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Häberle J, Rubio V. Disorders of the urea cycle and related enzymes. In: Saudubray J-M, Baumgartner MR, Walter JH, editors. Inborn metabolic diseases: diagnosis and treatment. 6th ed. Berlin, Heidelberg: Springer; 2016. XXXI, pp. 295–308, 658 p. ISBN 978-3-662-49769-2.HäberleJRubioVDisorders of the urea cycle and related enzymesSaudubrayJ-MBaumgartnerMRWalterJHBerlin, HeidelbergSpringer201629530865810.1007/978-3-662-49771-5_19Search in Google Scholar
Häussinger D. Nitrogen metabolism in liver: structural and functional organization and physiological relevance. Biochem J. 1990;267(2):281–90. doi: 10.1042/bj2670281HäussingerDNitrogen metabolism in liver: structural and functional organization and physiological relevance199026722819010.1042/bj267028111312842185740Open DOISearch in Google Scholar
Ah Mew N, Simpson KL, Gropman AL, Lanpher BC, Chapman KA, Summar ML. Urea cycle disorders overview. 2003 Apr 29 [updated 2017 Jun 22]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, Genetic counseling, editors. GeneReviews® [Internet]. Seattle, WA: University of Washington; 1993–2020. ISSN 2372-0697.AhMew NSimpsonKLGropmanALLanpherBCChapmanKASummarML. Urea cycle disorders overview.2003Apr 29 [updated 2017 Jun 22]AdamMPArdingerHHPagonRAWallaceSEBeanLJHStephensKAmemiyaASeattle, WAUniversity of Washington;1993–2020ISSN 2372-0697Search in Google Scholar
Häberle J, Burlina A, Chakrapani A, Dixon M, Karall D, Lindner M, et al. Suggested guidelines for the diagnosis and management of urea cycle disorders: first revision. J Inherit Metab Dis. 2019;42(6):1192–230. doi: 10.1002/jimd.12100HäberleJBurlinaAChakrapaniADixonMKarallDLindnerMet alSuggested guidelines for the diagnosis and management of urea cycle disorders: first revision2019426119223010.1002/jimd.1210030982989Open DOISearch in Google Scholar
Tuchman M. The clinical, biochemical, and molecular spectrum of ornithine transcarbamylase deficiency. J Lab Clin Med. 1992;120(6):836–50.TuchmanMThe clinical, biochemical, and molecular spectrum of ornithine transcarbamylase deficiency1992120683650Search in Google Scholar
Tuchman M, Morizono H, Rajagopal BS, Plante RJ, Allewell NM. The biochemical and molecular spectrum of ornithine transcarbamylase deficiency. J Inherit Metab Dis. 1998;21(Suppl 1):40–58. doi: 10.1023/a:1005353407220TuchmanMMorizonoHRajagopalBSPlanteRJAllewellNMThe biochemical and molecular spectrum of ornithine transcarbamylase deficiency199821Suppl 1405810.1023/a:1005353407220Open DOISearch in Google Scholar
Häberle J. Clinical and biochemical aspects of primary and secondary hyperammonemic disorders. Arch Biochem Biophys. 2013;536(2):101–8. doi: 10.1016/j.abb.2013.04.009HäberleJClinical and biochemical aspects of primary and secondary hyperammonemic disorders20135362101810.1016/j.abb.2013.04.00923628343Open DOISearch in Google Scholar
Summar ML, Koelker S, Freedenberg D, Le Mons C, Haberle J, Lee HS, et al.; European Registry and Network for Intoxication Type Metabolic Diseases (E-IMD). Electronic address: http://www.e-imd.org/en/index.phtml; Members of the Urea Cycle Disorders Consortium (UCDC). Electronic address: http://rarediseasesnetwork.epi.usf.edu/ucdc/. The incidence of urea cycle disorders. Mol Genet Metab. 2013;110(1–2):179–80. doi: 10.1016/j.ymgme.2013.07.008SummarMLKoelkerSFreedenbergDLe MonsCHaberleJLeeHSet alElectronic addresshttp://www.e-imd.org/en/index.phtmlMembers of the Urea Cycle Disorders Consortium (UCDC). Electronic addresshttp://rarediseasesnetwork.epi.usf.edu/ucdc/The incidence of urea cycle disorders. Mol Genet Metab20131101–21798010.1016/j.ymgme.2013.07.008436441323972786Open DOISearch in Google Scholar
