Molecular and biochemical investigations of inborn errors of metabolism-altered redox homeostasis in branched-chain amino acid disorders, organic acidurias, and homocystinuria

References

• Agana M, Frueh J, Kamboj M, et al. Common metabolic disorder (inborn errors of metabolism) concerns in primary care practice. Ann Transl Med. 2018;6(24):469.
   PubMed Web of Science ®Google Scholar
• Kumar A, Palfrey HA, Pathak R, et al. The metabolism and significance of homocysteine in nutrition and health. Nutr Metab. 2017;14:78.
   Google Scholar
• Sandlers Y. Amino acids profiling for the diagnosis of metabolic disorders. Chemistry Faculty Publications (IntechOpen). 2019;552. https://engagedscholarship.csuohio.edu/scichem_facpub/552
   Google Scholar
• Gilbert-Barness E, Farrell PM. Approach to diagnosis of metabolic diseases. TRD. 2016;1(1):3–22.
   Google Scholar
• Ferreira CR, van Karnebeek CDM. Inborn errors of metabolism. Handb Clin Neurol. 2019;162:449–481.
   PubMedGoogle Scholar
• Richard E, Gallego-Villar L, Rivera-Barahona A, Oyarzábal A, et al. Altered redox homeostasis in branched-chain amino acid disorders, organic acidurias, and homocystinuria. Oxid Med Cell Longev. 2018;2018:1246069.
   PubMed Web of Science ®Google Scholar
• Kurutas EB. The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: current state. Nutr J. 2016; 15(1):71.
   PubMed Web of Science ®Google Scholar
• He L, He T, Farrar S, et al. Antioxidants maintain cellular redox homeostasis by elimination of reactive oxygen species. Cell Physiol Biochem. 2017;44(2):532–553.
   PubMedGoogle Scholar
• Mc Guire PJ, Parikh A, Diaz GA. Profiling of oxidative stress in patients with inborn errors of metabolism. Mol Genet Metab. 2009;98(1–2):173–180.
   PubMed Web of Science ®Google Scholar
• Ribas GS, Biancini GB, Mescka C, et al. Oxidative stress parameters in urine from patients with disorders of propionate metabolism: a beneficial effect of L:-carnitine supplementation. Cell Mol Neurobiol. 2012;32(1):77–82.
   PubMed Web of Science ®Google Scholar
• Ballatori N, Krance SM, Notenboom S, et al. Glutathione dysregulation and the etiology and progression of human diseases. Biol Chem. 2009;390(3):191–214.
   PubMed Web of Science ®Google Scholar
• Salmi H, Leonard JV, Lapatto R. Patients with organic acidaemias have an altered thiol status. Acta Paediatr. 2012;101(11):e505–e508.
   PubMed Web of Science ®Google Scholar
• Pastore A, Martinelli D, Piemonte F, et al. Glutathione metabolism in cobalamin deficiency type C (cblC). J Inherit Metab Dis. 2014;37(1):125–129.
   PubMed Web of Science ®Google Scholar
• Atkuri KR, Cowan TM, Kwan T, et al. Inherited disorders affecting mitochondrial function are associated with glutathione deficiency and hypocitrullinemia. Proc Natl Acad Sci USA. 2009;106(10):3941–3945.
   PubMed Web of Science ®Google Scholar
• Milkovic L, Cipak Gasparovic A, Cindric M, et al. Short overview of ROS as cell function regulators and their implications in therapy concepts. Cells. 2019;8(8):793.
   PubMed Web of Science ®Google Scholar
• Willems Peter HGM, Rossignol R, Dieteren CEJ, et al. Redox homeostasis and mitochondrial dynamics. Cell Metab. 2015;22(2):207–212.
   PubMed Web of Science ®Google Scholar
• Olsen RKJ, Cornelius N, Gregersen N. Redox signalling and mitochondrial stress responses; lessons from inborn errors of metabolism. J Inherit Metab Dis. 2015;38(4):703–719.
   PubMed Web of Science ®Google Scholar
• Stark Z, Tan TY, Chong B, et al. A prospective evaluation of whole-exome sequencing as a first-tier molecular test in infants with suspected monogenic disorders. Genet Med. 2016;18:1090–1096.
