Hyperammonemia in review: Pathophysiology, diagnosis, and treatment

Pediatric Nephrology

Volumn 27, Issue 2, 2012, Pages 207-222

  Auron, Ari ^a   Brophy, Patrick D ^b  

^a Blank Memorial Hospital for Children   (United States)

^b UNIVERSITY OF IOWA CHILDREN S HOSPITAL   (United States)

Author keywords

Dialysis; Hyperammonemia; Pathophysiology; Treatment; Urea cycle defects

Indexed keywords

AMMONIA; ARGININE; BENZOIC ACID; CALCIUM; CARBAMAZEPINE; CARNITINE; CHOLINE ACETYLTRANSFERASE; CILIARY NEUROTROPHIC FACTOR; CITRULLINE; GLUTAMIC ACID; GLUTAMINE; HYPOGLYCINE A; PHENYLACETIC ACID; POTASSIUM; SALICYLIC ACID; TOPIRAMATE; TRANEXAMIC ACID; TRYPTOPHAN; VALPROIC ACID;

ARGININOSUCCINIC ACIDURIA; BASAL GANGLION; BIOSYNTHESIS; BRAIN ATROPHY; BRAIN HEMORRHAGE; BRAIN VENTRICLE DILATATION; CANCER CHEMOTHERAPY; CARBAMOYL PHOSPHATE SYNTHETASE I DEFICIENCY; CENTRAL NERVOUS SYSTEM DISEASE; CITRULLINEMIA; DIALYSIS; DIFFERENTIAL DIAGNOSIS; ENERGY; ENZYME INDUCTION; GLIOSIS; HEPATIC ENCEPHALOPATHY; HUMAN; HYPERAMMONEMIA; HYPERARGININEMIA; KIDNEY TUBULE ACIDOSIS; LIVER TRANSPLANTATION; MAPLE SYRUP URINE DISEASE; METHYLMALONIC ACIDEMIA; NEUROPROTECTION; NEUROTRANSMISSION; NONHUMAN; NUTRIENT SUPPLY; ORNITHINE TRANSCARBAMYLASE DEFICIENCY; PATHOPHYSIOLOGY; PREGNANCY; PRIORITY JOURNAL; REVIEW; REYE SYNDROME; UREA CYCLE DISORDER;

AMINO ACIDS; ARGININOSUCCINIC ACIDURIA; BRAIN; CITRULLINEMIA; DIAGNOSIS, DIFFERENTIAL; HUMANS; HYPERAMMONEMIA; SYNAPTIC TRANSMISSION; UREA CYCLE DISORDERS, INBORN;

EID: 84857115848     PISSN: 0931041X     EISSN: 1432198X     Source Type: Journal    
DOI: 10.1007/s00467-011-1838-5     Document Type: Review

References (109)

