REFERENCES

1. Lienhart WD, Gudipati V, Macheroux P. The human flavoproteome. Arch Biochem Biophys 2013;535:150-62.

2. Joosten V, van Berkel WJ. Flavoenzymes. Curr Opin Chem Biol 2007;11:195-202.

3. Balasubramaniam S, Christodoulou J, Rahman S. Disorders of riboflavin metabolism. J Inherit Metab Dis 2019;42:608-19.

4. Kennedy DO. B Vitamins and the brain: mechanisms, dose and efficacy-a review. Nutrients 2016;8:68.

5. Barile M, Giancaspero TA, Leone P, Galluccio M, Indiveri C. Riboflavin transport and metabolism in humans. J Inherit Metab Dis 2016;39:545-57.

6. Henriques BJ, Rodrigues JV, Gomes CM. Riboflavin and b-oxidation flavoenzymes. In: Preedy VR, editor. B vitamins and folate: chemistry, analysis, function and effects (Food and nutritional components in focus series No. 4). Cambridge: The Royal Society of Chemistry Publishing; 2013. pp. 611-30.

7. Mosegaard S, Dipace G, Bross P, Carlsen J, Gregersen N, et al. Riboflavin Deficiency-Implications for general human health and inborn errors of metabolism. Int J Mol Sci 2020;21:E3847.

8. McCormick DB. Two interconnected B vitamins: riboflavin and pyridoxine. Physiol Rev 1989;69:1170-98.

9. Zempleni J, Galloway JR, McCormick DB. Pharmacokinetics of orally and intravenously administered riboflavin in healthy humans. Am J Clin Nutr 1996;63:54-66.

10. Powers HJ. Riboflavin (vitamin B-2) and health. Am J Clin Nutr 2003;77:1352-6130.

11. Chastain JL, McCormick DB. Flavin catabolites: identification and quantitation in human urine. Am J Clin Nutr 1987;46:830-4.

12. Suomalainen A, Battersby BJ. Mitochondrial diseases: the contribution of organelle stress responses to pathology. Nat Rev Mol Cell Biol 2017;19:77-92.

13. Gorman GS, Chinnery PF, DiMauro S, Hirano M, Kogaet Y, et al. Mitochondrial diseases. Nat Rev Dis Primers 2016;2:16080.

14. Hatefi Y. The mitochondrial electron transport and oxidative phosphorylation system. Annu Rev Biochem 1985;54:1015-69.

15. Van Houten B, Woshner V, Santos JH. Role of mitochondrial DNA in toxic responses to oxidative stress. DNA Repair (Amst) 2006;5:145-52.

16. Ross WN. Understanding calcium waves and sparks in central neurons. Nat Rev Neurosci 2012;13:157-68.

17. Niyazov DM, Kahler SG, Frye R. Primary mitochondrial disease and secondary mitochondrial dysfunction: importance of distinction for diagnosis and treatment. Mol Syndromol 2016;7:122-37.

18. Yonezawa A, Masura S, Katsura T, Inui K. Identification and functional characterization of a novel human and rat riboflavin transporter, RFT1. Am J Physiol Cell Physiol 2008;295:C632-41.

19. Yonezawa A, Inui K. Novel riboflavin transporter family RFVT/SLC52: identification, nomenclature, functional characterization and genetic diseases of RFVT/SLC52. Mol Aspects Med 2013;34:693-701.

20. Yamamoto S, Inque K, Ohta KY, Fukatsu R, Maeda J, et al. Identification and functional characterization of rat riboflavin transporter 2. J Biochem 2009;145:437-43.

21. Yao Y, Yonezawa A, Yoshimatsu H, Masuda S, Katsura T, et al. Identification and comparative functional characterization of a new human riboflavin transporter hRFT3 expressed in the brain. J Nutr 2010;140:1220-6.

22. Bosch AM, Abeling NG, Ijlst L, Knoester H, van der Pol WL, et al. Brown-Vialetto-Van Laere and Fazio Londe syndrome is associated with a riboflavin transporter defect mimicking mild MADD: a new inborn error of metabolism with potential treatment. J Inherit Metab Dis 2011;34:159-64.

23. Green P, Wiseman M, Crow YJ, Houlden H, Riphagenet S, et al. Brown-Vialetto-Van Laere syndrome, a ponto-bulbar palsy with deafness, is caused by mutations in c20orf54. Am J Hum Genet 2010;86:485-9.

24. Dipti S, Childs AM, Livingston JH, Aggarwal AK, Miller M, et al. Brown-Vialetto-Van Laere syndrome; variability in age at onset and disease progression highlighting the phenotypic overlap with Fazio-Londe disease. Brain Dev 2005;27:443-6.