   PubMed Web of Science ®Google Scholar
• Yang Y, Wang L, Wang B, et al. Application of next-generation sequencing following tandem mass spectrometry to expand newborn screening for inborn errors of metabolism: a multicenter study. Front Genet. 2019;10:86.
   PubMed Web of Science ®Google Scholar
• Civallero G, de Kremer R, Giugliani R. High-risk screening and diagnosis of inborn errors of metabolism: a practical guide for laboratories. J Inborn Error Metab Screen. 2018;6:1–6.
   Google Scholar
• Lee JJY, Wasserman WW, Hoffmann GF, et al. Knowledge base and mini-expert platform for the diagnosis of inborn errors of metabolism. Genet Med. 2018;20(1):151–158.
   PubMed Web of Science ®Google Scholar
• Stenton SL, Kremer LS, Kopajtich R, et al. The diagnosis of inborn errors of metabolism by an integrative "multi-omics" approach: a perspective encompassing genomics, transcriptomics, and proteomics. J Inher Metab Dis. 2020;43(1):25–35.
   PubMed Web of Science ®Google Scholar
• El-Hattab AW. Inborn errors of metabolism. Clin Perinatol. 2015;42(2):413–439.
   PubMed Web of Science ®Google Scholar
• Altimimi HA, Aljawadi HF, Ali EA. Inborn errors of metabolism in children with unexplained developmental delay in Misan, Iraq. Oman Med J. 2019;34(4):297–301.
   PubMedGoogle Scholar
• Raghuveer TS, Garg U, Graf WD. Inborn errors of metabolism in infancy and early childhood: an update. Am Fam Phys. 2006;73(11):1981–1990.
   PubMed Web of Science ®Google Scholar
• Biffi A. Hematopoietic stem cell gene therapy for storage disease: current and new indications. Mol Ther. 2017;25(5):1155–1162.
   PubMed Web of Science ®Google Scholar
• Yue WW, Mackinnon S, Bezerra GA. Substrate reduction therapy for inborn errors of metabolism. Emerg Top Life Sci. 2019;3(1):63–73.
   PubMedGoogle Scholar
• Forrester SJ, Kikuchi DS, Hernandes MS, et al. Reactive oxygen species in metabolic and inflammatory signaling. Circ Res. 2018;122(6):877–902.
   PubMed Web of Science ®Google Scholar
• Finkel T. Signal transduction by mitochondrial oxidants. J Biol Chem. 2012; 287(7):4434–4440.
   PubMed Web of Science ®Google Scholar
• Sobotta MC, Liou W, Stöcker S, et al. Peroxiredoxin-2 and STAT3 form a redox relay for H2O2 signaling. Nat Chem Biol. 2015;11(1):64–70.
   PubMed Web of Science ®Google Scholar
• Yin F, Sancheti H, Liu Z, et al. Mitochondrial function in ageing: coordination with signalling and transcriptional pathways. J Physiol. 2016;594(8):2025–2042.
   PubMed Web of Science ®Google Scholar
• AuchèRe F, Rusnak F. What is the ultimate fate of superoxide anion in vivo? J Biol Inorg Chem. 2002;7:664–667.
   PubMed Web of Science ®Google Scholar
• Ng CF, Schafer FQ, Buettner GR, et al. The rate of cellular hydrogen peroxide removal shows dependency on GSH: mathematical insight into in vivo H2O2 and GPx concentrations. Free Radic Res. 2007;41(11):1201–1211.
   PubMed Web of Science ®Google Scholar
• Kaludercic N, Di Lisa F. Mitochondrial ROS formation in the pathogenesis of diabetic cardiomyopathy. Front Cardiovasc Med. 2020;7:12.
   PubMed Web of Science ®Google Scholar
• Wu H, Wei H, Sehgal SA, et al. Mitophagy receptors sense stress signals and couple mitochondrial dynamic machinery for mitochondrial quality control. Free Radic Biol Med. 2016;100:199–209.
   PubMed Web of Science ®Google Scholar
• Boneh A. Signal transduction in inherited metabolic disorders: a model for a possible pathogenetic mechanism. J Inherit Metab Dis. 2015;38(4):729–740.
   PubMed Web of Science ®Google Scholar
• Alcaide P, Merinero B, Ruiz-Sala P, et al. Defining the pathogenicity of creatinine deficiency syndrome. Hum Mutat. 2011;32(3):282–291.
