Scientific Papers

New insights into the nutritional genomics of adult-onset riboflavin-responsive diseases | Nutrition & Metabolism


  • LeBlanc JG, Milani C, de Giori GS, Sesma F, van Sinderen D, Ventura M. Bacteria as vitamin suppliers to their host: a gut microbiota perspective. Curr Opin Biotechnol. 2013;24:160–8.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Powers HJ. Riboflavin (vitamin B-2) and health. Am J Clin Nutr. 2003;77:1352–60.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • NRV NRVfAaNZ-: Riboflavin. 2005.

  • Subramanian VS, Sabui S, Teafatiller T, Bohl JA, Said HM. Structure/functional aspects of the human riboflavin transporter-3 (SLC52A3): role of the predicted glycosylation and substrate-interacting sites. Am J Physiol Cell Physiol. 2017;313:C228–38.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

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

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

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

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Chiong MA, Sim KG, Carpenter K, Rhead W, Ho G, Olsen RK, Christodoulou J. Transient multiple acyl-CoA dehydrogenation deficiency in a newborn female caused by maternal riboflavin deficiency. Mol Genet Metab. 2007;92:109–14.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Liu Z, Peng Q, Li J, Rao C, Lu X. BVVLS2 overlooked for 3 years in a pediatric patient caused by novel compound heterozygous mutations in SLC52A2 gene. Clin Chim Acta. 2021;523:402–6.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Australian Health Survey: Usual Nutrient Intakes [ http://www.nrv.gov.au/nutrients/riboflavin]

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

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Anderson JJ, Suchindran CM, Roggenkamp KJ. Micronutrient intakes in two US populations of older adults: lipid research clinics program prevalence study findings. J Nutr Health Aging. 2009;13:595–600.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Powers HJ, Hill MH, Mushtaq S, Dainty JR, Majsak-Newman G, Williams EA. Correcting a marginal riboflavin deficiency improves hematologic status in young women in the United Kingdom (RIBOFEM). Am J Clin Nutr. 2011;93:1274–84.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Australian Bureau of Statistics -, 2014, Australian Health Survey: Nutrition First Results – Foods and Nutrients, 2011–12 [https://www.abs.gov.au/statistics/health/health-conditions-and-risks/australian-health-survey-usual-nutrient-intakes/latest-release#vitamins]

  • Mosegaard S, Dipace G, Bross P, Carlsen J, Gregersen N, Olsen RKJ. Riboflavin deficiency—implications for general human health and inborn errors of metabolism. Int J Mol Sci. 2020;21(11):3847.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Murgia C, Adamski MM. Translation of nutritional genomics into nutrition practice: the next step. Nutrients. 2017;9(4):366.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 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.

    Article 
    PubMed 

    Google Scholar
     

  • Mosegaard S, Bruun GH, Flyvbjerg KF, Bliksrud YT, Gregersen N, Dembic M, Annexstad E, Tangeraas T, Olsen RKJ, Andresen BS. An intronic variation in SLC52A1 causes exon skipping and transient riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency. Mol Genet Metab. 2017;122:182–8.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ho G, Yonezawa A, Masuda S, Inui K, Sim KG, Carpenter K, Olsen RK, Mitchell JJ, Rhead WJ, Peters G, Christodoulou J. 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:E1976-1984.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Vir SC, Love AH, Thompson W. Riboflavin status during pregnancy. Am J Clin Nutr. 1981;34:2699–705.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Bosch AM, Abeling NG, Ijlst L, Knoester H, van der Pol WL, Stroomer AE, Wanders RJ, Visser G, Wijburg FA, Duran M, Waterham HR. 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.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Bosch AM, Stroek K, Abeling NG, Waterham HR, Ijlst L, Wanders RJ. The Brown-Vialetto-Van Laere and Fazio Londe syndrome revisited: natural history, genetics, treatment and future perspectives. Orphanet J Rare Dis. 2012;7:83.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Carreau C, Lenglet T, Mosnier I, Lahlou G, Fargeot G, Weiss N, Demeret S, Salachas F, Veauville-Merllie A, Acquaviva C, Nadjar Y. A juvenile ALS-like phenotype dramatically improved after high-dose riboflavin treatment. Ann Clin Transl Neurol. 2020;7:250–3.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Foley AR, Menezes MP, Pandraud A, Gonzalez MA, Al-Odaib A, Abrams AJ, Sugano K, Yonezawa A, Manzur AY, Burns J, et al. Treatable childhood neuronopathy caused by mutations in riboflavin transporter RFVT2. Brain. 2014;137:44–56.