1. Walker V (2009) Ammonia toxicity and its prevention in inherited defects of the urea cycle. Diab Obes Metab 1(9):823-385
2. Tizianello A, Deferrari G, Garibotto G, Robaudo C, Acquarone N, Ghiggeri GM (1982) Renal ammoniagenesis in an early stage of metabolic acidosis in man. J Clin Invest 69(1):240-250 (Pubitemid 12212265)
3. Windmueller HG, Spaeth AE (1980) Respiratory fuels and nitrogen metabolism in vivo in small intestine of fed rats. J Biol Chem 255:107-112
4. Singh RH (2007) Nutritional management of patients with urea cycle disorders. J Inherit Metab Dis 30:880-887 (Pubitemid 50004985)
5. Cooper AJ, Plum P (1987) Biochemistry and physiology of brain ammonia. Physiol Rev 67:440-519 (Pubitemid 17063608)
6. Batshaw ML (1984) Hyperammonemia. Curr Probl Pediatr 14 (11):1-69
7. Schlienger JL, Imler M (1978) Effect of hyperammonemia on insulin-mediated glucose uptake in rats. Metabolism 27(2):175-183 (Pubitemid 8280301)
8. Gropman AL, Summar M, Leonard JV (2007) Neurological implications of urea cycle disorders. J Inherit Metab Dis 30:865-869
9. Enns GM (2008) Neurologic damage and neurocognitive dysfunction in urea cycle disorders. Semin Pediatr Neurol 15:132-139
10. Msall M, Batshaw ML, Suss R, Brusilow SW, Mellits ED (1984) Neurologic outcome in children with inborn errors of urea synthesis. Outcome of ureacycle enzymopathies. N Engl J Med 7 (310 (23)):1500-1505 (Pubitemid 14108846)
11. Enns GM, Berry SA, Berry GT, Rhead WJ, Brusilow SW, Hamosh A (2007) Survival after Treatment with Phenylacetate and Benzoate for Urea-Cycle Disorders. N Engl J Med 356:2282-2292 (Pubitemid 46849158)
12. Butterworth RF (1998) Effects of hyperammonaemia on brain function. J Inherit Metab Dis 21(suppl 1):6-20
13. Pela I, Seracini D, Donati MA, Lavoratti G, Pasquini E, Materassi M (2008) Peritoneal dialysis in neonates with inborn errors of metabolism: Is it really out of date? Pediatr Nephrol 23 (1):163-168 (Pubitemid 350245986)
14. Msall M, Monahan PS, Chapanis N, Batshaw ML (1988) Cognitive development in children with inborn errors of urea synthesis. Acta Paediatr Jpn 30:435-441
15. Strauss KA, Puffenberger EG, Morton DH (2009) Maple Syrup Urine Disease. In: Pagon RA, Bird TC, Dolan CR, Stephens K, eds. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2006 Jan 30 [updated 2009 Dec 15]
16. Bunchman TE, Barletta GM, Winters JW, Gardner JJ, Crumb TL, McBryde KD (2007) Phenylacetate and benzoate clearance in a hyperammonemic infant on sequential hemodialysis and hemofiltration. Pediatr Nephrol 22:1062-1065 (Pubitemid 46881929)
17. Braissant O (2010) Current concepts in the pathogenesis of urea cycle disorders. Mol Genet Metab 100(Suppl 1):S3-S12
18. Takanashi J, Barkovich AJ, Cheng SF, Weisiger K, Zlatunich CO, Mudge C, Rosenthal P, Tuchman M, Packman S (2003) Brain MR imaging in neonatal hyperammonemic encephalopathy resulting from proximal urea cycle disorders. Am J Neuroradiol 24:1184-1187 (Pubitemid 36734248)
19. Filloux F, Townsend JJ, Leonard C (1986) Ornithine transcarbamylase deficiency: Neuropathologic changes acquired in utero. J Pediatr 108:942-945 (Pubitemid 16096817)
20. Connelly A, Cross JH, Gadian DG, Hunter JV, Kirkham FJ, Leonard JV (1993) Magnetic resonance spectroscopy shows increased brain glutamine in ornithine carbamoyl transferase deficiency. Pediatr Res 33:77-81 (Pubitemid 23094131)
21. Cooper AJ (2001) Role of glutamine in cerebral nitrogen metabolism and ammonia neurotoxicity. Ment Retard Dev Disabil Res Rev 7:280-286 (Pubitemid 33108267)
22. Heins J, Zwingmann C (2010) Organic osmolytes in hyponatremia and ammonia toxicity. Metab Brain Dis 25(1):81-89
23. Scaglia F, Brunetti-Pierri N, Kleppe S,Marini J, Carter S, Garlick P, Jahoor F, O'Brien W, Lee B (2004) Clinical consequences of urea cycle enzyme deficiencies and potential links to arginine and nitric oxide metabolism. J Nutr 134:2775S-2782S (Pubitemid 39315220)
