Skip to main content

Advertisement

SpringerLink
Log in

Hyperargininemia due to arginase I deficiency: the original patients and their natural history, and a review of the literature

  • Review Article
  • Published:
Amino Acids Aims and scope Submit manuscript

Abstract

Hyperargininemia is caused by deficiency of arginase 1, which catalyzes the hydrolysis of l-arginine to urea as the final enzyme in the urea cycle. In contrast to other urea cycle defects, arginase 1 deficiency usually does not cause catastrophic neonatal hyperammonemia but rather presents with progressive neurological symptoms including seizures and spastic paraplegia in the first years of life and hepatic pathology, such as neonatal cholestasis, acute liver failure, or liver fibrosis. Some patients have developed hepatocellular carcinoma. A usually mild or moderate hyperammonemia may occur at any age. The pathogenesis of arginase I deficiency is yet not fully understood. However, the accumulation of l-arginine and the resulting abnormalities in the metabolism of guanidine compounds and nitric oxide have been proposed to play a major pathophysiological role. This article provides an update on the first patients ever described, gives an overview of the distinct clinical characteristics, biochemical as well as genetical background and discusses treatment options.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

AGAT:

l-Arginine-glycine amidinotransferase

ASL:

Argininosuccinate lyase

ASS:

Argininosuccinate synthase

CSF:

Cerebrospinal fluid

CPSI:

Carbamoyl phosphate synthase I

GAA:

Guanidinoacetate

GAMT:

Guanidinoacetatemethyltransferase

GC:

Guanidino compounds

NAGS:

N-Acetyl-glutamate synthase

NO:

Nitric oxide

NOS:

Nitric oxide synthase

MRI:

Magnetic resonance imaging

MRS:

Magnetic resonance spectroscopy

ORNT1:

Mitochondrial ornithine transporter

OAT:

Ornithine aminotransferase

OTC:

Ornithine transcarbamylase

UCD:

Urea cycle disorder

References

  • Amayreh W, Meyer U, Das AM (2014) Treatment of arginase deficiency revisited: guanidinoacetate as a therapeutic target and biomarker for therapeutic monitoring. Dev Med Child Neurol 56(10):1021–1024. doi:10.1111/dmcn.12488

    Article  PubMed  Google Scholar 

  • Ash DE, Scolnick LR, Kanyo ZF, Vockley JG, Cederbaum SD, Christianson DW (1998) Molecular basis of hyperargininemia: structure-function consequences of mutations in human liver arginase. Mol Genet Metab 64(4):243–249. doi:10.1006/mgme.1998.2677

    Article  CAS  PubMed  Google Scholar 

  • Bachmann C, Colombo JP (1980) Diagnostic value of orotic acid excretion in heritable disorders of the urea cycle and in hyperammonemia due to organic acidurias. Eur J Pediatr 134(2):109–113

    Article  CAS  PubMed  Google Scholar 

  • Bachmann C, Colombo JP (1982) Orotic acid in urine and hyperammonemia. Adv Exp Med Biol 153:313–319

    Article  CAS  PubMed  Google Scholar 

  • Bachmann C, Krahenbuhl S, Colombo JP (1982) Purification and properties of acetyl-CoA: l-glutamate N-acetyltransferase from human liver. Biochem J 205(1):123–127

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Baranello G, Alfei E, Martinelli D, Rizzetto M, Cazzaniga F, Dionisi-Vici C, Gellera C, Castellotti B (2014) Hyperargininemia: 7-month follow-up under sodium benzoate therapy in an Italian child presenting progressive spastic paraparesis, cognitive decline, and novel mutation in ARG1 gene. Pediatr Neurol 51(3):430–433. doi:10.1016/j.pediatrneurol.2014.05.029

    Article  PubMed  Google Scholar 

  • Batshaw ML, MacArthur RB, Tuchman M (2001) Alternative pathway therapy for urea cycle disorders: twenty years later. J Pediatrics 138 (1 Suppl):S46–S54; discussion S54–S45

  • Batshaw ML, Tuchman M, Summar M, Seminara J, Members of the Urea Cycle Disorders C (2014) A longitudinal study of urea cycle disorders. Mol Genet Metab 113(1–2):127–130. doi:10.1016/j.ymgme.2014.08.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bernard A, Meier C, Lopez N, May J, Chang P, Boulanger B, Kearney P (2007) Packed red blood cell-associated arginine depletion is mediated by arginase. J Trauma 63 (5):1108–1112; discussion 1112. doi:10.1097/TA.0b013e31814b2b17

  • Blaser S, Feigenbaum A (2004) A neuroimaging approach to inborn errors of metabolism. Neuroimag Clin North Am 14 (2):307–329, ix. doi:10.1016/j.nic.2004.03.013

  • Boles RG, Stone ML (2006) A patient with arginase deficiency and episodic hyperammonemia successfully treated with menses cessation. Mol Genet Metab 89(4):390–391. doi:10.1016/j.ymgme.2006.07.012