25. Manole A, Houlden H. Riboflavin transporter deficiency neuronopathy. In: GeneReviews® [Internet]. Seattle (WA): University of Washington; .

26. O’Callaghan B, Bosch AM, Houlden H. An update on the genetics, clinical presentation, and pathomechanisms of human riboflavin transporter deficiency. J Inherit Metab Dis 2019;42:598-607.

27. Chiong MS, Sim KG, Carpenter K, Rhead W, Ho G, et al. Transient multiple acyl-CoA dehydrogenation deficiency in a newborn female caused by maternal riboflavin deficiency. Mol Genet Metab 2007;92:109-14.

28. Ho G, Yonezawa A, Masuda S, Inui K, Sim KG, et al. Maternal riboflavin deficiency, resulting in transient neonatal-onset glutaric aciduria Type 2, is caused by a microdeletion in the riboflavin transporter gene GPR172B. Hum Mutat 2011;32:E1976-84.

29. Mosegaard S, Bruun GH, Flybjerg KF, Bliksrud YT, Gregersen N, et al. An intronic variation in SLC52A1 causes exon skipping and transient riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency. Mol Genet Metab 2017;122:182-8.

30. Schiff M, Veauville-Merllie A, Acquaviva-Bourdain C. SLC25A32 mutations and riboflavin-responsive exercise intolerance. N Engl J Med 2016;374:795-7.

31. Hellebrekers DMEI, Sallevelt SCEH, Theunissen TEJ, Hendrickx ATM, Gottschalk RW, et al. Novel SLC25A32 mutation in a patient with a severe neuromuscular phenotype. Eur J Hum Genet 2017;25:886-8.

32. Santoro V, Kovalenko I, Vriens K, Christen S, Bernthaler A, et al. SLC25A32 sustains cancer cell proliferation by regulating flavin adenine nucleotide (FAD) metabolism. Oncotarget 2020;11:801-12.

33. Giancaspero TA, Colella M, Brizio C, Difonzo G, Fiorino GM, et al. Remaining challenges in cellular flavin cofactor homeostasis and flavoprotein biogenesis. Front Chem 2015;22:30.

34. Olsen RKJ, Konarikova E, Giancaspero TA, Mosegaard S, Boczonadi V, et al. Riboflavin responsive and-non-responsive mutations in FAD synthase cause multiple acyl-CoA dehydrogenase and combined respiratory-chain deficiency. Am J Hum Genet 2016;98:1130-45.

35. Torchetti EM, Brizio C, Colella M, Galluccio M, Giancaspero TA, et al. Mitochondrial localization of human FAD synthetase isoform 1. Mitochondrion 2010;10:263-73.

36. Giancaspero TA, Busco G, Panebianco C, Carmone C, Miccolis A, et al. FAD synthesis and degradation in the nucleus create a local flavin cofactor pool. J Biol Chem 2013;288:29069-80.

37. Leone P, Galluccio M, Barbiroli A, Eberini I, Tolomeo M, et al. Bacterial production, characterization and protein modeling of a novel monofunctional isoform of FAD synthase in humans: an emergency protein? Molecules 2018;23:116-31.

38. Torchetti EM, Bonomi F, Galluccio M, Gianazza E, Giancaspero TA, et al. Human FAD synthase (isoform 2): a component of the machinery that delivers FAD to apo-flavoproteins. FEBS J 2011;278:4434-49.

39. Taylor RW, Pyle A, Griffin H, Blakely EL, Duff J, et al. Use of whole-exome sequencing to determine the genetic basis of multiple mitochondrial respiratory chain complex deficiencies. JAMA 2014;312:68-77.

40. Auranen MA, Paetau A, Piirilä P, Pohju A, Salmi T, et al. Patient with multiple acyl-CoA dehydrogenation deficiency disease and FLAD1 mutations benefits from riboflavin therapy. Neuromuscul Disord 2017;27:581-4.

41. Yildiz Y, Olsen RKJ, Sivri HS, Akçören Z, Nygaard HH, et al. Post-mortem detection of FLAD1 mutations in 2 Turkish siblings with hypotonia in early infancy. Neuromuscul Disord 2018;28:787-90.

42. Ryder B, Tolomeo M, Nochi Z, Colella M, Barile M, et al. A novel truncating FLAD1 variant, causing multiple Acyl-CoA dehydrogenase deficiency (MADD) in an 8-year-old boy. JIMD Rep 2019;45:37-44.

43. García-Villoria J, De Azua B, Tort F, Mosegaard S, Ugarteburu O, et al. FLAD1, encoding FAD synthase, is mutated in a patient with myopathy, scoliosis and cataracts. Clin Genet 2018;94:592-3.

44. Muru K, Reinson K, Künnapas K, Lilleväli H, Nochi Z, et al. FLAD1-associated multiple acyl-CoA dehydrogenase deficiency identified by newborn screening. Mol Genet Genomic Med 2019;7:e915.