   PubMed Web of Science ®Google Scholar
• Gallego-Villar L, Perez-Cerda C, Perez B, et al. Functional characterization of novel genotypes and cellular oxidative stress studies in propionic acidemia. J Inherit Metab Dis. 2013;36(5):731–740.
   PubMed Web of Science ®Google Scholar
• Richard E, Alvarez-Barrientos A, Perez B, et al. Methylmalonic acidaemia leads to increased production of reactive oxygen species and induction of apoptosis through the mitochondrial/caspase pathway. J Pathol. 2007;213(4):453–461.
   PubMed Web of Science ®Google Scholar
• Richard E, Desviat LR, Ugarte M, et al. Oxidative stress and apoptosis in homocystinuria patients with genetic remethylation defects. J Cell Biochem. 2013;114(1):183–191.
   PubMed Web of Science ®Google Scholar
• Trempolec N, Muñoz JP, Slobodnyuk K, et al. Induction of oxidative metabolism by the p38α/MK2 pathway. Sci Rep. 2017;7(1):11367.
   PubMed Web of Science ®Google Scholar
• Escós A, Risco A, Alsina-Beauchamp D, et al. p38γ and p38δ mitogen activated protein kinases (MAPKs), new stars in the MAPK galaxy. Front Cell Dev Biol. 2016;4:31.
   PubMed Web of Science ®Google Scholar
• Zarubin T, Han J. Activation and signaling of the p38 MAP kinase pathway. Cell Res. 2005;15(1):11–18.
   PubMed Web of Science ®Google Scholar
• Papa S, Choy PM, Bubici C. The ERK and JNK pathways in the regulation of metabolic reprogramming. Oncogene. 2019;38(13):2223–2240.
   PubMed Web of Science ®Google Scholar
• Bogoyevitch MA, Kobe B. Uses for JNK: the many and varied substrates of the c-Jun N-terminal kinases. Microbiol Mol Biol Rev. 2006;70(4):1061–1095.
   PubMed Web of Science ®Google Scholar
• Chen L, Deng H, Cui H, et al. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget. 2018;9(6):7204–7218.
   PubMedGoogle Scholar
• Wang C, Youle RJ. The role of mitochondria in apoptosis*. Annu Rev Genet. 2009;43:95–118.
   PubMed Web of Science ®Google Scholar
• Hinchy EC, Gruszczyk AV, Willows R, et al. Mitochondria-derived ROS activate AMP-activated protein kinase (AMPK) indirectly. J Biol Chem. 2018;293(44):17208–17217.
   PubMed Web of Science ®Google Scholar
• Saxton RA, Sabatini DM. mTOR Signaling in Growth, Metabolism, and Disease. Cell. 2017;168(6):960–976.
   PubMed Web of Science ®Google Scholar
• Thomas LW, Ashcroft M. Exploring the molecular interface between hypoxia-inducible factor signalling and mitochondria. Cell Mol Life Sci. 2019;76(9):1759–1777.
   PubMed Web of Science ®Google Scholar
• Jacobsen DW, Hannibal L. Redox signaling in inherited diseases of metabolism. Curr Opin Physiol. 2019;9:48–55.
   Web of Science ®Google Scholar
• Rivera-Barahona A, Alonso-Barroso E, Perez B, et al. Treatment with antioxidants ameliorates oxidative damage in a mouse model of propionic acidemia. Mol Genet Metab. 2017;122(1–2):43–50.
   PubMed Web of Science ®Google Scholar
• Gallego-Villar L, Perez B, Ugarte M, et al. Antioxidants successfully reduce ROS production in propionic acidemia fibroblasts. Biochem Biophys Res Commun. 2014;452(3):457–461.
   PubMed Web of Science ®Google Scholar
• Lopez-Erauskin J, Fourcade S, Galino J, et al. Antioxidants halt axonal degeneration in a mouse model of X-adrenoleukodystrophy. Ann Neurol. 2011;70(1):84–92.
   PubMed Web of Science ®Google Scholar
• Ribas GS, Vargas CR, Wajner M. L-carnitine supplementation as a potential antioxidant therapy for inherited neurometabolic disorders. Gene. 2014;533(2):469–476.