24. Inoue I, Gushiken T, Kobayashi K, Saheki T (1987) Accumulation of large neutral amino acids in the brain of sparse-fur mice at hyperammonemic state. Biochem Med Metab Biol 38:378-386
25. Batshaw ML, Robinson MB, Hyland K, Djali S, Heyes MP (1993) Quinolinic acid in children with congenital hyperammonemia. Ann Neurol 34:676-681 (Pubitemid 23333239)
26. Rodrigo R, Cauli O, Boix J, El Mlili N, Agusti A, Felipo V (2009) Role of NMDA receptors in acute liver failure and ammonia toxicity: Therapeutical implications. Neurochem Int 55:113-118
27. Schwarcz R, Köhler C (1983) Differential vulnerability of central neurons of the rat to quinolinic acid. Neurosci Lett 38:85-90 (Pubitemid 13029108)
28. Rose C (2006) Effect of ammonia on astrocytic glutamate uptake/release mechanisms. J Neurochem 97(suppl 1):11-15
29. Rao KV, Qureshi IA (1999) Reduction in the MK-801 binding sites of the NMDA sub-type of glutamate receptor in a mouse model of congenital hyperammonemia: Prevention by acetyl-Lcarnitine. Neuropharmacology 38:383-394 (Pubitemid 29097721)
30. Cauli O, Rodrigo R, Llansola M, Montoliu C, Monfort P, Piedrafita B, El Mlili N, Boix J, Agusti A, Felipo V (2009) Glutamatergic and gabaergic neurotransmission and neuronal circuits in hepatic encephalopathy. Metab Brain Dis 24:69-80
31. Ratnakumari L, Qureshi IA, Butterworth RF (1994) Evidence for cholinergic neuronal loss in brain in congenital ornithine transcarbamylase deficiency. Neurosci Lett 178:63-65
32. Robinson MB, Anegawa NJ, Gorry E, Qureshi IA, Coyle JT, Lucki I, Batshaw ML (1992) Brain serotonin 2 and serotonin 1A receptors are altered in the congenitally hyperammonemic sparse fur mouse. J Neurochem 58:1016-1022
33. Bachmann C, Colombo JP (1984) Increase of tryptophan and 5- hydroxyindole acetic acid in the brain of ornithine carbamoyltransferase deficient sparse-fur mice. Pediatr Res 18:372-375 (Pubitemid 14134229)
34. Hyman SL, Coyle JT, Parke JC, Porter C, Thomas GH, Jankel W, Batshaw ML (1986) Anorexia and altered serotonin metabolism in a patient with argininosuccinic aciduria. J Pediatr 108:705-709 (Pubitemid 16064114)
35. Rao KV, Mawal YR, Qureshi IA (1997) Progressive decrease of cerebral cytochrome C oxidase activity in sparse-fur mice: Role of acetyl-L-carnitine in restoring the ammonia-induced cerebral energy depletion. Neurosci Lett 224:83-86 (Pubitemid 27122176)
36. Zanelli SA, Solenski NJ, Rosenthal RE, Fiskum G (2005) Mechanisms of ischemic neuroprotection by acetyl-L-carnitine. Ann NY Acad Sci 1053:153-161 (Pubitemid 43031093)
37. Braissant O, Cagnon L, Monnet-Tschudi F, Speer O, Wallimann T, Honegger P, Henry H (2008) Ammonium alters creatine transport and synthesis in a 3D-culture of developing brain cells, resulting in secondary cerebral creatine deficiency. Eur J Neurosci 27:1673-1685 (Pubitemid 351473571)
38. Braissant O, Henry H, Villard AM, Zurich MG, Loup M, Eilers B, Parlascino G, Matter E, Boulat O, Honegger P, Bachmann C (2002) Ammonium induced impairment of axonal growth is prevented through glial creatine. J Neurosci 22:9810-9820 (Pubitemid 35332865)
39. Cagnon L, Braissant O (2009) CNTF protects oligodendrocytes from ammonia toxicity: Intracellular signaling pathways involved. Neurobiol Dis 33:133-142
40. Jayakumar AR, Panickar KS, Murthy C, Norenberg MD (2006) Oxidative stress and mitogen-activated protein kinase phosphorylation mediate ammonia induced cell swelling and glutamate uptake inhibition in cultured astrocytes. J Neurosci 26:4774-4784 (Pubitemid 44315317)
41. Lichter-Konecki U, Mangin JM, Gordish-Dressman H, Hoffman EP, Gallo V (2008) Gene expression profiling of astrocytes from hyperammonemic mice reveals altered pathways for water and potassium homeostasis in vivo. Glia 56:365-377 (Pubitemid 351212946)