    Article  CAS  PubMed  Google Scholar 

  • Bonham JR, Guthrie P, Downing M, Allen JC, Tanner MS, Sharrard M, Rittey C, Land JM, Fensom A, O’Neill D, Duley JA, Fairbanks LD (1999) The allopurinol load test lacks specificity for primary urea cycle defects but may indicate unrecognized mitochondrial disease. J Inherit Metab Dis 22(2):174–184

    Article  CAS  PubMed  Google Scholar 

  • Braga AC, Vilarinho L, Ferreira E, Rocha H (1997) Hyperargininemia presenting as persistent neonatal jaundice and hepatic cirrhosis. J Pediatr Gastroenterol Nutr 24(2):218–221

    Article  CAS  PubMed  Google Scholar 

  • Brockstedt M, Smit LM, de Grauw AJ, van der Klei-van Moorsel JM, Jakobs C (1990) A new case of hyperargininaemia: neurological and biochemical findings prior to and during dietary treatment. Eur J Pediatr 149(5):341–343

    Article  CAS  PubMed  Google Scholar 

  • Brosnan ME, Brosnan JT (2007) Orotic acid excretion and arginine metabolism. J Nutr 137(6 Suppl 2):1656S–1661S

    CAS  PubMed  Google Scholar 

  • Brusilow SWHA (2001) Urea cycle enzymes. In: Scriver CRBA, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease. McGraw-Hill, New York, pp 1909–1963

    Google Scholar 

  • Buchmann I, Milakofsky L, Harris N, Hofford JM, Vogel WH (1996) Effect of arginine administration on plasma and brain levels of arginine and various related amino compounds in the rat. Pharmacology 53(3):133–142

    Article  CAS  PubMed  Google Scholar 

  • Caldovic L, Ah Mew N, Shi D, Morizono H, Yudkoff M, Tuchman M (2010) N-acetylglutamate synthase: structure, function and defects. Mol Genet Metab 100(Suppl 1):S13–S19. doi:10.1016/j.ymgme.2010.02.018

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Camacho JA, Obie C, Biery B, Goodman BK, Hu CA, Almashanu S, Steel G, Casey R, Lambert M, Mitchell GA, Valle D (1999) Hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrome is caused by mutations in a gene encoding a mitochondrial ornithine transporter. Nat Genet 22(2):151–158. doi:10.1038/9658

    Article  CAS  PubMed  Google Scholar 

  • Cardoso ML, Martins E, Vasconcelos R, Vilarinho L, Rocha J (1999) Identification of a novel R21X mutation in the liver-type arginase gene (ARG1) in four Portuguese patients with argininemia. Hum Mutat 14(4):355–356. doi:10.1002/(SICI)1098-1004(199910)14:4<355:AID-HUMU20>3.0.CO;2-I

    Article  CAS  PubMed  Google Scholar 

  • Carvalho DR, Brand GD, Brum JM, Takata RI, Speck-Martins CE, Pratesi R (2012a) Analysis of novel ARG1 mutations causing hyperargininemia and correlation with arginase I activity in erythrocytes. Gene 509(1):124–130. doi:10.1016/j.gene.2012.08.003

    Article  CAS  PubMed  Google Scholar 

  • Carvalho DR, Brum JM, Speck-Martins CE, Ventura FD, Navarro MM, Coelho KE, Portugal D, Pratesi R (2012b) Clinical features and neurologic progression of hyperargininemia. Pediatr Neurol 46(6):369–374. doi:10.1016/j.pediatrneurol.2012.03.016

    Article  PubMed  Google Scholar 

  • Cederbaum SD, Shaw KN, Valente M (1977) Hyperargininemia. J Pediatr 90(4):569–573

    Article  CAS  PubMed  Google Scholar 

  • Cederbaum SD, Shaw KN, Spector EB, Verity MA, Snodgrass PJ, Sugarman GI (1979) Hyperargininemia with arginase deficiency. Pediatr Res 13(7):827–833. doi:10.1203/00006450-197907000-00007

    Article  CAS  PubMed  Google Scholar 

  • Cederbaum SD, Moedjono SJ, Shaw KN, Carter M, Naylor E, Walzer M (1982) Treatment of hyperargininaemia due to arginase deficiency with a chemically defined diet. J Inherit Metab Dis 5(2):95–99

    Article  CAS  PubMed  Google Scholar 

  • Cederbaum SD, Yu H, Grody WW, Kern RM, Yoo P, Iyer RK (2004) Arginases I and II: do their functions overlap? Mol Genet Metab 81(Suppl 1):S38–S44. doi:10.1016/j.ymgme.2003.10.012

    Article  CAS  PubMed  Google Scholar 

  • Chace DH, Kalas TA, Naylor EW (2002) The application of tandem mass spectrometry to neonatal screening for inherited disorders of intermediary metabolism. Annu Rev Genom Hum Genet 3:17–45. doi:10.1146/annurev.genom.3.022502.103213