45. Yamada K, Ito M, Kobayashi H, Hasegawa Y, Fukuda S, et al. Flavin adenine dinucleotide synthase deficiency due to FLAD1 mutation presenting as multiple acyl-CoA dehydrogenation deficiency-like disease: a case report. Brain Dev 2019;41:638-42.

46. Karthikeyan S, Zhou Q, Mseeh F, Grishin NV, Osterman AL, et al. Crystal structure of human riboflavin kinase reveals a beta barrel fold and a novel active site arch. Structure 2003;11:265-73.

47. Yazdanpanah B, Wiegmann K, Tchikov V, Krut O, Pongratz C, et al. Riboflavin kinase couples TNF receptor 1 to NADPH oxidase. Nature 2009;460:1159-63.

48. Zhang J, Zhang W, Zou D, Chen G, Wan T, et al. Cloning and functional characterization of ACAD-9, a novel member of human acyl-CoA dehydrogenase family. Biochem. Biophys Res Commun 2002;297:1033-42.

49. Schiff M, Haberberger B, Xia CW, Mohsen AW, Goetzman ES, et al. Complex I assembly function and fatty acid oxidation enzyme activity of ACAD9 both contribute to disease severity in ACAD9 deficiency. Hum Mol Genet 2015;24:3238-47.

50. Nouws J, Te Brinke H, Nijtmans LG, Houten SM. ACAD9, a complex I assembly factor with a moonlighting function in fatty acid oxidation deficiencies. Hum Mol Genet 2014;23:1311-9.

51. Repp BM, Mastantuono E, Alston CL, Schiff M, Haack TB, et al. Clinical, biochemical and genetic spectrum of 70 patients with ACAD9 deficiency: is riboflavin supplementation effective? Orphanet J Rare Dis 2018;13:120.

52. Oey NA, Ruiter JP, Ijlst L, Attie-Bitach T, Vekemans M, et al. Acyl-CoA dehydrogenase 9 (ACAD 9) is the long-chain acyl-CoA dehydrogenase in human embryonic and fetal brain. Biochem Biophys Res Commun ;346:33-7.

53. Lemire BD. Evolution of FOXRED1, an FAD-dependent oxidoreductase necessary for NADH: Ubiquinone oxidoreductase (Complex I) assembly. Biochim. Biophys Acta ;1847:451-7.

54. Lemire BD. Glutathione metabolism links FOXRED1 to NADH: ubiquinone oxidoreductase (complex I) deficiency: a hypothesis. Mitochondrion ;24:105-12.

55. Barbosa-Gouveia S, González-Vioque E, Borges F, Gutiérrez-Solana L, Wintjes L, et al. Identification and characterization of new variants in FOXRED1 gene expands the clinical spectrum associated with mitochondrial complex I deficiency. J Clin Med 2019;8:1262.

56. Calvo SE, Tucker EJ, Compton AG, Kirby DM, Crawford G, et al. High-throughput, pooled sequencing identifies mutations in NUBPL and FOXRED1 in human complex I deficiency. Nat Genet 2010;42:851-8.

57. Fassone E, Duncan AJ, Taanman JW, Pagnamenta AT, Sadowski MI, et al. FOXRED1, encoding an FAD-dependent oxidoreductase complex-I-specific molecular chaperone, is mutated in infantile-onset mitochondrial encephalopathy. Hum Mol Genet 2010;19:4837-47.

58. Haack TB, Madignier F, Herzer M, Lamantea E, Danhauser K, et al. Mutation screening of 75 candidate genes in 152 complex I deficiency cases identifies pathogenic variants in 16 genes including NDUFB9. J Med Genet 2012;49:83-9.

59. Zurita Rendón O, Antonicka H, Horvath R, Shoubridge EA. A mutation in the flavin adenine dinucleotide-dependent oxidoreductase FOXRED1 results in cell-type-specific assembly defects in oxidative phosphorylation complexes I and II. Mol Cell Biol 2016;36:2132-40.

60. Apatean D, Rakic B, Brunel-Guitton C, Hendson G, Bai R, et al. Congenital lactic acidosis, cerebral cysts and pulmonary hypertension in an infant with FOXRED1 related complex I deficiency. Mol Genet Metab Rep 2019;18:32-8.

61. Formosa LE, Mimaki M, Frazier AE, McKenzie M, Stait TL, et al. Characterization of mitochondrial FOXRED1 in the assembly of respiratory chain complex I. Hum Mol Genet 2015;24:2952-65.