   PubMed Web of Science ®Google Scholar
• Sharma LK, Fang H, Liu J, et al. Mitochondrial respiratory complex I dysfunction promotes tumorigenesis through ROS alteration and AKT activation. Hum Mol Genet. 2011;20(23):4605–4616.
   PubMed Web of Science ®Google Scholar
• Guo J, Lemire BD. The ubiquinone-binding site of the Saccharomyces cerevisiae succinate-ubiquinone oxidoreductase is a source of superoxide. J Biol Chem. 2003;278(48):47629–47635.
   PubMed Web of Science ®Google Scholar
• Huang J, Lemire BD. Mutations in the C. elegans succinate dehydrogenase iron-sulfur subunit promote superoxide generation and premature aging. J Mol Biol. 2009;387(3):559–569.
   PubMed Web of Science ®Google Scholar
• Phaniendra A, Jestadi DB, Periyasamy L. Free radicals: properties, sources, targets, and their implication in various diseases. Indian J Clin Biochem. 2015;30(1):11–26.
   PubMed Web of Science ®Google Scholar
• Smeitink J, van den Heuvel L, DiMauro S. The genetics and pathology of oxidative phosphorylation. Nat Rev Genet. 2001;2(5):342–352.
   PubMed Web of Science ®Google Scholar
• Kolker S, Burgard P, Sauer SW, et al. Current concepts in organic acidurias: understanding intra- and extracerebral disease manifestation. J Inherit Metab Dis. 2013;36(4):635–644.
   PubMed Web of Science ®Google Scholar
• Schapira AH. Mitochondrial disease. Lancet. 2006;368(9529):70–82.
   PubMed Web of Science ®Google Scholar
• Wajner M, Goodman SI. Disruption of mitochondrial homeostasis in organic acidurias: insights from human and animal studies. J Bioenerg Biomembr. 2011;43(1):31–38.
   PubMed Web of Science ®Google Scholar
• 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(7):e69282.
   PubMed Web of Science ®Google Scholar
• Han JM, Jeong SJ, Park MC, et al. Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway. Cell. 2012;149(2):410–424.
   PubMed Web of Science ®Google Scholar
• Anderson KA, Huynh FK, Fisher-Wellman K, et al. SIRT4 is a lysine deacylase that controls leucine metabolism and insulin secretion. Cell Metab. 2017;25(4):838–855.
   PubMed Web of Science ®Google Scholar
• Holeček M. Branched-chain amino acids in health and disease: metabolism, alterations in blood plasma, and as supplements. Nutr Metab. 2018;15:33.
   Google Scholar
• Garcia-Cazorla A, Oyarzabal A, J, Fort J, et al. Two novel mutations in the BCKDK (branched-chain keto-acid dehydrogenase kinase) gene are responsible for a neurobehavioral deficit in two pediatric unrelated patients. Hum Mutat. 2014;35(4):470–477.
   PubMed Web of Science ®Google Scholar
• Novarino G, El-Fishawy P, Kayserili H, et al. Mutations in BCKD-kinase lead to a potentially treatable form of autism with epilepsy. Science. 2012;338(6105):394–397.
   PubMed Web of Science ®Google Scholar
• Villani GRD, Gallo G, Scolamiero E, et al. "Classical organic acidurias": diagnosis and pathogenesis. Clin Exp Med. 2017;17(3):305–323.
   PubMed Web of Science ®Google Scholar
• Richard E, Rodriguez-Pombo P, Desviat LR, et al. Mitochondrial organic acidurias. Part II: mitochondrial dysfunction. In Palau F, Cadenas S, editors. Mitochondrial pathophysiology. Kerala, India: Research Signpost; 2011. p. 173–191.
   Google Scholar
• Oyarzabal A, Martinez-Pardo M, Merinero B, et al. A novel regulatory defect in the branched-chain α-keto acid dehydrogenase complex due to a mutation in the PPM1K gene causes a mild variant phenotype of maple syrup urine disease. Hum Mutat. 2013;34(2):355–362.
   PubMed Web of Science ®Google Scholar
• Grünert SC, Müllerleile S, De Silva L, et al. Propionic acidemia: clinical course and outcome in 55 pediatric and adolescent patients. Orphanet J Rare Dis. 2013;8(1):6.