    Article  CAS  Google Scholar 

  • Choi CG, Yoo HW (2001) Localized proton MR spectroscopy in infants with urea cycle defect. AJNR Am J Neuroradiol 22(5):834–837

    CAS  PubMed  Google Scholar 

  • Christmann D, Hirsch E, Mutschler V, Collard M, Marescaux C, Colombo JP (1990) Late diagnosis of congenital argininemia during administration of sodium valproate. Revue Neurologique 146(12):764–766

    CAS  PubMed  Google Scholar 

  • Chrzanowska A, Gajewska B, Baranczyk-Kuzma A (2009) Arginase isoenzymes in human cirrhotic liver. Acta Biochim Pol 56(3):465–469

    CAS  PubMed  Google Scholar 

  • Cohen YH, Bargal R, Zeigler M, Markus-Eidlitz T, Zuri V, Zeharia A (2012) Hyperargininemia: a family with a novel mutation in an unexpected site. JIMD Rep 5:83–88. doi:10.1007/8904_2011_101

    Article  PubMed Central  PubMed  Google Scholar 

  • Cowley DM, Bowling FG, McGill JJ, van Dongen J, Morris D (1998) Adult-onset arginase deficiency. J Inherit Metab Dis 21(6):677–678

    Article  CAS  PubMed  Google Scholar 

  • Crombez EA, Cederbaum SD (2005) Hyperargininemia due to liver arginase deficiency. Mol Genet Metab 84(3):243–251. doi:10.1016/j.ymgme.2004.11.004

    Article  CAS  PubMed  Google Scholar 

  • da Silva CG, Parolo E, Streck EL, Wajner M, Wannmacher CM, Wyse AT (1999) In vitro inhibition of Na + , K(+)-ATPase activity from rat cerebral cortex by guanidino compounds accumulating in hyperargininemia. Brain Res 838(1–2):78–84

    Article  PubMed  Google Scholar 

  • De Deyn PP, Marescau B, Macdonald RL (1991) Guanidino compounds that are increased in hyperargininemia inhibit GABA and glycine responses on mouse neurons in cell culture. Epilepsy Res 8(2):134–141

    Article  PubMed  Google Scholar 

  • De Deyn PP, Qureshi IA et al (1997) Hyperargininemia: a treatable inborn error of metabolism? In: De Deyn PP, Quresho IA, Mori A (eds) Guanidino compounds in biology and medicine, vol 2. John Libbey & Company Ltd., London, pp 53–69

    Google Scholar 

  • Deignan JL, De Deyn PP, Cederbaum SD, Fuchshuber A, Roth B, Gsell W, Marescau B (2010) Guanidino compound levels in blood, cerebrospinal fluid, and post-mortem brain material of patients with argininemia. Mol Genet Metab 100(Suppl 1):S31–S36. doi:10.1016/j.ymgme.2010.01.012

    Article  CAS  PubMed  Google Scholar 

  • Delwing D, Tagliari B, Streck EL, Wannamacher CM, Wajner M, Wyse AT (2003) Reduction of energy metabolism in rat hippocampus by arginine administration. Brain Res 983(1–2):58–63

    Article  CAS  PubMed  Google Scholar 

  • Delwing D, Delwing D, Bavaresco CS, Wyse AT (2008) Protective effect of nitric oxide synthase inhibition or antioxidants on brain oxidative damage caused by intracerebroventricular arginine administration. Brain Res 1193:120–127. doi:10.1016/j.brainres.2007.11.052

    Article  CAS  PubMed  Google Scholar 

  • Delwing-de Lima D, Wollinger LF, Casagrande AC, Delwing F, da Cruz JG, Wyse AT, Delwing-Dal Magro D (2010) Guanidino compounds inhibit acetylcholinesterase and butyrylcholinesterase activities: effect neuroprotector of vitamins E plus C. Int J Dev Neurosci Offi J Int Soc Dev Neurosci 28(6):465–473. doi:10.1016/j.ijdevneu.2010.06.008

    Article  CAS  Google Scholar 

  • dos Reis EA, de Oliveira LS, Lamers ML, Netto CA, Wyse AT (2002) Arginine administration inhibits hippocampal Na(+), K(+)-ATPase activity and impairs retention of an inhibitory avoidance task in rats. Brain Res 951(2):151–157

    Article  PubMed  Google Scholar 

  • Edwards RL, Moseley K, Watanabe Y, Wong LJ, Ottina J, Yano S (2009) Long-term neurodevelopmental effects of early detection and treatment in a 6-year-old patient with argininaemia diagnosed by newborn screening. J Inherit Metab Dis 32(Suppl 1):S197–S200. doi:10.1007/s10545-009-1148-2

    Article  PubMed  Google Scholar 

  • Grioni D, Furlan F, Canonico F, Parini R (2014) Epilepsia partialis continua and generalized nonconvulsive status epilepticus during the course of argininemia: a report on two cases. Neuropediatrics 45(2):123–128. doi:10.1055/s-0033-1360479