62. Bentinger M, Brismar K, Dallner G. The antioxidant role of coenzyme Q. Mitochondrion 2007;7 Suppl:S41-50.

63. Turunen M, Olsson J, Dallner G. Metabolism and function of coenzyme Q. Biochim Biophys Act 2004;1660:171-99.

64. Acosta Lopez MJ, Trevisson E, Canton M, Vazquez-Fonseca L, Morbidoniet V, et al. Vanillic acid restores coenzyme q biosynthesis and ATP production in human cells lacking COQ6. Oxid Med Cell Longe 2019;2019:3904905.

65. Heeringa SF, Chernin G, Chaki M, Zhou W, Sloan AJ, et al. COQ6 mutations in human patients produce nephrotic syndrome with sensorineural deafness. J Clin Invest 2011;121:2013-24.

66. Cao Q, Li GM, Xu H, Shen Q, Sun L, et al. Coenzyme Q (10) treatment for one child with COQ6 gene mutation induced nephrotic syndrome and literature review. Zhonghua Er Ke Za Zhi 2017;55:135-8. (in Chinese)

67. Gigante M, Diella S, Santangelo L, Trevisson E, Acosta MJ, et al. Further phenotypic heterogeneity of CoQ10 deficiency associated with steroid resistant nephrotic syndrome and novel COQ2 and COQ6 variants. Clin Genet 2017;92:224-6.

68. Park E, Ahn YH, Kang HG, Yoo KH, Won NH, et al. COQ6 mutations in children with steroid-resistant focal segmental glomerulosclerosis and sensorineural hearing loss. Am J Kidney Di 2017;70:139-44.

69. Li GM, Cao Q, Shen Q, Sun L, Zhai YH, et al. Gene mutation analysis in 12 Chinese children with congenital nephrotic syndrome. BMC Nephro 2018;19:382.

70. Stanczyk M, Balasz-Chemielewska I, Lipska-Zietkiewicz B, Tkaczyk M. CoQ10-related sustained remission of proteinuria in a child with COQ6 glomerulopathy-a case report. Pediatr Nephrol 2018;33:2383-7.

71. Yuruk Yildirim Z, Toksoy G, Uyguner O, Nayir A, Yavuz S, et al. Primary coenzyme Q10 Deficiency-6 (COQ10D6): two siblings with variable expressivity of the renal phenotype. Eur J Med Genet 2020;63:103621.

72. Koyun M, Çomak E, Akman S. CoenzymeQ10 therapy in two sisters with CoQ6 mutations with long-term follow-up. Pediatr Nephrol 2019;34:737-8.

73. Ozeir M, Muhlenhoff U, Webert H, Lill R, Fontecave M, et al. Coenzyme Q biosynthesis: Coq6 is required for the C5-hydroxylation reaction and substrate analogs rescue Coq6 deficiency. Chem Biol 2011;18:1134-42.

74. Ozaltin F. Primary coenzyme Q10 (CoQ 10) deficiencies and related nephropathies. Pediatr Nephrol 2014;29:961-9.

75. Herrmann JM, Riemer J. Mitochondrial disulfide relay: redox-regulated protein import into the intermembrane space. J Biol Chem ;287:4426-33.

76. Bihlmaier K, Mesecke N, Terziyska N, Bien M, Hell K, et al. The disulfide relay system of mitochondria is connected to the respiratory chain. J Cell Biol 2007;179:389-95.

77. Di Fonzo A, Ronchi D, Lodi T, Fassone E, Tigano M, 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.

78. Ceh-Pavia E, Ang SK, Spiller MP, Lu H. The disease-associated mutation of the mitochondrial thiol oxidase Erv1 impairs cofactor binding during its catalytic reaction. Biochem J 2014;464:449-59.

79. Daithanka VN, Schaefer SA, Dong M, Bahnson BJ, Thorpe C. Structure of the human sulfhydryl oxidase augmenter of liver regeneration and characterization of a human mutation causing an autosomal recessive myopathy. Biochemistry 2010;49:6737-45.

80. Calderwood L, Holm IA, Teot LA, Anselm I. Adrenal insufficiency in mitochondrial disease: a rare case of GFER-related mitochondrial encephalomyopathy and review of the literature. J Child Neurol 2016;31:190-4.

81. Nambot S, Gavrilov D, Thevenon J. Further delineation of a rare recessive encephalomyopathy linked to mutations in GFER thanks to data sharing of whole exome sequencing data. Clin Genet 2017;92:188-98.

82. Stehling O, Wilbrecht C, Lill R. Mitochondrial iron-sulfur protein biogenesis and human disease. Biochimie 2014;100:61-77.

83. Hanukoglu I, Jefcoate CR. Mitochondrial cytochrome P-450scc. Mechanism of electron transport by adrenodoxin. J Biol Chem 1980;255:3057-61.

84. Paul A, Drecourt A, Petit F. FDXR mutations cause sensorial neuropathies and expand the spectrum of mitochondrial fe-s-synthesis diseases. Am J Hum Genet 2017;101:630-7.