Sancho-Vaello E, Marco-Marín C, Gougeard N, Fernández-Murga L, Rüfenacht V, Mustedanagic M, et al. Understanding N-acetyl-L-glutamate synthase deficiency: mutational spectrum, impact of clinical mutations on enzyme functionality, and structural considerations. Hum Mutat. 2016;37(7):679–94. doi: 10.1002/humu.22995Sancho-VaelloEMarco-MarínCGougeardNFernández-MurgaLRüfenachtVMustedanagicMet alUnderstanding N-acetyl-L-glutamate synthase deficiency: mutational spectrum, impact of clinical mutations on enzyme functionality, and structural considerations20163776799410.1002/humu.2299527037498Open DOISearch in Google Scholar
Dimmock D, Maranda B, Dionisi-Vici C, Wang J, Kleppe S, Fiermonte G, et al. Citrin deficiency, a perplexing global disorder. Mol Genet Metab. 2009;96(1):44–9. doi: 10.1016/j. ymgme.2008.10.007DimmockDMarandaBDionisi-ViciCWangJKleppeSFiermonteGet alCitrin deficiency, a perplexing global disorder200996144910.1016/j.ymgme.2008.10.00719036621Open DOISearch in Google Scholar
Saheki T, Inoue K, Tushima A, Mutoh K, Kobayashi K. Citrin deficiency and current treatment concepts. Mol Genet Metab. 2010;100(Suppl 1):S59–64. doi: 10.1016/j.ymgme.2010.02.014SahekiTInoueKTushimaAMutohKKobayashiKCitrin deficiency and current treatment concepts2010100Suppl 1S596410.1016/j.ymgme.2010.02.01420233664Open DOISearch in Google Scholar
Caldovic L, Abdikarim I, Narain S, Tuchman M, Morizono H. Genotype-phenotype correlations in ornithine transcarbamylase deficiency: a mutation update. J Genet Genomics. 2015;42(5): 181–94. doi: 10.1016/j.jgg.2015.04.003CaldovicLAbdikarimINarainSTuchmanMMorizonoHGenotype-phenotype correlations in ornithine transcarbamylase deficiency: a mutation update20154251819410.1016/j.jgg.2015.04.003456514026059767Open DOISearch in Google Scholar
Gropman AL, Summar M, Leonard JV. Neurological implications of urea cycle disorders. J Inherit Metab Dis. 2007;30(6):865–79. doi: 10.1007/s10545-007-0709-5GropmanALSummarMLeonardJVNeurological implications of urea cycle disorders20073068657910.1007/s10545-007-0709-5375869318038189Open DOISearch in Google Scholar
Braissant O. Current concepts in the pathogenesis of urea cycle disorders. Mol Genet Metab. 2010;100(Suppl 1):S3–12. doi: 10.1016/j.ymgme.2010.02.010BraissantOCurrent concepts in the pathogenesis of urea cycle disorders2010100Suppl 1S31210.1016/j.ymgme.2010.02.01020227314Open DOISearch in Google Scholar
Braissant O, McLin VA, Cudalbu C. Ammonia toxicity to the brain. J Inherit Metab Dis. 2013;36(4):595–612. doi: 10.1007/s10545-012-9546-2BraissantOMcLinVACudalbuCAmmonia toxicity to the brain201336459561210.1007/s10545-012-9546-223109059Open DOISearch in Google Scholar
Leonard JV, Morris AA. Urea cycle disorders. Semin Neonatol. 2002;7(1):27–35. doi: 10.1053/siny.2001.0085LeonardJVMorrisAAUrea cycle disorders200271273510.1053/siny.2001.008512069536Open DOISearch in Google Scholar
Nassogne MC, Héron B, Touati G, Rabier D, Saudubray JM. Urea cycle defects: management and outcome. J Inherit Metab Dis. 2005;28(3):407–14. doi: 10.1007/s10545-005-0303-7NassogneMCHéronBTouatiGRabierDSaudubrayJMUrea cycle defects: management and outcome20052834071410.1007/s10545-005-0303-715868473Open DOISearch in Google Scholar
Serrano M, Martins C, Pérez-Dueñas B, Gómez-López L, Murgui E, Fons C, et al. Neuropsychiatric manifestations in late-onset urea cycle disorder patients. J Child Neurol. 2010;25(3):352–8. doi: 10.1177/0883073809340696SerranoMMartinsCPérez-DueñasBGómez-LópezLMurguiEFonsCet alNeuropsychiatric manifestations in late-onset urea cycle disorder patients2010253352810.1177/088307380934069619684305Open DOISearch in Google Scholar