    CAS  PubMed  Google Scholar 

  • Grody WW, Argyle C, Kern RM, Dizikes GJ, Spector EB, Strickland AD, Klein D, Cederbaum SD (1989) Differential expression of the two human arginase genes in hyperargininemia. Enzymatic, pathologic, and molecular analysis. J Clin Investig 83(2):602–609. doi:10.1172/JCI113923

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Grody WW, Kern RM, Klein D, Dodson AE, Wissman PB, Barsky SH, Cederbaum SD (1993) Arginase deficiency manifesting delayed clinical sequelae and induction of a kidney arginase isozyme. Hum Genet 91(1):1–5

    Article  CAS  PubMed  Google Scholar 

  • Grody WW, Chang RJ, Panagiotis NM, Matz D, Cederbaum SD (1994) Menstrual cycle and gonadal steroid effects on symptomatic hyperammonaemia of urea-cycle-based and idiopathic aetiologies. J Inherit Metab Dis 17(5):566–574

    Article  CAS  PubMed  Google Scholar 

  • Gropman AL, Summar M, Leonard JV (2007) Neurological implications of urea cycle disorders. J Inherit Metab Dis 30(6):865–879. doi:10.1007/s10545-007-0709-5

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Gungor S, Akinci A, Firat AK, Tabel Y, Alkan A (2008) Neuroimaging findings in hyperargininemia. J Neuroimag Offi J Am Soc Neuroimag 18(4):457–462. doi:10.1111/j.1552-6569.2007.00217.x

    Article  Google Scholar 

  • Haberle J, Boddaert N, Burlina A, Chakrapani A, Dixon M, Huemer M, Karall D, Martinelli D, Crespo PS, Santer R, Servais A, Valayannopoulos V, Lindner M, Rubio V, Dionisi-Vici C (2012) Suggested guidelines for the diagnosis and management of urea cycle disorders. Orphanet J Rare Diseases 7:32. doi:10.1186/1750-1172-7-32

    Article  Google Scholar 

  • Haraguchi Y, Takiguchi M, Amaya Y, Kawamoto S, Matsuda I, Mori M (1987) Molecular cloning and nucleotide sequence of cDNA for human liver arginase. Proc Natl Acad Sci USA 84(2):412–415

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hertecant JL, Al-Gazali LI, Karuvantevida NS, Ali BR (2009) A novel mutation in ARG1 gene is responsible for arginase deficiency in an Asian family. Saudi Med J 30(12):1601–1603

    PubMed  Google Scholar 

  • Hewson S, Clarke JT, Cederbaum S (2003) Prenatal diagnosis for arginase deficiency: a case study. J Inherit Metab Dis 26(6):607–610

    Article  CAS  PubMed  Google Scholar 

  • Hiramatsu M (2003) A role for guanidino compounds in the brain. Mol Cell Biochem 244(1–2):57–62

    Article  CAS  PubMed  Google Scholar 

  • Jain-Ghai S, Nagamani SC, Blaser S, Siriwardena K, Feigenbaum A (2011) Arginase I deficiency: severe infantile presentation with hyperammonemia: more common than reported? Mol Genet Metab 104(1–2):107–111. doi:10.1016/j.ymgme.2011.06.025

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Jorda A, Rubio V, Portoles M, Vilas J, Garcia-Pino J (1986) A new case of arginase deficiency in a Spanish male. J Inherit Metab Dis 9(4):393–397

    Article  CAS  PubMed  Google Scholar 

  • Jorda A, Portoles M, Rubio V, Capdevila A, Vilas J, Garcia-Pino J (1987) Liver fibrosis in arginase deficiency. Arch Pathol Lab Med 111(8):691–692

    CAS  PubMed  Google Scholar 

  • Kayali Z, Herring J, Baron P, Franco E, Ojogho O, Smith J, Watkins G, Smith D, Lamin V, Hoang T, Sharma R, Mathahs M, Sowers L, Brown KE, Schmidt WN (2009) Increased plasma nitric oxide, l-arginine, and arginase-1 in cirrhotic patients with progressive renal dysfunction. J Gastroenterol Hepatol 24(6):1030–1037. doi:10.1111/j.1440-1746.2008.05757.x

    Article  CAS  PubMed  Google Scholar 

  • Kim PS, Iyer RK, Lu KV, Yu H, Karimi A, Kern RM, Tai DK, Cederbaum SD, Grody WW (2002) Expression of the liver form of arginase in erythrocytes. Mol Genet Metab 76(2):100–110

    Article  CAS  PubMed  Google Scholar 

  • Kojic J, Robertson PL, Quint DJ, Martin DM, Pang Y, Sundgren PC (2005) Brain glutamine by MRS in a patient with urea cycle disorder and coma. Pediatr Neurol 32(2):143–146. doi:10.1016/j.pediatrneurol.2004.07.013