    Article 
    PubMed 

    Google Scholar
     

  • Carreau C, Benoit C, Ahle G, Cauquil C, Roubertie A, Lenglet T, Cosgrove J, Meunier I, Veauville-Merllié A, Acquaviva-Bourdain C, Nadjar Y. Late-onset riboflavin transporter deficiency: a treatable mimic of various motor neuropathy aetiologies. J Neurol Neurosurg Psychiatry. 2021;92(1):27–35.

    Article 

    Google Scholar
     

  • Cosgrove J, Datta S, Busby M. Adult onset Brown–Vialetto–Van Laere syndrome with opsoclonus and a novel heterozygous mutation: a case report. Clin Neurol Neurosurg. 2015;128:1–3.

    Article 
    PubMed 

    Google Scholar
     

  • Camargos S, Guerreiro R, Bras J, Mageste LS. Late-onset and acute presentation of Brown–Vialetto–Van Laere syndrome in a Brazilian family. Neurol Genet. 2018;4:e215.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Udhayabanu T, Subramanian VS, Teafatiller T, Gowda VK, Raghavan VS, Varalakshmi P, Said HM, Ashokkumar B. SLC52A2 [p.P141T] and SLC52A3 [p.N21S] causing Brown–Vialetto–Van Laere syndrome in an indian patient: first genetically proven case with mutations in two riboflavin transporters. Clin Chim Acta. 2016;462:210–4.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bashford JA, Chowdhury FA, Shaw CE. Remarkable motor recovery after riboflavin therapy in adult-onset Brown–Vialetto–Van Laere syndrome. Pract Neurol. 2017;17:53–6.

    Article 
    PubMed 

    Google Scholar
     

  • Spaan AN, Ijlst L, van Roermund CW, Wijburg FA, Wanders RJ, Waterham HR. Identification of the human mitochondrial FAD transporter and its potential role in multiple acyl-CoA dehydrogenase deficiency. Mol Genet Metab. 2005;86:441–7.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Peng MZ, Shao YX, Li XZ, Zhang KD, Cai YN, Lin YT, Jiang MY, Liu ZC, Su XY, Zhang W, et al. Mitochondrial FAD shortage in SLC25A32 deficiency affects folate-mediated one-carbon metabolism. Cell Mol Life Sci. 2022;79:375.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Schiff M, Veauville-Merllie A, Su CH, Tzagoloff A, Rak M, Ogier de Baulny H, Boutron A, Smedts-Walters H, Romero NB, Rigal O, et al. SLC25A32 mutations and riboflavin-responsive exercise intolerance. N Engl J Med. 2016;374:795–7.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Al Shamsi B, Al Murshedi F, Al Habsi A, Al-Thihli K. Hypoketotic hypoglycemia without neuromuscular complications in patients with SLC25A32 deficiency. Eur J Hum Genet. 2022;30(8):976–9.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • 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.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Miccolis A, Galluccio M, Giancaspero TA, Indiveri C, Barile M. Bacterial over-expression and purification of the 3’phosphoadenosine 5’phosphosulfate (PAPS) reductase domain of human FAD synthase: functional characterization and homology modeling. Int J Mol Sci. 2012;13:16880–98.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Giancaspero TA, Galluccio M, Miccolis A, Leone P, Eberini I, Iametti S, Indiveri C, Barile M. Human FAD synthase is a bi-functional enzyme with a FAD hydrolase activity in the molybdopterin binding domain. Biochem Biophys Res Commun. 2015;465:443–9.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Olsen RKJ, Konarikova E, Giancaspero TA, Mosegaard S, Boczonadi V, Matakovic L, Veauville-Merllie A, Terrile C, Schwarzmayr T, Haack TB, 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.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Torchetti EM, Bonomi F, Galluccio M, Gianazza E, Giancaspero TA, Iametti S, Indiveri C, Barile M. Human FAD synthase (isoform 2): a component of the machinery that delivers FAD to apo-flavoproteins. FEBS J. 2011;278:4434–49.