Fantur M, Karall D, Scholl-Buergi S, Häberle J, Rauchenzauner M, Fruehwirth M. Recurrent somnolence in a 17-month-old infant: late-onset ornithine transcarbamylase (OTC) deficiency due to the novel hemizygous mutation c.535C > T (p.Leu179Phe). Eur J Paediatr Neurol. 2013;17(1):112–5. doi: 10.1016/j. ejpn.2012.05.007FanturMKarallDScholl-BuergiSHäberleJRauchenzaunerMFruehwirthMRecurrent somnolence in a 17-month-old infant: late-onset ornithine transcarbamylase (OTC) deficiency due to the novel hemizygous mutation c.535C > T (p.Leu179Phe)2013171112510.1016/j.ejpn.2012.05.00722727265Open DOISearch in Google Scholar
Ihara K, Yoshino M, Hoshina T, Harada N, Kojima-Ishii K, Makimura M, et al. Coagulopathy in patients with late-onset ornithine transcarbamylase deficiency in remission state: a previously unrecognized complication. Pediatrics. 2013;131(1):e327–30. doi: 10.1542/peds.2012-0030IharaKYoshinoMHoshinaTHaradaNKojima-IshiiKMakimuraMet alCoagulopathy in patients with late-onset ornithine transcarbamylase deficiency in remission state: a previously unrecognized complication20131311e3273010.1542/peds.2012-003023209112Open DOISearch in Google Scholar
Gropman AL, Batshaw ML. Cognitive outcome in urea cycle disorders. Mol Genet Metab. 2004;81(Suppl 1):S58–62. doi: 10.1016/j.ymgme.2003.11.016GropmanALBatshawMLCognitive outcome in urea cycle disorders200481Suppl 1S586210.1016/j.ymgme.2003.11.01615050975Open DOISearch in Google Scholar
Gropman AL, Prust M, Breeden A, Fricke S, VanMeter J. Urea cycle defects and hyperammonemia: effects on functional imaging. Metab Brain Dis. 2013;28(2):269–75. doi: 10.1007/s11011-012-9348-0GropmanALPrustMBreedenAFrickeSVanMeterJUrea cycle defects and hyperammonemia: effects on functional imaging20132822697510.1007/s11011-012-9348-0359435623149878Open DOISearch in Google Scholar
Hediger N, Landolt MA, Diez-Fernandez C, Huemer M, Häberle J. The impact of ammonia levels and dialysis on outcome in 202 patients with neonatal onset urea cycle disorders. J Inherit Metab Dis. 2018;41(4):689–98. doi: 10.1007/s10545-018-0157-4HedigerNLandoltMADiez-FernandezCHuemerMHäberle JThe impact of ammonia levels and dialysis on outcome in 202 patients with neonatal onset urea cycle disorders20184146899810.1007/s10545-018-0157-429520739Open DOISearch in Google Scholar
Vergano SA, Crossette JM, Cusick FC, Desai BR, Deardorff MA, Sondheimer N. Improving surveillance for hyperammonemia in the newborn. Mol Genet Metab. 2013;110(1–2):102–5. doi: 10.1016/j.ymgme.2013.05.005VerganoSACrossetteJMCusickFCDesaiBRDeardorffMASondheimerNImproving surveillance for hyperammonemia in the newborn20131101–2102510.1016/j.ymgme.2013.05.005375501623746553Open DOISearch in Google Scholar
Häberle J, Rubio V. Hyperammonemias and related disorders. pp. 47–62. doi: 10.1007/978-3-642-40337-8_4. In: Blau N, Duran M, Gibsin KM, Dionisi-Vici C, editors. Physician’s guide to the diagnosis, treatment, and follow-up of inherited metabolic diseases. Berlin, Heidelberg: Springer; 2014; XLV, 867 p. ISBN 978-3-642-40336-1. eBook ISBN 978-3-642-40337-8. doi: 10.1007/978-3-642-40337-8.HäberleJRubioV476210.1007/978-3-642-40337-8_4In: Blau N, Duran M, Gibsin KM, Dionisi-Vici C, editors. Physician’s guide to the diagnosis, treatment, and follow-up of inherited metabolic diseases. Berlin, Heidelberg: Springer; 2014; XLV, 867 p. ISBN 978-3-642-40336-1. eBook ISBN 978-3-642-40337-810.1007/978-3-642-40337-8Open DOISearch in Google Scholar