    Article  PubMed  Google Scholar 

  • Korman SH, Gutman A, Stemmer E, Kay BS, Ben-Neriah Z, Zeigler M (2004) Prenatal diagnosis for arginase deficiency by second-trimester fetal erythrocyte arginase assay and first-trimester ARG1 mutation analysis. Prenat Diagn 24(11):857–860. doi:10.1002/pd.1000

    Article  CAS  PubMed  Google Scholar 

  • Kossel D (1904) Über die Arginase. Z Physiol Chemie 41:321–331

    Article  Google Scholar 

  • Krebs H (1932) Studies on urea formation in the animal organism. Hoppe-Seylers Z Physiol Chem 210:33–66

    Article  CAS  Google Scholar 

  • LaBrecque DR, Latham PS, Riely CA, Hsia YE, Klatskin G (1979) Heritable urea cycle enzyme deficiency-liver disease in 16 patients. J Pediatr 94(4):580–587

    Article  CAS  PubMed  Google Scholar 

  • Lemieux B, Auray-Blais C, Giguere R, Shapcott D, Scriver CR (1988) Newborn urine screening experience with over one million infants in the Quebec Network of Genetic Medicine. J Inherit Metab Dis 11(1):45–55

    Article  CAS  PubMed  Google Scholar 

  • Lonergan ET, Semar M, Sterzel RB, Treser G, Needle MA, Voyles L, Lange K (1971) Erythrocyte transketolase activity in dialyzed patients. A reversible metabolic lesion of uremia. N Engl J Med 284(25):1399–1403. doi:10.1056/NEJM197106242842503

    Article  CAS  PubMed  Google Scholar 

  • Marescau B, Qureshi IA, De Deyn P, Letarte J, Ryba R, Lowenthal A (1985) Guanidino compounds in plasma, urine and cerebrospinal fluid of hyperargininemic patients during therapy. Clinica chimica acta Int J Clin Chem 146(1):21–27

    Article  CAS  Google Scholar 

  • Marescau B, De Deyn PP, Lowenthal A, Qureshi IA, Antonozzi I, Bachmann C, Cederbaum SD, Cerone R, Chamoles N, Colombo JP et al (1990) Guanidino compound analysis as a complementary diagnostic parameter for hyperargininemia: follow-up of guanidino compound levels during therapy. Pediatr Res 27(3):297–303. doi:10.1203/00006450-199003000-00020

    Article  CAS  PubMed  Google Scholar 

  • Martins EG, Silva ES, Vilarinho S, Saudubray JM, Vilarinho L (2010) Neonatal cholestasis: an uncommon presentation of hyperargininemia. J Inherit Metab Dis 33(Suppl 3):S503–S506. doi:10.1007/s10545-010-9263-7

    Article  Google Scholar 

  • Michels VV, Beaudet AL (1978) Arginase deficiency in multiple tissues in argininemia. Clin Genet 13(1):61–67

    Article  CAS  PubMed  Google Scholar 

  • Mizutani N, Hayakawa C, Maehara M, Watanabe K (1987a) Enzyme replacement therapy in a patient with hyperargininemia. Tohoku J Exp Med 151(3):301–307

    Article  CAS  PubMed  Google Scholar 

  • Mizutani N, Hayakawa C, Ohya Y, Watanabe K, Watanabe Y, Mori A (1987b) Guanidino compounds in hyperargininemia. Tohoku J Exp Med 153(3):197–205

    Article  CAS  PubMed  Google Scholar 

  • Mohseni J, Hock CB, Razak CA, Othman SN, Hayati F, Peitee WO, Haniffa M, Zilfalil BA, Mohd Rawi R, Ngu LH, Sasongko TH (2014) Novel complex re-arrangement of ARG1 commonly shared by unrelated patients with hyperargininemia. Gene 533(1):240–245. doi:10.1016/j.gene.2013.09.081

    Article  CAS  PubMed  Google Scholar 

  • Mori T, Nagai K, Mori M, Nagao M, Imamura M, Iijima M, Kobayashi K (2002) Progressive liver fibrosis in late-onset argininosuccinate lyase deficiency. Pediatr Dev Pathol Offi J Soc Pediatr Pathol Paediatr Pathol Soc 5(6):597–601. doi:10.1007/s10024-002-0109-7

    Article  Google Scholar 

  • Morris SM Jr (2007) Arginine metabolism: boundaries of our knowledge. J Nutr 137(6 Suppl 2):1602S–1609S

    CAS  PubMed  Google Scholar 

  • Morris SM Jr, Bhamidipati D, Kepka-Lenhart D (1997) Human type II arginase: sequence analysis and tissue-specific expression. Gene 193(2):157–161

    Article  CAS  PubMed  Google Scholar 

  • Naylor EW (1982) Newborn screening for urea cycle disorders. Adv Exp Med Biol 153:9–18