85. Peng Y, Shinde DN, Valencia AC. Biallelic mutations in the ferredoxin reductase gene cause novel mitochondriopathy with optic atrophy. Human Molecular Genetics 2017;26:4937-50.

86. Slone J, Peng Y, Chamberlin A. Biallelic mutations in FDXR cause neurodegeneration associated with inflammation. J Hum Genet 2018;63:1211-22.

87. Brandt U. Energy converting NADH: quinone oxidoreductase (complex I). Annu Rev Biochem 2006;75:69-92.

88. Scheulke M, Smeitink J, Mariman E, Loeffen J, Plecko B, et al. Mutant NDUFV1 subunit of mitochondrial complex I causes leukodystrophy and myoclonic epilepsy. Nat Genet 1999;21:260-1.

89. Bénit P, Chretien D, Kadhom N, De-Lonlay-Debeney P, Cormier-Daire V, et al. Large-scale deletion and point mutations of the nuclear NDUFV1 and NDUFS1 genes in mitochondrial complex I deficiency. Am J Hum Genet 2001;68:1344-52.

90. Bindu PS, Sonam K, Chiplunkar S. Mitochondrial leukoencephalopathies: a border zone between acquired and inherited white matter disorders in children? Mult Scler Relat Disord 2018;20:84-92.

91. Björkman K, Sofou K, Darin N, Holme E, GKollberg G, et al. Broad phenotypic variability in patients with complex I deficiency due to mutations in NDUFS1 and NDUFV1. Mitochondrion 2015;21:33-40.

92. Breningstall GN, Shoffner J, Patterson RJ. Siblings with leukoencephalopathy. Semin Pediatr Neurol 2008;15:212-5.

93. Bugiani M, Invernizzi F, Alberio S, Briem E, Lamantea E, et al. Clinical and molecular findings in children with complex I deficiency. Biochim Biophys Acta 2004;1659:136-47.

94. Dinwiddie DL, Smith LD, Miller NA, Atherton AM, Farrow EG, et al. Diagnosis of mitochondrial disorders by concomitant next-generation sequencing of the exome and mitochondrial genome. Genomics 2013;102:148-56.

95. Incecik F, Herguner OM, Besen S. Late-onset leigh syndrome due to NDUFV1 mutation in a 10-year-old boy initially presenting with ataxia. J Pediatr Neurosci 2018;13:205-7.

96. Koene S, Rodenburg RJ, Van der Knaap MS, Willemsen MAAP, Sperl W, 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;35:737-47.

97. Lal D, Becker K, Motameny S, Altmüller J, Thiele H, et al. Homozygous missense mutation of NDUFV1 as the cause of infantile bilateral striatal necrosis. Neurogenetics 2013;14:85-7.

98. Laugel V, This-Bernd V, Cormier-Daire V, Speeg-Schatz C, de Saint-Martin A, et al. Early-onset ophthalmoplegia in Leigh-like syndrome due to NDUFV1 mutations. Pediatr Neurol 2007;36:54-7.

99. Lee JS, Yoo T, Lee M, Lee Y, Jeon E, et al. Genetic heterogeneity in Leigh syndrome: Highlighting treatable and novel genetic causes. Clin Genet 2020;97:586-94.

100. Lieber DS, Calvo SE, Shanahan K, Slate NG, Liu S, et al. Targeted exome sequencing of suspected mitochondrial disorders. Neurology 2013;80:1762-70.

101. Marin SE, Mesterman R, Robinson B, Rodenburg RJ, Smeitink J, et al. Leigh syndrome associated with mitochondrial complex I deficiency due to novel mutations In NDUFV1 and NDUFS2. Gene 2013;516:162-7.

102. Moran M, Rivera H, Sanchez-Arago M, Blázquez A, Merinero B, et al. Mitochondrial bioenergetics and dynamics interplay in complex I-deficient fibroblasts. Biochim Biophys Acta 2010;1802:443-53.

103. Nafisinia M, Guo Y, Dang X, Li J, Chen Y, et al. Whole exome sequencing identifies the genetic basis of late-onset leigh syndrome in a patient with MRI but little biochemical evidence of a mitochondrial disorder. JIMD Rep 2017;32:117-24.

104. Ortega-Recalde O, Fonseca DJ, Patino LC, Atuesta JJ, Rivera-Nieto C, et al. A novel familial case of diffuse leukodystrophy related to NDUFV1 compound heterozygous mutations. Mitochondrion 2013;13:749-54.

105. Pronicka E, Piekutowska-Abramczuk D, Ciara E, Trubicka J, Rokicki D, et al. New perspective in diagnostics of mitochondrial disorders: two years’ experience with whole-exome sequencing at a national paediatric centre. J Transl Me 2016;14:174.