   PubMed Web of Science ®Google Scholar
• Kölker S, Valayannopoulos V, Burlina AB, et al. The phenotypic spectrum of organic acidurias and urea cycle disorders. Part 2: the evolving clinical phenotype. J Inherit Metab Dis. 2015;38(6):1059–1074.
   PubMed Web of Science ®Google Scholar
• Keyfi F, Talebi S, Varasteh AR. Methylmalonic acidemia diagnosis by laboratory methods. Rep Biochem Mol Biol. 2016;5(1):1–14.
   PubMed Web of Science ®Google Scholar
• Almási T, Guey LT, Lukacs C, et al. Systematic literature review and meta-analysis on the epidemiology of methylmalonic acidemia (MMA) with a focus on MMA caused by methylmalonyl-CoA mutase (mut) deficiency. Orphanet J Rare Dis. 2019;14(1):84.
   PubMed Web of Science ®Google Scholar
• Stepien KM, Heaton R, Rankin S, et al. Evidence of Oxidative Stress and Secondary Mitochondrial Dysfunction in Metabolic and Non-Metabolic Disorders. JCM. 2017;6(7):71.
   Web of Science ®Google Scholar
• Pettenuzzo LF, Ferreira G. d C, Schmidt AL, et al. Differential inhibitory effects of methylmalonic acid on respiratory chain complex activities in rat tissues. Int J Dev Neurosci. 2006; 24(1):45–52.
   PubMed Web of Science ®Google Scholar
• Luciani A, Devuyst O. Methylmalonyl acidemia: from mitochondrial metabolism to defective mitophagy and disease. Autophagy. 2020;16(6):1159–1161.
   PubMed Web of Science ®Google Scholar
• Mirandola SR, Melo DR, Schuck PF, et al. Methylmalonate inhibits succinate-supported oxygen consumption by interfering with mitochondrial succinate uptake. J Inherit Metab Dis. 2008;31(1):44–54.
   PubMed Web of Science ®Google Scholar
• Goodman S, Frerman F. Organic acidemias due to defects in lysine oxidation: 2-ketoadipic acidemia and glutaric acidemia. In Scriver CR, Beaudet AL, Sly WS, Valle D, editors. The metabolic and molecular basis of inherited disease. New York: McGraw-Hill Inc.; 2001. p. 2195–2204.
   Google Scholar
• Strauss KA, Puffenberger EG, Robinson DL, et al. Type I glutaric aciduria, part 1: natural history of 77 patients. Am J Med Genet C Semin Med Genet. 2003;121C(1):38–52.
   PubMed Web of Science ®Google Scholar
• Kaplan P, Tatarkova Z, Sivonova MK, et al. Homocysteine and mitochondria in cardiovascular and cerebrovascular systems. IJMS. 2020;21(20):7698.
   Web of Science ®Google Scholar
• Jacobsen DW. Hyperhomocysteinemia and oxidative stress: time for a reality check? Arterioscler Thromb Vasc Biol. 2000;20(5):1182–1184.
   PubMed Web of Science ®Google Scholar
• Zou CG, Banerjee R. Homocysteine and redox signaling. Antioxid Redox Signal. 2005;7(5–6):547–559.
   PubMed Web of Science ®Google Scholar
• Mudd SH, Levy HL, Kraus JP. Disorders of transsulfuration. In Kinzler K, Ballabio A, Antonarakis SE, Beaudet AL, Vogelstein B, Valle D, editors. The online metabolic and molecular bases of inherited diseases. New York: McGrall-Hill; 2011.
   Google Scholar
• Schiff M, Blom HJ. Treatment of inherited homocystinurias. Neuropediatrics. 2012;43(6):295–304.
   PubMed Web of Science ®Google Scholar
• Zuhra K, Augsburger F, Majtan T, et al. Cystathionine-β-synthase: molecular regulation and pharmacological inhibition. Biomolecules. 2020;10(5):697.
   Web of Science ®Google Scholar
• Faverzani JL, Hammerschmidt TG, Sitta A, et al. Oxidative stress in homocystinuria due to cystathionine ß-synthase deficiency: findings in patients and in animal models. Cell Mol Neurobiol. 2017;37(8):1477–1485.
   PubMed Web of Science ®Google Scholar
• Hoss GRW, Poloni S, Blom HJ, et al. Three main causes of homocystinuria: CBS, cblC and MTHFR deficiency. What do they have in common? J Inborn Errors Metab Screen. 2019;7:e20190007.