    Article  CAS  PubMed  Google Scholar 

  • Naylor EW, Cederbaum SD (1981) Urinary pyrimidine excretion in arginase deficiency. J Inherit Metab Dis 4(4):207–210

    Article  CAS  PubMed  Google Scholar 

  • Oldham MS, VanMeter JW, Shattuck KF, Cederbaum SD, Gropman AL (2010) Diffusion tensor imaging in arginase deficiency reveals damage to corticospinal tracts. Pediatr Neurol 42(1):49–52. doi:10.1016/j.pediatrneurol.2009.07.017

    Article  PubMed Central  PubMed  Google Scholar 

  • Picker JD, Puga AC, Levy HL, Marsden D, Shih VE, Degirolami U, Ligon KL, Cederbaum SD, Kern RM, Cox GF (2003) Arginase deficiency with lethal neonatal expression: evidence for the glutamine hypothesis of cerebral edema. J Pediatr 142(3):349–352. doi:10.1067/mpd.2003.97

    Article  PubMed  Google Scholar 

  • Prasad AN, Breen JC, Ampola MG, Rosman NP (1997) Argininemia: a treatable genetic cause of progressive spastic diplegia simulating cerebral palsy: case reports and literature review. J Child Neurol 12(5):301–309

    Article  CAS  PubMed  Google Scholar 

  • Prast H, Philippu A (2001) Nitric oxide as modulator of neuronal function. Prog Neurobiol 64(1):51–68

    Article  CAS  PubMed  Google Scholar 

  • Qureshi IA, Letarte J, Ouellet R, Lelievre M, Laberge C (1981) Ammonia metabolism in a family affected by hyperargininemia. Diabete Metab 7(1):5–11

    CAS  PubMed  Google Scholar 

  • Qureshi IA, Letarte J, Ouellet R, Larochelle J, Lemieux B (1983) A new French-Canadian family affected by hyperargininaemia. J Inherit Metab Dis 6(4):179–182

    Article  CAS  PubMed  Google Scholar 

  • Qureshi IA, Letarte J, Ouellet R, Batshaw ML, Brusilow S (1984) Treatment of hyperargininemia with sodium benzoate and arginine-restricted diet. J Pediatr 104(3):473–476

    Article  CAS  PubMed  Google Scholar 

  • Rashed MS, Rahbeeni Z, Ozand PT (1999) Application of electrospray tandem mass spectrometry to neonatal screening. Semin Perinatol 23(2):183–193

    Article  CAS  PubMed  Google Scholar 

  • Rovira A, Alonso J, Cordoba J (2008) MR imaging findings in hepatic encephalopathy. AJNR Am J Neuroradiol 29(9):1612–1621. doi:10.3174/ajnr.A1139

    Article  CAS  PubMed  Google Scholar 

  • Saheki T, Kobayashi K, Iijima M, Horiuchi M, Begum L, Jalil MA, Li MX, Lu YB, Ushikai M, Tabata A, Moriyama M, Hsiao KJ, Yang Y (2004) Adult-onset type II citrullinemia and idiopathic neonatal hepatitis caused by citrin deficiency: involvement of the aspartate glutamate carrier for urea synthesis and maintenance of the urea cycle. Mol Genet Metab 81(Suppl 1):S20–S26. doi:10.1016/j.ymgme.2004.01.006

    Article  CAS  PubMed  Google Scholar 

  • Sakiyama T, Nakabayashi H, Shimizu H, Kondo W, Kodama S, Kitagawa T (1984) A successful trial of enzyme replacement therapy in a case of argininemia. Tohoku J Exp Med 142(3):239–248

    Article  CAS  PubMed  Google Scholar 

  • Scaglia F, Lee B (2006) Clinical, biochemical, and molecular spectrum of hyperargininemia due to arginase I deficiency. Am J Med Genet Part C Sem Med Genet 142C(2):113–120. doi:10.1002/ajmg.c.30091

    Article  CAS  Google Scholar 

  • Scheuerle AE, McVie R, Beaudet AL, Shapira SK (1993) Arginase deficiency presenting as cerebral palsy. Pediatrics 91(5):995–996

    CAS  PubMed  Google Scholar 

  • Schiff M, Benoist JF, Cardoso ML, Elmaleh-Berges M, Forey P, Santiago J, Ogier de Baulny H (2009) Early-onset hyperargininaemia: a severe disorder? J Inherit Metab Dis 32(Suppl 1):S175–S178. doi:10.1007/s10545-009-1137-5

    Article  PubMed  Google Scholar 

  • Schulze A, Ebinger F, Rating D, Mayatepek E (2001) Improving treatment of guanidinoacetate methyltransferase deficiency: reduction of guanidinoacetic acid in body fluids by arginine restriction and ornithine supplementation. Mol Genet Metab 74(4):413–419. doi:10.1006/mgme.2001.3257