    Article 
    PubMed 

    Google Scholar
     

  • Yazdanpanah B, Wiegmann K, Tchikov V, Krut O, Pongratz C, Schramm M, Kleinridders A, Wunderlich T, Kashkar H, Utermohlen O, et al. Riboflavin kinase couples TNF receptor 1 to NADPH oxidase. Nature. 2009;460:1159–63.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Auranen M, Paetau A, Piirila P, Pohju A, Salmi T, Lamminen A, Lofberg M, Mosegaard S, Olsen RK, Tyni T. Patient with multiple acyl-CoA dehydrogenation deficiency disease and FLAD1 mutations benefits from riboflavin therapy. Neuromuscul Disord. 2017;27:581–4.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Leulliot N, Blondeau K, Keller J, Ulryck N, Quevillon-Cheruel S, van Tilbeurgh H. Crystal structure of yeast FAD synthetase (Fad1) in complex with FAD. J Mol Biol. 2010;398:641–6.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Huerta C, Borek D, Machius M, Grishin NV, Zhang H. Structure and mechanism of a eukaryotic FMN adenylyltransferase. J Mol Biol. 2009;389:388–400.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Leone P, Galluccio M, Barbiroli A, Eberini I, Tolomeo M, Vrenna F, Gianazza E, Iametti S, Bonomi F, Indiveri C, Barile M. Bacterial production, characterization and protein modeling of a novel monofuctional isoform of FAD synthase in humans: an emergency protein? Molecules. 2018;23(1):116.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Leone P, Galluccio M, Quarta S, Anoz-Carbonell E, Medina M, Indiveri C, Barile M. Mutation of aspartate 238 in FAD synthase isoform 6 increases the specific activity by weakening the FAD binding. Int J Mol Sci. 2019;20(24):6203.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