106. Rubio-Gozalbo ME, Ruitenbeek W, Wendel U, Sengers RC, Trijbels JM, et al. Systemic infantile complex I deficiency with fatal outcome in two brothers. Neuropediatrics 1998;29:43-5.

107. Vilain C, Rens C, Abey A, Balériaux D, Van Bogaert P, et al. A novel NDUFV1 gene mutation in complex I deficiency in consanguineous siblings with brainstem lesions and Leigh syndrome. Clin Genet 2012;82:264-70.

108. Zafeiriou DI, Rodenburg RJ, Scheffer H, van den Heuvel LP, Pouwels PJW, et al. MR spectroscopy and serial magnetic resonance imaging in a patient with mitochondrial cystic leukoencephalopathy due to complex I deficiency and NDUFV1 mutations and mild clinical course. Neuropediatrics 2008;39:172-5.

109. Zhang J, Liu M, Zhang Z, Zhou L, Kong W, et al. Genotypic spectrum and natural history of cavitating leukoencephalopathies in childhood. Pediatr Neurol 2019;94:38-47.

110. Loeffen JL, Smeitink JS, Trijbels JM, Janssen AJ, Triepels RH, et al. Isolated complex I deficiency in children: clinical, biochemical, and genetic aspects. Hum Mutat 2000;15:123-34.

111. Bénit P, Chretien D, Kadhom N, Giurgea I, De Lonlay-Debeney P, et al. Mutant NDUFV2 subunit of mitochondrial complex I causes early onset hypertrophic cardiomyopathy and encephalopathy. Hum Mutat 2003;21:582-6.

112. Pagniez-Mammeri H, Lombes A, Brivet M, Ogier-de Baulny H, Landrieu P, et al. Rapid screening for nuclear genes mutations in isolated respiratory chain complex I defects. Mol Genet Metab 2009;96:196-200.

113. Cameron JM, Mackay N, Feigenbaum A, Tarnopolsky M, Blaseret S, et al. Exome sequencing identifies complex I NDUFV2 mutations as a novel cause of Leigh syndrome. Eur J Paediatr Neurol 2015;19:525-32.

114. Liu HY, Liao PC, Chuang KT, Kao MC. Mitochondrial targeting of human NADH dehydrogenase (ubiquinone) flavoprotein 2 (NDUFV2) and its association with early-onset hypertrophic cardiomyopathy and encephalopathy. J Biomed Sci 2011;18:29.

115. Aldera AP, Govender D. Gene of the month: SDH. J Clin Pathol 2018;7:95-7.

116. Evenepoel L, Papathomas TG, Krol N, Korpershoek E, de Krijger RR, et al. Toward an improved definition of the genetic and tumor spectrum associated with SDH germ-line mutations. Genet Med 2015;17:610-20.

117. Bausch B, Schiavi F, Ni Y, Welander J, Patocs A, et al. Clinical characterization of the pheochromocytoma and paraganglioma susceptibility genes SDHA, TMEM127, MAX, and SDHAF2 for gene-informed prevention. JAMA Oncol 2017;3:1204-12.

118. Burnichon N, Briere JJ, Libe R, Vescovo L, Rivière J, et al. SDHA is a tumor suppressor gene causing paraganglioma. Hum Mol Genet 2010;19:3011-20.

119. Dwight T, Mann K, Benn DE, Robinson BG, McKelvie P, et al. Familial SDHA mutation associated with pituitary adenoma and pheochromocytoma/paraganglioma. J Clin Endocrinol Metab 2013;98:E1103-8.

120. Gill AJ. Succinate dehydrogenase (SDH)-deficient neoplasia. Histopathology 2018;72:106-16.

121. Ozluk Y, Taheri D, Matosi A, Sanli O, Berker NK, et al. Renal carcinoma associated with a novel succinate dehydrogenase A mutation: a case report and review of literature of a rare subtype of renal carcinoma. Hum Pathol 2015;46:1951-5.

122. Burgeois M, Goutieres F, Chretien D, Rustin P, Munnich A, et al. Deficiency in complex II of the respiratory chain, presenting as a leukodystrophy in two sisters with Leigh syndrome. Brain Dev 1992;14:404-8.

123. Bourgeron T, Rustin P, Chretien D, Birch-Machin M, Bourgeois M, et al. Mutation of a nuclear succinate dehydrogenase gene results in mitochondrial respiratory chain deficiency. Nat Genet 1995;11:144-9.

124. Alston CL, Davison JE, Meloni F, van der Westhuizen FH, He L, et al. Recessive germline SDHA and SDHB mutations causing leukodystrophy and isolated mitochondrial complex II deficiency. J Med Genet 2012;49:569-77.