    Article  CAS  PubMed  Google Scholar 

  • Segawa Y, Matsufuji M, Itokazu N, Utsunomiya H, Watanabe Y, Yoshino M, Takashima S (2011) A long-term survival case of arginase deficiency with severe multicystic white matter and compound mutations. Brain Dev 33(1):45–48. doi:10.1016/j.braindev.2010.03.001

    Article  PubMed  Google Scholar 

  • Shearer JD, Richards JR, Mills CD, Caldwell MD (1997) Differential regulation of macrophage arginine metabolism: a proposed role in wound healing. Am J Physiol 272(2 Pt 1):E181–E190

    CAS  PubMed  Google Scholar 

  • Silva ES, Martins E, Cardoso ML, Barbot C, Vilarinho L, Medina M (2001) Liver transplantation in a case of argininaemia. J Inherit Metab Dis 24(8):885–887

    Article  Google Scholar 

  • Silva ES, Cardoso ML, Vilarinho L, Medina M, Barbot C, Martins E (2013) Liver transplantation prevents progressive neurological impairment in argininemia. JIMD Rep 11:25–30. doi:10.1007/8904_2013_218

    Article  PubMed Central  PubMed  Google Scholar 

  • Snyderman SE, Sansaricq C, Norton PM, Goldstein F (1979) Argininemia treated from birth. J Pediatr 95(1):61–63

    Article  CAS  PubMed  Google Scholar 

  • Sparkes RS, Dizikes GJ, Klisak I, Grody WW, Mohandas T, Heinzmann C, Zollman S, Lusis AJ, Cederbaum SD (1986) The gene for human liver arginase (ARG1) is assigned to chromosome band 6q23. Am J Hum Genet 39(2):186–193

    PubMed Central  CAS  PubMed  Google Scholar 

  • Spector EB, Kiernan M, Bernard B, Cederbaum SD (1980) Properties of fetal and adult red blood cell arginase: a possible prenatal diagnostic test for arginase deficiency. Am J Hum Genet 32(1):79–87

    PubMed Central  CAS  PubMed  Google Scholar 

  • Spector EB, Rice SC, Cederbaum SD (1983) Immunologic studies of arginase in tissues of normal human adult and arginase-deficient patients. Pediatr Res 17(12):941–944

    Article  CAS  PubMed  Google Scholar 

  • Steiner RD, Cederbaum SD (2001) Laboratory evaluation of urea cycle disorders. J Pediatr 138(1 Suppl):S21–S29

    Article  CAS  PubMed  Google Scholar 

  • Stockler-Ipsiroglu S, van Karnebeek C, Longo N, Korenke GC, Mercimek-Mahmutoglu S, Marquart I, Barshop B, Grolik C, Schlune A, Angle B, Araujo HC, Coskun T, Diogo L, Geraghty M, Haliloglu G, Konstantopoulou V, Leuzzi V, Levtova A, Mackenzie J, Maranda B, Mhanni AA, Mitchell G, Morris A, Newlove T, Renaud D, Scaglia F, Valayannopoulos V, van Spronsen FJ, Verbruggen KT, Yuskiv N, Nyhan W, Schulze A (2014) Guanidinoacetate methyltransferase (GAMT) deficiency: outcomes in 48 individuals and recommendations for diagnosis, treatment and monitoring. Mol Genet Metab 111(1):16–25. doi:10.1016/j.ymgme.2013.10.018

    Article  CAS  PubMed  Google Scholar 

  • Summar ML, Koelker S, Freedenberg D, Le Mons C, Haberle J, Lee HS, Kirmse B, European R, Network for Intoxication Type Metabolic Diseases. Electronic address hwe-ioeip, Members of the Urea Cycle Disorders Consortium. Electronic address hreueu (2013) The incidence of urea cycle disorders. Mol Genet Metab 110(1–2):179–180. doi:10.1016/j.ymgme.2013.07.008

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Terheggen SA, Lowenthal A, van Sande M, Colombo P (1969) Argininaemia with Arginase Deficiency. Lancet 294:748–749

    Article  Google Scholar 

  • Terheggen HG, Schwenk A, Lowenthal A, van Sande M, Colombo JP (1970a) Hyperargininemia with arginase deficiency. A new familial metabolic disease. II. Biochemical studies. Zeitschrift fur Kinderheilkunde 107(4):313–323

  • Terheggen HG, Schwenk A, Lowenthal A, van Sande M, Colombo JP (1970b) Hyperargininemia wityh arginase deficiency. A new familial metabolic disease. I. Clinical studies. Zeitschrift fur Kinderheilkunde 107(4):298–312

  • Terheggen HG, Lowenthal A, Lavinha F, Colombo JP (1975) Familial hyperargininaemia. Arch Dis Child 50(1):57–62

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Terheggen HG, Lowenthal A, Colombo JP (1982) Clinical and biochemical findings in argininemia. Adv Exp Med Biol 153:111–119

    Article  CAS  PubMed  Google Scholar 

  • Tomlinson S, Westall RG (1964) Argininosuccinic Aciduria. Argininosuccinase and arginase in human blood cells. Clin Sci 26:261–269