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

    Article 
    CAS 
    PubMed 

    Google Scholar
     

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

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Mereis M, Wanders RJA, Schoonen M, Dercksen M, Smuts I, van der Westhuizen FH. Disorders of flavin adenine dinucleotide metabolism: MADD and related deficiencies. Int J Biochem Cell Biol. 2021;132:105899.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Chen W, Zhang Y, Ni Y, Cai S, Zheng X, Mastaglia FL, Wu J. Late-onset riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (MADD): case reports and epidemiology of ETFDH gene mutations. BMC Neurol. 2019;19:330.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Liang WC, Ohkuma A, Hayashi YK, Lopez LC, Hirano M, Nonaka I, Noguchi S, Chen LH, Jong YJ, Nishino I. ETFDH mutations, CoQ10 levels, and respiratory chain activities in patients with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency. Neuromuscul Disord. 2009;19:212–6.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhang J, Frerman FE, Kim JJ. Structure of electron transfer flavoprotein-ubiquinone oxidoreductase and electron transfer to the mitochondrial ubiquinone pool. Proc Natl Acad Sci U S A. 2006;103:16212–7.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Fan X, Xie B, Zou J, Luo J, Qin Z, D’Gama AM, Shi J, Yi S, Yang Q, Wang J, et al. Novel ETFDH mutations in four cases of riboflavin responsive multiple acyl-CoA dehydrogenase deficiency. Mol Genet Metab Rep. 2018;16:15–9.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Behin A, Acquaviva-Bourdain C, Souvannanorath S, Streichenberger N, Attarian S, Bassez G, Brivet M, Fouilhoux A, Labarre-Villa A, Laquerriere A, et al. Multiple acyl-CoA dehydrogenase deficiency (MADD) as a cause of late-onset treatable metabolic disease. Rev Neurol. 2016;172:231–41.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Macchione F, Salviati L, Bordugo A, Vincenzi M, Camilot M, Teofoli F, Pancheri E, Zordan R, Bertolin C, Rossi S, et al. Multiple acyl-COA dehydrogenase deficiency in elderly carriers. J Neurol. 2020;267:1414–9.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Missaglia S, Tavian D, Moro L, Angelini C. Characterization of two ETFDH mutations in a novel case of riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency. Lipids Health Dis. 2018;17:254.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cornelius N, Frerman FE, Corydon TJ, Palmfeldt J, Bross P, Gregersen N, Olsen RK. Molecular mechanisms of riboflavin responsiveness in patients with ETF-QO variations and multiple acyl-CoA dehydrogenation deficiency. Hum Mol Genet. 2012;21:3435–48.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wang ZQ, Chen XJ, Murong SX, Wang N, Wu ZY. Molecular analysis of 51 unrelated pedigrees with late-onset multiple acyl-CoA dehydrogenation deficiency (MADD) in southern China confirmed the most common ETFDH mutation and high carrier frequency of c.250G>A. J Mol Med. 2011;89:569–76.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Henriques BJ, Rodrigues JV, Olsen RK, Bross P, Gomes CM. Role of flavinylation in a mild variant of multiple acyl-CoA dehydrogenation deficiency: a molecular rationale for the effects of riboflavin supplementation. J Biol Chem. 2009;284:4222–9.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Nouws J, Nijtmans L, Houten SM, van den Brand M, Huynen M, Venselaar H, Hoefs S, Gloerich J, Kronick J, Hutchin T, et al. Acyl-CoA dehydrogenase 9 is required for the biogenesis of oxidative phosphorylation complex I. Cell Metab. 2010;12:283–94.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Scheffler IE. Assembling complex I with ACAD9. Cell Metab. 2010;12:211–2.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Repp BM, Mastantuono E, Alston CL, Schiff M, Haack TB, Rotig A, Ardissone A, Lombes A, Catarino CB, Diodato D, et al. Clinical, biochemical and genetic spectrum of 70 patients with ACAD9 deficiency: is riboflavin supplementation effective? Orphanet J Rare Dis. 2018;13:120.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • McAndrew RP, Wang Y, Mohsen AW, He M, Vockley J, Kim JJ. Structural basis for substrate fatty acyl chain specificity: crystal structure of human very-long-chain acyl-CoA dehydrogenase. J Biol Chem. 2008;283:9435–43.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dewulf JP, Barrea C, Vincent MF, De Laet C, Van Coster R, Seneca S, Marie S, Nassogne MC. Evidence of a wide spectrum of cardiac involvement due to ACAD9 mutations: report on nine patients. Mol Genet Metab. 2016;118:185–9.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Gueguen N, Piarroux J, Sarzi E, Benkirane M, Manes G, Delettre C, Amedro P, Leboucq N, Koenig M, Meyer P, et al. Optic neuropathy linked to ACAD9 pathogenic variants: a potentially riboflavin-responsive disorder? Mitochondrion. 2021;59:169–74.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Aintablian HK, Narayanan V, Belnap N, Ramsey K, Grebe TA. An atypical presentation of ACAD9 deficiency: diagnosis by whole exome sequencing broadens the phenotypic spectrum and alters treatment approach. Mol Genet Metab Rep. 2017;10:38–44.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Haack TB, Danhauser K, Haberberger B, Hoser J, Strecker V, Boehm D, Uziel G, Lamantea E, Invernizzi F, Poulton J, et al. Exome sequencing identifies ACAD9 mutations as a cause of complex I deficiency. Nat Genet. 2010;42:1131–4.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wilcken B, Bamforth F, Li Z, Zhu H, Ritvanen A, Renlund M, Stoll C, Alembik Y, Dott B, Czeizel AE, et al. Geographical and ethnic variation of the 677C>T allele of 5,10 methylenetetrahydrofolate reductase (MTHFR): findings from over 7000 newborns from 16 areas world wide. J Med Genet. 2003;40:619–25.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • dbSNP rs1801133 [https://www.ncbi.nlm.nih.gov/snp/rs1801133#variant_details]

  • Liew SC, Gupta ED. Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism: epidemiology, metabolism and the associated diseases. Eur J Med Genet. 2015;58:1–10.