   Google Scholar
• Richard E, Brasil S, Leal F, et al. Isolated and combined remethylation disorders: biochemical and genetic diagnosis and pathophysiology. J Inborn Errors Metab Screen. 2017;5:1–11.
   Google Scholar
• Urv TK, Parisi MA. Newborn screening: beyond the spot. Adv Exp Med Biol. 2017;1031:323–346.
   PubMed Web of Science ®Google Scholar
• Berry SA. Newborn screening. Clin Perinatol. 2015;42(2):441–453.
   PubMed Web of Science ®Google Scholar
• Blau N, Duran M, Gibson KM. Laboratory guide to the methods in biochemical genetics. Berlin/Heidelberg, Germany: Springer; 2008.
   Google Scholar
• Liu YJ, McIntyre RL, Janssens GE, et al. Mitochondrial fission and fusion: a dynamic role in aging and potential target for age-related disease. Mech Ageing Dev. 2020;186:111212.
   PubMed Web of Science ®Google Scholar
• Youle RJ, van der Bliek AM. Mitochondrial fission, fusion, and stress. Science. 2012;337(6098):1062–1065.
   PubMed Web of Science ®Google Scholar
• Pieczenik SR, Neustadt J. Mitochondrial dysfunction and molecular pathways of disease. Exp Mol Pathol. 2007;83(1):84–92.
   PubMed Web of Science ®Google Scholar
• Mailloux RJ. An update on mitochondrial reactive oxygen species production. Antioxidants. 2020; 9(6):472.
   Web of Science ®Google Scholar
• Hu F, Liu F. Mitochondrial stress: a bridge between mitochondrial dysfunction and metabolic diseases? Cell Signal. 2011;23(10):1528–1533.
   PubMed Web of Science ®Google Scholar
• Valera-Alberni M, Canto C. Mitochondrial stress management: a dynamic journey. Cell Stress. 2018; 2(10):253–274.
   PubMed Web of Science ®Google Scholar
• He Q, Harris N, Ren J, et al. Mitochondria-targeted antioxidant prevents cardiac dysfunction induced by tafazzin gene knockdown in cardiac myocytes. Oxid Med Cell Longev. 2014;2014:654198.
   PubMed Web of Science ®Google Scholar
• Mailloux RJ. Application of mitochondria-targeted pharmaceuticals for the treatment of heart disease. Curr Pharm Des. 2016;22(31):4763–4779.
   PubMed Web of Science ®Google Scholar
• Ni R, Cao T, Xiong S, et al. Therapeutic inhibition of mitochondrial reactive oxygen species with mito-TEMPO reduces diabetic cardiomyopathy. Free Radic Biol Med. 2016;90:12–23.
   PubMed Web of Science ®Google Scholar
• Wang W, Karamanlidis G, Tian R. Novel targets for mitochondrial medicine. Sci Transl Med. 2016;8(326):326rv3.
   PubMed Web of Science ®Google Scholar
• Ubah OC, Wallace HM. Cancer therapy: Targeting mitochondria and other sub-cellular organelles. Curr Pharm Des. 2014;20(2):201–222.
   PubMed Web of Science ®Google Scholar
• García-García J, Monistrol-Mula A, Cardellach F, et al. Nutrition, bioenergetics, and metabolic syndrome. Nutrients. 2020;12(9):2785.
   Web of Science ®Google Scholar
• Weinberg SE, Chandel NS. Targeting mitochondria metabolism for cancer therapy. Nat Chem Biol. 2015;11(1):9–15.
   PubMed Web of Science ®Google Scholar
• Patergnani S, Missiroli S, Marchi S, et al. Mitochondria-associated endoplasmic reticulum membranes microenvironment: targeting autophagic and apoptotic pathways in cancer therapy. Front Oncol. 2015;5:173.
   PubMed Web of Science ®Google Scholar
• Reddy PH. Inhibitors of mitochondrial fission as a therapeutic strategy for diseases with oxidative stress and mitochondrial dysfunction. J Alzheimers Dis. 2014;40(2):245–256.
   PubMed Web of Science ®Google Scholar
• Tachibana M, Amato P, Sparman M, et al. Towards germline gene therapy of inherited mitochondrial diseases. Nature. 2013;493(7434):627–631.