125. Helman G, Caldovic L, Whitehead MT, Simons C, Brockmann K, et al. Magnetic resonance imaging spectrum of succinate dehydrogenase-related infantile leukoencephalopathy. Ann Neurol 2016;79:379-86.

126. Horvath R, Abicht A, Holinski-Feder E, Laner A, Gempel K, et al. Leigh syndrome caused by mutations in the flavoprotein (Fp) subunit of succinate dehydrogenase (SDHA). J Neurol Neurosurg Psychiatry 2006;77:74-6.

127. Ma YY, Wu TF, Liu YP, Wang Q, Li XY, et al. Two compound frame-shift mutations in succinate dehydrogenase gene of a Chinese boy with encephalopathy. Brain Dev 2014;36:394-8.

128. Renkema GH, Wortmann SB, Smeets RJ, Venselaar H, Antoine M, et al. SDHA mutations causing a multisystem mitochondrial disease: novel mutations and genetic overlap with hereditary tumors. Eur J Hum Genet 2015;23:202-9.

129. Van Coster R, Seneca S, Smet J, Van Hecke R, Gerlo E, et al. Homozygous Gly555Glu mutation in the nuclear encoded 70 kDa flavoprotein gene causes instability of the respiratory chain complex II. Am J Med Genet A 2003;120A:13-8.

130. Pagnamenta AT, Hargreaves IP, Duncan AJ, Taanman JW, Heales SJ, et al. Phenotypic variability of mitochondrial disease caused by a nuclear mutation in complex II. Mol Genet Metab 2006;89:214-21.

131. Parfait B, Chretein D, Rotig A, Marsac C, Munnich A, et al. Compound heterozygous mutations in the flavoprotein gene of the respiratory chain complex II in a patient with Leigh syndrome. Hum Genet 2000;106:236-43.

132. Levitas A, Muhammad E, Harel G, Saada A, Caspi VC, et al. Familial neonatal isolated cardiomyopathy caused by a mutation in the flavoprotein subunit of succinate dehydrogenase. Eur J Hum Genet 2010;18:1160-5.

133. Taylor RW, Birch-Machin MA, Schaefer J, Taylor L, Shakir R, et al. Deficiency of complex II of the mitochondrial respiratory chain in late-onset optic atrophy and ataxia. Ann Neurol 1996;39:224-32.

134. Birch-Machin MA, Taylor RW, Cochran B, Ackrell BA, Turnbull DM. Late-onset optic atrophy, ataxia, and myopathy associated with a mutation of a complex II gene. Ann Neurol 2000;48:330-5.

135. Courage C, Jackson CB, Hahn D, Euro L, Nuoffer JM, et al. SDHA mutation with dominant transmission results in complex II deficiency with ocular, cardiac, and neurologic involvement. Am J Med Genet A 2017;173:225-30.

136. Olsen RK, Andresen BS, Christensen E, Bross P, Skovby F, et al. Clear relationship between ETF/ETFDH genotype and phenotype in patients with multiple acyl-CoA dehydrogenation deficiency. Hum Mutat 2003;22:12-23.

137. Frerman FE, Goodman SI. The Metabolic and Molecular Bases of Inherited Disease. In: Scriver CR, Sly WS, Childs B, Beaudet AL, Valle D, Kinzler KW, Vogelstein B, editors. 2001. Defects of Electron Transfer Flavoprotein and Electron Transfer Flavoprotein-Ubiquinone Oxidoreductase: Glutaric Acidemia Type II. Available from: https://ommbid.mhmedical.com/content.aspx?bookid=2709&sectionid=225088261. [Last accessed on 27 Jul 2020].

138. Grünert SC. Clinical and genetical heterogeneity of late-onset multiple acyl-coenzyme dehydrogenase deficiency. Orphanet J Rare Dis 2014;9:117.

139. Morris AAM, Spiekerkoetter U. Disorders of mitochondrial fatty acid oxidation and Related Metabolic Pathways. In: Saudubray JM, van den Berghe G, Walter JH, editors. Inborn metabolic diseases: diagnosis and treatment. Berlin: Springer; 2016.

140. Horvath R. Update on clinical aspects and treatment of selected vitamin-responsive disorders II (riboflavin and CoQ10). J Inherit Metab Dis 2012;35:679-87.

141. Cornelius N, Corydon TJ, Gregersen N, Olsen RKJ. Cellular consequences of oxidative stress in riboflavin responsive multiple acyl-CoA dehydrogenation deficiency patient fibroblasts. Hum Mol Genet 2014;23:4285-301.

142. Cameron JM, Levandovskiy V, Mackay N, Raiman J, Renaud DL, et al. Novel mutations in dihydrolipoamide dehydrogenase deficiency in two cousins with borderline normal PDH complex activity. Am J Med Genet A 2015;140:1542-52.