    Article 
    PubMed 

    Google Scholar
     

  • Almekkawi AK, AlJardali MW, Daadaa HM, Lane AL, Worner AR, Karim MA, Scheck AC, Frye RE. Folate pathway gene single nucleotide polymorphisms and neural tube defects: a systematic review and meta-analysis. J Personal Med. 2022;12(10):1609.

    Article 

    Google Scholar
     

  • Liu F, Du J, Nie M, Fu J, Sun J. 5,10-methylenetetrahydrofolate reductase C677T gene polymorphism and peripheral arterial disease: A meta-analysis. Vascular. 2021;29:913–9.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Qin X, Spence JD, Li J, Zhang Y, Li Y, Sun N, Liang M, Song Y, Zhang Y, Wang B, et al. Interaction of serum vitamin B(12) and folate with MTHFR genotypes on risk of ischemic stroke. Neurology. 2020;94:e1126–36.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Clarke R, Halsey J, Bennett D, Lewington S. Homocysteine and vascular disease: review of published results of the homocysteine-lowering trials. J Inherit Metab Dis. 2011;34:83–91.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Froese DS, Kopec J, Rembeza E, Bezerra GA, Oberholzer AE, Suormala T, Lutz S, Chalk R, Borkowska O, Baumgartner MR, Yue WW. Structural basis for the regulation of human 5,10-methylenetetrahydrofolate reductase by phosphorylation and S-adenosylmethionine inhibition. Nat Commun. 2018;9:2261.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Guenther BD, Sheppard CA, Tran P, Rozen R, Matthews RG, Ludwig ML. The structure and properties of methylenetetrahydrofolate reductase from Escherichia coli suggest how folate ameliorates human hyperhomocysteinemia. Nat Struct Biol. 1999;6:359–65.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Pejchal R, Campbell E, Guenther BD, Lennon BW, Matthews RG, Ludwig ML. Structural perturbations in the Ala –> Val polymorphism of methylenetetrahydrofolate reductase: how binding of folates may protect against inactivation. Biochemistry. 2006;45:4808–18.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Yamada K, Chen Z, Rozen R, Matthews RG. Effects of common polymorphisms on the properties of recombinant human methylenetetrahydrofolate reductase. Proc Natl Acad Sci U S A. 2001;98:14853–8.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, Boers GJ, den Heijer M, Kluijtmans LA, van den Heuvel LP, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995;10:111–3.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Heux S, Morin F, Lea RA, Ovcaric M, Tajouri L, Griffiths LR. The methylentetrahydrofolate reductase gene variant (C677T) as a risk factor for essential hypertension in Caucasians. Hypertens Res. 2004;27:663–7.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Newton-Cheh C, Johnson T, Gateva V, Tobin MD, Bochud M, Coin L, Najjar SS, Zhao JH, Heath SC, Eyheramendy S, et al. Genome-wide association study identifies eight loci associated with blood pressure. Nat Genet. 2009;41:666–76.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Niu WQ, You YG, Qi Y. Strong association of methylenetetrahydrofolate reductase gene C677T polymorphism with hypertension and hypertension-in-pregnancy in Chinese: a meta-analysis. J Hum Hypertens. 2012;26:259–67.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ward M, Hughes CF, Strain JJ, Reilly R, Cunningham C, Molloy AM, Horigan G, Casey M, McCarroll K, O’Kane M, et al. Impact of the common MTHFR 677C–>T polymorphism on blood pressure in adulthood and role of riboflavin in modifying the genetic risk of hypertension: evidence from the JINGO project. BMC Med. 2020;18:318.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Horigan G, McNulty H, Ward M, Strain JJ, Purvis J, Scott JM. Riboflavin lowers blood pressure in cardiovascular disease patients homozygous for the 677C–>T polymorphism in MTHFR. J Hypertens. 2010;28:478–86.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wilson CP, Ward M, McNulty H, Strain JJ, Trouton TG, Horigan G, Purvis J, Scott JM. Riboflavin offers a targeted strategy for managing hypertension in patients with the MTHFR 677TT genotype: a 4-y follow-up. Am J Clin Nutr. 2012;95:766–72.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • McNulty H, Strain JJ, Hughes CF, Ward M. Riboflavin, MTHFR genotype and blood pressure: a personalized approach to prevention and treatment of hypertension. Mol Aspects Med. 2017;53:2–9.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Luo D, Cheng Y, Zhang H, Ba M, Chen P, Li H, Chen K, Sha W, Zhang C, Chen H. Association between high blood pressure and long term cardiovascular events in young adults: systematic review and meta-analysis. BMJ. 2020;370:m3222.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hypertension statistics [https://www.who.int/health-topics/hypertension#tab=tab_1]