   PubMed Web of Science ®Google Scholar
• Craven L, Tuppen HA, Greggains GD, et al. Pronuclear transfer in human embryos to prevent transmission of mitochondrial DNA disease. Nature. 2010;465(7294):82–85.
   PubMed Web of Science ®Google Scholar
• Paull D, Emmanuele V, Weiss KA, et al. Nuclear genome transfer in human oocytes eliminates mitochondrial DNA variants. Nature. 2013;493(7434):632–637.
   PubMed Web of Science ®Google Scholar
• Harthan AA. An introduction to pharmacotherapy for inborn errors of metabolism. J Pediatr Pharmacol Ther. 2018;23(6):432–446.
   PubMedGoogle Scholar
• Strauss KA, Wardley B, Robinson D, et al. Classical maple syrup urine disease and brain development: principles of management and formula design. Mol Genet Metab. 2010;99(4):333–345.
   PubMed Web of Science ®Google Scholar
• Peña-Quintana L, Llarena M, Reyes- Suárez D, et al. Profile of sodium phenylbutyrate granules for the treatment of urea-cycle disorders: patient perspectives. Patient Prefer Adherence. 2017;11:1489–1496.
   PubMed Web of Science ®Google Scholar
• Häberle J, Boddaert N, Burlina A, et al. Suggested guidelines for the diagnosis and management of urea cycle disorders. Orphanet J Rare Dis. 2012;7:32. h]
   PubMed Web of Science ®Google Scholar
• Masurel-Paulet A, Poggi-Bach J, Rolland M-O, et al. NTBC treatment in tyrosinaemia type I: long-term outcome in French patients. J Inherit Metab Dis. 2008;31(1):81–87.
   PubMed Web of Science ®Google Scholar
• Priestley JRC, Alharbi H, Callahan KP, et al. The importance of succinylacetone: tyrosinemia type I presenting with hyperinsulinism and multiorgan failure following normal newborn screening. IJNS. 2020;6(2):39.
   Web of Science ®Google Scholar
• Christ SE, Moffitt AJ, Peck D, et al. The effects of tetrahydrobiopterin (BH4) treatment on brain function in individuals with phenylketonuria. Neuroimage Clin. 2013;3:539–547.
   PubMed Web of Science ®Google Scholar
• van Vliet D, Anjema K, Jahja R, et al. BH4 treatment in BH4-responsive PKU patients: preliminary data on blood prolactin concentrations suggest increased cerebral dopamine concentrations. Mol Genet Metab. 2015;114(1):29–33.
   PubMed Web of Science ®Google Scholar
• Ogier de Baulny H, Gérard M, Saudubray JM, et al. Remethylation defects: guidelines for clinical diagnosis and treatment. Eur J Pediatr. 1998;157(S2):S77–S83.
   PubMed Web of Science ®Google Scholar
• Morris AAM, Kožich V, Santra S, et al. Guidelines for the diagnosis and management of cystathionine beta-synthase deficiency. J Inherit Metab Dis. 2017;40(1):49–74.
   PubMed Web of Science ®Google Scholar
• Schmidt HHHW, Stocker R, Vollbracht C, et al. Antioxidants in translational medicine. Antioxid Redox Signal. 2015;23(14):1130–1143.
   PubMed Web of Science ®Google Scholar
• Forman HJ, Davies KJA, Ursini F. How do nutritional antioxidants really work: nucleophilic tone and para-hormesis versus free radical scavenging in vivo. Free Radic Biol Med. 2014;66:24–35.
   PubMed Web of Science ®Google Scholar
• Strauss KA, Williams KB, Carson VJ, et al. Glutaric acidemia type 1: Treatment and outcome of 168 patients over three decades. Mol Genet Metab. 2020;131(3):325–340.
   PubMed Web of Science ®Google Scholar
• Guerreiro G, Mescka CP, Sitta A, et al. Urinary biomarkers of oxidative damage in maple syrup urine disease: the L-carnitine role. Int J Dev Neurosci. 2015;42:10–14.
   PubMed Web of Science ®Google Scholar
• Kumru B, Oztürk Hismi B. Investigation of L-carnitine concentrations in treated patients with maple syrup urine disease. J Pediatr Genet. 2019;8(3):133–136.
   PubMed Web of Science ®Google Scholar