143. Quinonez SC, Thoene JG. Dihydrolipoamide dehydrogenase deficiency. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews® [Internet]. 2014. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK220444/. [Last accessed on 27 Jul 2020].

144. De Meirleir LJ, Garcia-Cazorla A, Brivet M. Disorders of pyruvate metabolism and the tricarboxylic acid cycle. Inborn metabolic diseases: diagnosis and treatment. In: Saudubray JM, Baumgartner MR, Walter J, editors. Berlin: Springer; 2016. pp. 161-74.

145. Quintana E, Pineda M, Font A, Vilaseca MA, Tort F, et al. Dihydrolipoamide dehydrogenase (DLD) deficiency in a Spanish patient with myopathic presentation due to a new mutation in the interface domain. J Inherit Metab Dis 2010;33:S315-9.

146. Carrozzo R, Torraco A, Fiermonte G, Martinelli D, Nottia MD, et al. Riboflavin responsive mitochondrial myopathy is a new phenotype of dihydrolipoamide dehydrogenase deficiency. The chaperon-like effect of vitamin B2. Mitochondrion 2014;18:49-57.

147. Tiranti V, Viscomi C, Hildebrandt T, Di Meo I, Mineri R, et al. Loss of ETHE1, a mitochondrial dioxygenase, causes fatal sulfide toxicity in ethylmalonic encephalopathy. Nat Med 2009;15:200-5.

148. Di Meo I, Lamperti C, Tiranti V. Ethylmalonic encephalopathy. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews [Internet] 2017. Seattle (WA): University of Washington; .

149. Kožich V, Ditrói T, Sokolová J, Křížková M, Krijt J, et al. Metabolism of sulfur compounds in homocystinurias. Br J Pharmacol 2019;176:594-606.

150. Viscomi C, Burlina AB, Dweikat I, Savoiardo M, Lamperti C, et al. Combined treatment with oral metronidazole and N-ace-tylcysteine is effective in ethylmalonic encephalopathy. Nat Med 2010;16:869-71.

151. Di Meo I, Lamperti C, Tiranti V. Mitochondrial diseases caused by toxic compound accumulation: from etiopathology to therapeutic approaches. EMBO Mol Med 2015;7:1257-66.

152. Yoon HR, Hahn SH, Ahn YM, Jang SH, Shin YJ, et al. Therapeutic trial in the first three Asian cases of ethylmalonic encephalopathy: response to riboflavin. J Inherit Metab Dis 2001;24:870-3.

153. Susin SA, Lorenzo HK, Zamzami N, Marzo I, Snow BE, et al. Molecular characterization of mitochondrial apoptosis-inducing factor. Nature 1999;397:441e6.

154. Joza N, Pospisilik JA, Hangen E, Hanada T, Modjtahedi N, et al. AIF: not just an apoptosis-inducing factor. Ann NY Acad Sci 2009;1171:2-11.

155. Ghezzi D, Sevrioukova I, Invernizzi F, Lamperti C, Mora M, et al. Severe X-linked mitochondrial encephalomyopathy associated with a mutation in apoptosis-inducing factor. Am J Hum Genet 2010;86:639-49.

156. Berger I, Ben-Neriah Z, Dor-Wolman T, Shaag A, Saada A, et al. Early prenatal ventriculomegaly due to an aifm1 mutation identified by linkage analysis and whole exome sequencing. Mol Genet Metab 2011;104:517-20.

157. Rinaldi C, Grunseich C, Sevrioukova IF, Schindler A, Horkayne-Szakaly I, et al. Cowchock syndrome is associated with a mutation in apoptosis-inducing factor. Am J Hum Genet 2012;91:1095-102.

158. Zong L, Guan J, Ealy M, Zhang Q, Wang D, et al. Mutations in apoptosis-inducing factor cause x-linked recessive auditory neuropathy spectrum disorder. J Med Genet 2015;52:523-31.

159. Mierzewska H, Rydzanicz M, Bieganski T, Kosinska J, Mierzewska-Schmidt M, et al. Spondyloepimetaphyseal dysplasia with neurodegeneration associated with aifm1 mutation - a novel phenotype of the mitochondrial disease. Clin Genet 2017;91:30-7.

160. Heimer G, Eyal E, Zhu X, Ruzzo EK, Marek-Yagel D, et al. Mutations in AIFM1 cause an X-linked childhood cerebellar ataxia partially responsive to riboflavin. Eur J Paediatr Neurol 2018;22:93-101.

Journal of Translational Genetics and Genomics
ISSN 2578-5281 (Online)
Follow Us

Portico

All published articles are preserved here permanently:

https://www.portico.org/publishers/oae/

Portico

All published articles are preserved here permanently:

https://www.portico.org/publishers/oae/