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

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tummolo A, Leone P, Tolomeo M, Solito R, Mattiuzzo M, Lepri FR, Lore T, Cardinali R, De Giovanni D, Simonetti S, Barile M. Combined isobutyryl-CoA and multiple acyl-CoA dehydrogenase deficiency in a boy with altered riboflavin homeostasis. JIMD Rep. 2022;63:276–91.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Veitch K, Draye JP, Vamecq J, Causey AG, Bartlett K, Sherratt HS, Van Hoof F. Altered acyl-CoA metabolism in riboflavin deficiency. Biochim Biophys Acta. 1989;1006:335–43.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Nagao M, Tanaka K. FAD-dependent regulation of transcription, translation, post-translational processing, and post-processing stability of various mitochondrial acyl-CoA dehydrogenases and of electron transfer flavoprotein and the site of holoenzyme formation. J Biol Chem. 1992;267:17925–32.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zhu M, Zhu X, Qi X, Weijiang D, Yu Y, Wan H, Hong D. Riboflavin-responsive multiple Acyl-CoA dehydrogenation deficiency in 13 cases, and a literature review in mainland Chinese patients. J Hum Genet. 2014;59:256–61.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Liu XY, Chen XJ, Zhao M, Wang ZQ, Chen HZ, Li HF, Wang CJ, Wu SF, Peng C, Yin Y, et al. CHIP control degradation of mutant ETF:QO through ubiquitylation in late-onset multiple acyl-CoA dehydrogenase deficiency. J Inherit Metab Dis. 2021;44:450–68.

    Article 
    PubMed 

    Google Scholar
     

  • Gempel K, Topaloglu H, Talim B, Schneiderat P, Schoser BG, Hans VH, Palmafy B, Kale G, Tokatli A, Quinzii C, et al. The myopathic form of coenzyme Q10 deficiency is caused by mutations in the electron-transferring-flavoprotein dehydrogenase (ETFDH) gene. Brain. 2007;130:2037–44.

    Article 
    PubMed 

    Google Scholar
     

  • Brijlal S, Lakshmi AV. Tissue distribution and turnover of [3H]riboflavin during respiratory infection in mice. Metabolism. 1999;48:1608–11.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Mareska MC, Adams KK, Muenzer J, Frerman F, Braun TG, Howard JF Jr. Adult-onset presentation of glutaric acidemia type II with myopathy. J Clin Neuromuscul Dis. 2003;4:124–8.