Häberle J, Koch HG. Genetic approach to prenatal diagnosis in urea cycle defects. Prenat Diagn. 2004;24(5):378–83. doi: 10.1002/pd.884HäberleJKochHGGenetic approach to prenatal diagnosis in urea cycle defects20042453788310.1002/pd.88415164414Open DOISearch in Google Scholar
Gautschi M, Eggimann S, Nuofer J-M. Current role of enzyme analysis for urea cycle disorders. J Pediatr Biochem. 2014;4(1):23–32. doi: 10.3233/JPB-140103GautschiMEggimannSNuoferJ-MCurrent role of enzyme analysis for urea cycle disorders201441233210.3233/JPB-140103Open DOISearch in Google Scholar
Yudkof M, Ah Mew N, Daikhin Y, Horyn O, Nissim I, Nissim I, et al. Measuring in vivo ureagenesis with stable isotopes. Mol Genet Metab. 2010;100(Suppl 1):S37–41. doi: 10.1016/j. ymgme.2010.02.017YudkofMAhMew NDaikhinYHorynONissimINissimIet alMeasuring in vivo ureagenesis with stable isotopes2010100Suppl 1S374110.1016/j.ymgme.2010.02.017285879320338795Open DOISearch in Google Scholar
Yudkof M, Daikhin Y, Ye X, Wilson JM, Batshaw ML. In vivo measurement of ureagenesis with stable isotopes. J Inherit Metab Dis. 1998;21(Suppl 1):21–9. doi: 10.1023/a:1005345205403YudkofMDaikhinYYeXWilsonJMBatshawMLIn vivo measurement of ureagenesis with stable isotopes199821Suppl 121910.1023/a:1005345205403Open DOISearch in Google Scholar
Mew NA, Yudkoff M, Tuchman M. Stable isotopes in the diagnosis and treatment of inherited hyperammonemia. J Pediatr Biochem. 2014;4(1):57–63. doi: 10.3233/JPB-140106MewNAYudkoffMTuchmanMStable isotopes in the diagnosis and treatment of inherited hyperammonemia201441576310.3233/JPB-140106395200224634704Open DOISearch in Google Scholar
Allegri G, Deplazes S, Grisch-Chan HM, Mathis D, Fingerhut R, Häberle J, et al. A simple dried blood spot-method for in vivo measurement of ureagenesis by gas chromatography-mass spectrometry using stable isotopes. Clin Chim Acta. 2017;464:236–43. doi: 10.1016/j.cca.2016.11.038AllegriGDeplazesSGrisch-ChanHMMathisDFingerhutRHäberleJet alA simple dried blood spot-method for in vivo measurement of ureagenesis by gas chromatography-mass spectrometry using stable isotopes20174642364310.1016/j.cca.2016.11.03827923571Open DOISearch in Google Scholar
Ah Mew N, McCarter R, Daikhin Y, Lichter-Konecki U, Nissim I, Yudkof M, et al. Augmenting ureagenesis in patients with partial carbamyl phosphate synthetase 1 deficiency with N-carbamyl-L-glutamate. J Pediatr. 2014;165(2):401–3.e3. doi: 10.1016/j. jpeds.2014.04.012AhMew NMcCarterRDaikhinYLichter-KoneckiUNissimIYudkofMet alAugmenting ureagenesis in patients with partial carbamyl phosphate synthetase 1 deficiency with N-carbamyl-L-glutamate20141652401310.1016/j.jpeds.2014.04.012411199324880889Open DOISearch in Google Scholar
Häberle J. Clinical practice: the management of hyperammonemia. Eur J Pediatr. 2011;170(1):21–34. doi: 10.1007/s00431-010-1369-2HäberleJClinical practice: the management of hyperammonemia20111701213410.1007/s00431-010-1369-221165747Open DOISearch in Google Scholar
Picca S, Bartuli A, Dionisi-Vici C. Medical management and dialysis therapy for the infant with an inborn error of metabolism. Semin Nephrol. 2008;28(5):477–80. doi: 10.1016/j. semnephrol.2008.05.007PiccaSBartuliADionisi-ViciCMedical management and dialysis therapy for the infant with an inborn error of metabolism20082854778010.1016/j.semnephrol.2008.05.00718790367Open DOISearch in Google Scholar
Picca S, Dionisi-Vici C, Abeni D, Pastore A, Rizzo C, Orzalesi M, et al. Extracorporeal dialysis in neonatal hyperammonemia: modalities and prognostic indicators. Pediatr Nephrol. 2001;16(11):862–7. doi: 10.1007/s004670100702PiccaSDionisi-ViciCAbeniDPastoreARizzoCOrzalesiMet alExtracorporeal dialysis in neonatal hyperammonemia: modalities and prognostic indicators20011611862710.1007/s00467010070211685590Open DOISearch in Google Scholar