    CAS  PubMed  Google Scholar 

  • Tsang JP, Poon WL, Luk HM, Fung CW, Ching CK, Mak CM, Lam CW, Siu TS, Tam S, Wong VC (2012) Arginase deficiency with new phenotype and a novel mutation: contemporary summary. Pediatr Neurol 47(4):263–269. doi:10.1016/j.pediatrneurol.2012.06.012

    Article  PubMed  Google Scholar 

  • Uchino T, Snyderman SE, Lambert M, Qureshi IA, Shapira SK, Sansaricq C, Smit LM, Jakobs C, Matsuda I (1995) Molecular basis of phenotypic variation in patients with argininemia. Hum Genet 96(3):255–260

    Article  CAS  PubMed  Google Scholar 

  • Virarkar M, Alappat L, Bradford PG, Awad AB (2013) l-arginine and nitric oxide in CNS function and neurodegenerative diseases. Crit Rev Food Sci Nutr 53(11):1157–1167. doi:10.1080/10408398.2011.573885

    Article  CAS  PubMed  Google Scholar 

  • Vockley JG, Tabor DE, Kern RM, Goodman BK, Wissmann PB, Kang DS, Grody WW, Cederbaum SD (1994) Identification of mutations (D128G, H141L) in the liver arginase gene of patients with hyperargininemia. Hum Mutat 4(2):150–154. doi:10.1002/humu.1380040210

    Article  CAS  PubMed  Google Scholar 

  • Vockley JG, Goodman BK, Tabor DE, Kern RM, Jenkinson CP, Grody WW, Cederbaum SD (1996) Loss of function mutations in conserved regions of the human arginase I gene. Biochem Mol Med 59(1):44–51

    Article  CAS  PubMed  Google Scholar 

  • Whitington PF, Alonso EM, Boyle JT, Molleston JP, Rosenthal P, Emond JC, Millis JM (1998) Liver transplantation for the treatment of urea cycle disorders. J Inherit Metab Dis 21(Suppl 1):112–118

    Article  PubMed  Google Scholar 

  • Wiechert P, Marescau B, De Deyn PP, Lowenthal A (1989) Hyperargininemia, epilepsy and the metabolism of guanidino compounds. Padiatrie und Grenzgebiete 28(2):101–106

    CAS  PubMed  Google Scholar 

  • Wu G, Morris SM Jr (1998) Arginine metabolism: nitric oxide and beyond. Biochem J 336(Pt 1):1–17

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Wu TF, Liu YP, Li XY, Wang Q, Ding Y, Ma YY, Song JQ, Yang YL (2013) Five novel mutations in ARG1 gene in Chinese patients of argininemia. Pediatr Neurol 49(2):119–123. doi:10.1016/j.pediatrneurol.2013.04.026

    Article  PubMed  Google Scholar 

  • Wyse AT, Bavaresco CS, Hagen ME, Delwing D, Wannmacher CM, Severo Dutra-Filho C, Wajner M (2001) In vitro stimulation of oxidative stress in cerebral cortex of rats by the guanidino compounds accumulating in hyperargininemia. Brain Res 923(1–2):50–57

    Article  CAS  PubMed  Google Scholar 

  • Wyse AT, Stefanello FM, Chiarani F, Delwing D, Wannmacher CM, Wajner M (2004) Arginine administration decreases cerebral cortex acetylcholinesterase and serum butyrylcholinesterase probably by oxidative stress induction. Neurochem Res 29(2):385–389

    Article  CAS  PubMed  Google Scholar 

  • Yang Z, Ming XF (2014) Functions of arginase isoforms in macrophage inflammatory responses: impact on cardiovascular diseases and metabolic disorders. Front Immunol 5:533. doi:10.3389/fimmu.2014.00533

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Zhang Y, Landau YE, Miller DT, Marsden D, Berry GT, Kellogg MD (2012) Recurrent unexplained hyperammonemia in an adolescent with arginase deficiency. Clin Biochem 45(18):1583–1586. doi:10.1016/j.clinbiochem.2012.08.015

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children’s Hospital, Heinrich Heine University, Moorenstr. 5, 40225, Düsseldorf, Germany

    A. Schlune, R. Ensenauer & E. Mayatepek

  2. Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital, Heinrich Heine University, Moorenstr. 5, 40225, Düsseldorf, Germany

    S. vom Dahl & D. Häussinger

Authors
  1. A. Schlune
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. vom Dahl
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. Häussinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R. Ensenauer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. E. Mayatepek
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. Schlune.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Schlune, A., vom Dahl, S., Häussinger, D. et al. Hyperargininemia due to arginase I deficiency: the original patients and their natural history, and a review of the literature. Amino Acids 47, 1751–1762 (2015). https://doi.org/10.1007/s00726-015-2032-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00726-015-2032-z

Keywords

Search

Navigation