    Article 
    PubMed 

    Google Scholar
     

  • Bates CJ, Prentice AM, Paul AA, Sutcliffe BA, Watkinson M, Whitehead RG. Riboflavin status in Gambian pregnant and lactating women and its implications for recommended dietary allowances. Am J Clin Nutr. 1981;34:928–35.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Heller S, Salkeld RM, Korner WF. Roboflavin status in pregnancy. Am J Clin Nutr. 1974;27:1225–30.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lin PY, Liang WC, Liao WA, Sun YT. Exacerbation of myopathy triggered by antiobesity drugs in a patient with multiple acyl-CoA dehydrogenase deficiency. BMC Neurol. 2021;21:93.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Papadimitriou A, Servidei S. Late onset lipid storage myopathy due to multiple acyl CoA dehydrogenase deficiency triggered by valproate. Neuromuscul Disord. 1991;1:247–52.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Hargreaves IP, Al Shahrani M, Wainwright L, Heales SJ. Drug-induced mitochondrial toxicity. Drug Saf. 2016;39:661–74.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Moren C, Juarez-Flores DL, Cardellach F, Garrabou G. The role of therapeutic drugs on acquired mitochondrial toxicity. Curr Drug Metab. 2016;17:648–62.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Goh LL, Lee Y, Tan ES, Lim JSC, Lim CW, Dalan R. Patient with multiple acyl-CoA dehydrogenase deficiency disease and ETFDH mutations benefits from riboflavin therapy: a case report. BMC Med Genomics. 2018;11:37.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hellebrekers D, Sallevelt S, Theunissen TEJ, Hendrickx ATM, Gottschalk RW, Hoeijmakers JGJ, Habets DD, Bierau J, Schoonderwoerd KG, Smeets HJM. Novel SLC25A32 mutation in a patient with a severe neuromuscular phenotype. Eur J Hum Genet. 2017;25:886–8.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Grier J, Hirano M, Karaa A, Shepard E, Thompson JLP. Diagnostic odyssey of patients with mitochondrial disease: Results of a survey. Neurol Genet. 2018;4:e230.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Deeny J. Riboflavin deficiency: with a case report. Br Med J. 1942;2:607.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Theunissen TEJ, Nguyen M, Kamps R, Hendrickx AT, Sallevelt S, Gottschalk RWH, Calis CM, Stassen APM, de Koning B, Mulder-Den Hartog ENM, et al. Whole exome sequencing is the preferred strategy to identify the genetic defect in patients with a probable or possible mitochondrial cause. Front Genet. 2018;9:400.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jaeger B, Bosch AM. Clinical presentation and outcome of riboflavin transporter deficiency: mini review after five years of experience. J Inherit Metab Dis. 2016;39:559–64.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Console L, Tolomeo M, Cosco J, Massey K, Barile M, Indiveri C. Impact of natural mutations on the riboflavin transporter 2 and their relevance to human riboflavin transporter deficiency 2. IUBMB Life. 2022;74:618–28.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Allison T, Roncero I, Forsyth R, Coffman K, Le Pichon JB. Brown–Vialetto–Van Laere syndrome as a mimic of neuroimmune disorders: 3 cases from the clinic and review of the literature. J Child Neurol. 2017;32:528–32.

    Article 
    PubMed 

    Google Scholar
     

  • Carey G, Kuchcinski G, Gauvrit F, Defebvre L, Nguyen S, Dhaenens CM, Dessein AF, Vianey-Saban C, Acquaviva C, Tard C. Three cases of adult-onset Brown–Vialetto–Van Laere syndrome: novel variants in SLC52A3 gene and MRI abnormalities. Neuromuscul Disord. 2021;31:752–5.

    Article 
    PubMed 

    Google Scholar
     

  • Chen HZ, Jin M, Cai NQ, Lin XD, Liu XY, Xu LQ, Lin MT, Lin F, Wang N, Wang ZQ, Xu GR. Rhabdomyolysis and respiratory insufficiency due to the common ETFDH mutation of c.250G>A in two patients with late-onset multiple acyl-CoA dehydrogenase deficiency. Chin Med J. 2019;132:1615–8.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

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

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • McNulty H, le Dowey RC, Strain JJ, Dunne A, Ward M, Molloy AM, McAnena LB, Hughes JP, Hannon-Fletcher M, Scott JM. Riboflavin lowers homocysteine in individuals homozygous for the MTHFR 677C->T polymorphism. Circulation. 2006;113:74–80.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H, Valentin F, Wallace IM, Wilm A, Lopez R, et al. Clustal W and Clustal X version 2.0. Bioinformatics. 2007;23:2947–8.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Humphrey W, Dalke A, Schulten K. VMD: visual molecular dynamics. J Mol Graph. 1996;14(33–38):27–38.


    Google Scholar
     



  • Source link