Dixon M, MacDonald A, White F, Stafford J. Disorders of amino acid metabolism, organic acidaemias and urea cycle disorders. p. 381–525. doi: 10.1002/9781118915349.ch17. In: Shaw V, editor. Clinical paediatric dietetics. 4th ed. Chichester, West Sussex: John Wiley & Sons Ltd.; 2015; 864 p. ISBN 978-0470659984. Online ISBN: 978-1118915349. doi: 10.1002/9781118915349.DixonMMacDonaldAWhiteFStaffordJ381–52510.1002/9781118915349.ch17In: Shaw V, editor. Clinical paediatric dietetics. 4th ed. Chichester, West Sussex: John Wiley & Sons Ltd.; 2015; 864 p. ISBN 978-0470659984. Online ISBN: 978-111891534910.1002/9781118915349Open DOISearch in Google Scholar
Burlina AB. Hepatocyte transplantation for inborn errors of metabolism. J Inherit Metab Dis. 2004;27(3):373–83. doi: 10.1023/B:BOLI.0000031095.57411.8dBurlinaABHepatocyte transplantation for inborn errors of metabolism20042733738310.1023/B:BOLI.0000031095.57411.8dOpen DOISearch in Google Scholar
Gallicano GI, Mishra L. Hepatocytes from induced pluripotent stem cells: a giant leap forward for hepatology. Hepatology. 2010;51(1):20–2. doi: 10.1002/hep.23474GallicanoGIMishraLHepatocytes from induced pluripotent stem cells: a giant leap forward for hepatology201051120210.1002/hep.23474382155520034034Open DOISearch in Google Scholar
Puppi J, Tan N, Mitry RR, Hughes RD, Lehec S, Mieli-Vergani G, et al. Hepatocyte transplantation followed by auxiliary liver transplantation – a novel treatment for ornithine transcarbamylase deficiency. Am J Transplant. 2008;8(2):452–7. doi: 10.1111/j.1600-6143.2007.02058.xPuppiJTanNMitryRRHughesRDLehecSMieli-VerganiGet alHepatocyte transplantation followed by auxiliary liver transplantation – a novel treatment for ornithine transcarbamylase deficiency200882452710.1111/j.1600-6143.2007.02058.x18211511Open DOISearch in Google Scholar
Spada M, Porta F, Righi D, Gazzera C, Tandoi F, Ferrero I, et al. Intrahepatic administration of human liver stem cells in infants with inherited neonatal-onset hyperammonemia: a phase i study. Stem Cell Rev Rep. 2020;16(1):186–97. doi: 10.1007/s12015-019-09925-zSpadaMPortaFRighiDGazzeraCTandoiFFerreroIet alIntrahepatic administration of human liver stem cells in infants with inherited neonatal-onset hyperammonemia: a phase i study20201611869710.1007/s12015-019-09925-z698713431792768Open DOISearch in Google Scholar
Wilson JM. Lessons learned from the gene therapy trial for ornithine transcarbamylase deficiency. Mol Genet Metab. 2009;96(4):151–7. doi: 10.1016/j.ymgme.2008.12.016WilsonJMLessons learned from the gene therapy trial for ornithine transcarbamylase deficiency2009964151710.1016/j.ymgme.2008.12.01619211285Open DOISearch in Google Scholar
Wang L, Bell P, Morizono H, He Z, Pumbo E, Yu H, et al. AAV gene therapy corrects OTC deficiency and prevents liver fibrosis in aged OTC-knock out heterozygous mice. Mol Genet Metab. 2017;120(4):299–305. doi: 10.1016/j.ymgme.2017.02.011WangLBellPMorizonoHHeZPumboEYuHet alAAV gene therapy corrects OTC deficiency and prevents liver fibrosis in aged OTC-knock out heterozygous mice2017120429930510.1016/j.ymgme.2017.02.011542326728283349Open DOISearch in Google Scholar
Burrage LC, Sun Q, Elsea SH, Jiang MM, Nagamani SC, Frankel AE, et al. Human recombinant arginase enzyme reduces plasma arginine in mouse models of arginase deficiency. Hum Mol Genet. 2015;24(22):6417–27. doi: 10.1093/hmg/ddv352BurrageLCSunQElseaSHJiangMMNagamaniSCFrankelAEet alHuman recombinant arginase enzyme reduces plasma arginine in mouse models of arginase deficiency2015242264172710.1093/hmg/ddv352500760826358771Open DOISearch in Google Scholar