ndufs4fky/fky mouse. Biosci Rep 2014; 34: e00151.
104. Lin AL, Pulliam DA, Deepa SS, et al., Decreased in vitro mitochondrial function is associated with enhanced brain metabolism, blood flow, and memory in Surf1-deficient mice. J Cereb Blood Flow Metab 2013; 33: 1605-1611.
105. Lightowlers RN, Chrzanowska-Lightowlers ZM,. Salvaging hope: is increasing NAD(+) a key to treating mitochondrial myopathy? EMBO Mol Med 2014; 6: 705-707.
106. Braidy N, Poljak A, Grant R, et al., Mapping NAD(+) metabolism in the brain of ageing Wistar rats: potential targets for influencing brain senescence. Biogerontology 2014; 15: 177-198.
107. Cerutti R, Pirinen E, Lamperti C, et al., NAD(+)-dependent activation of Sirt1 corrects the phenotype in a mouse model of mitochondrial disease. Cell Metab 2014; 19: 1042-1049.
108. Khan NA, Auranen M, Paetau I, et al., Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3. EMBO Mol Med 2014; 6: 721-731.
109. Rahman S,. Emerging aspects of treatment in mitochondrial disorders. J Inherit Metab Dis 2015; 38: 641-653.
110. Lopez-Armada MJ, Riveiro-Naveira RR, Vaamonde-Garcia C, et al., Mitochondrial dysfunction and the inflammatory response. Mitochondrion 2013; 13: 106-118.
111. Olsen RK, Cornelius N, Gregersen N,. Redox signalling and mitochondrial stress responses; lessons from inborn errors of metabolism. J Inherit Metab Dis 2015; 38: 703-719.
112. Pfeffer G, Majamaa K, Turnbull DM, et al., Treatment for mitochondrial disorders. Cochrane Database Syst Rev 2012; 4: CD004426.
113. Niezgoda J, Morgan PG,. Anesthetic considerations in patients with mitochondrial defects. Paediatr Anaesth 2013; 23: 785-793.
114. 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: 209-222.
115. Carrozzo R, Dionisi-Vici C, Steuerwald U, et al., SUCLA2 mutations are associated with mild methylmalonic aciduria, Leigh-like encephalomyopathy, dystonia and deafness. Brain 2007; 130: 862-874.
116. Ivanov IS, Azmanov DN, Ivanova MB, et al., Founder p.Arg 446∗ mutation in the PDHX gene explains over half of cases with congenital lactic acidosis in Roma children. Mol Genet Metab 2014; 113: 76-83.