42. Bosoi CR, Rose CF (2009) Identifying the direct effects of ammonia on the brain. Metab Brain Dis 24(1):95-102
43. Walters S, Brophy PD (2009) Inborn errors of metabolism and continuous renal replacement therapy. In: Ronco C, Bellomo R, Kellum J (eds) Critical care nephrology, 2nd edn. Elsevier, Oxford, pp 1630-1633
44. Tuchman M, Lee B, Lichter-Konecki U, Summar ML, Yudkoff M, Cederbaum SD, Kerr DS, Diaz GA, Seashore MR, Lee HS, McCarter RJ, Krischer JP, Batshaw ML (2008) Cross-sectional multicenter study of patients with urea cycle disorders in the United States. Mol Genet Metab 94:397-402
45. Summar ML (2005) Urea Cycle Disorders Overview. In: Pagon RA, Bird TC, Dolan CR, Stephens K, eds. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2003 Apr 29 [updated 2005 Aug 11]
46. Lo WD, Sloan HR, Sotos JF, Klinger RJ (1993) Late Clinical Presentation of Partial Carbamyl Phosphate Synthetase I Deficiency. Am J Dis Child 147(3):267-269 (Pubitemid 23077281)
47. Arranz JA, Riudor E, Marco-Marín C, Rubio V (2007) Estimation of the total number of disease-causing mutations in ornithine transcarbamylase (OTC) deficiency Value of the OTC structure in predicting a mutation pathogenic potential. J Inherit Metab Dis 30(2):217-226 (Pubitemid 46488004)
48. Brusilow SW, Maestri NE (1996) Urea cycle disorders: Diagnosis, pathophysiology, and therapy. Adv Pediatr 43:127-170
49. Rajantie J, Simell O, Perheentupa J (1981) Lysinuric protein intolerance: Basolateral transport effect in renal tubuli. J Clin Invest 67:1078-1082 (Pubitemid 11090547)
50. Adams EN, Marks A, Lizer MH (2009) Carbamazepine-induced hyperammonemia. Am J Health Syst Pharm 66(16):1468-1470
51. Ambrosetto G, Riva R, Baruzzi A (1984) Hyperammonemia in asterixis induced by carbamazepine: Two case reports. Acta Neurol Scand 69:186-189 (Pubitemid 14155923)
52. Rivelli M, El-Mallakh RS, Nelson WH (1988) Carbamazepineassociated asterixis and hyperammonemia. Am J Psychiatry 145:269-270
53. Segura-Bruna N, Rodriguez-Campello A, Puente V, Roquer J (2006) Valproate-induced hyperammonemic encephalopathy. Acta Neurol Scand 114:1-7 (Pubitemid 43873517)
54. Raskind JY, El-Chaar GM (2000) The role of carnitine supplementation during valproic acid therapy. Ann Pharmacother 34:630-638 (Pubitemid 30257492)
55. Deutsch SI, Burket JA, Rosse RB (2009) Valproate-induced hyperammonemic encephalopathy and normal liver functions: Possible synergism with topiramate. Clin Neuropharmacol 32 (6):350-352
56. Kamoun P, Rabier D (1987) Valproate induced inhibition of urea synthesis. Lancet 1:48
57. Hamer HM, Knake S, Schomburg U, Rosenow F (2000) Valproate-induced hyperammonemic encephalopathy in the presence of topiramate. Neurology 54:230-232 (Pubitemid 30038768)
58. Knudsen JF, Sokol GH, Flowers CM (2008) Adjunctive topiramate enhances the risk of hypothermia associated with valproic acid therapy. J Clin Pharm Ther 33:513-519
59. Wang CS, Yang CJ, Chen SC, Chen HC, Huang MS (2009) Generalized convulsion resulted in hyperammonemia during treatment with tranexamic acid for hemoptysis.Ir J Med Sci doi:10.1007/s11845-009-0453-y
60. Jaing TH, Lin JL, Lin YP, Yang SH, Lin JJ, Hsia SH (2009) Hyperammonemic Encephalopathy After Induction Chemotherapy for Acute Lymphoblastic Leukemia. J Pediatr Hematol Oncol 31(12):955-956
61. Nott L, Price TJ, Pittman K, Patterson K, Young R, Fletcher J (2007) Hyperammonemia encephalopathy: An important cause of neurological deterioration following chemotherapy. Leuk Lymphoma 48:1702-1711 (Pubitemid 47386705)
62. Metzeler KH, Boeck S, Christ B, Hausmann A, Stemmler HJ, Parhofer KG, Ostermann H, Hiddemann W, Braess J (2009) Idiopathic hyperammonemia (IHA) after dose-dense induction chemotherapy for acute myeloid leukemia: Case report and review of the literature. Leuk Res 33(7):e69-e72
63. Kwan L, Wang C, Levitt L (2002) Hyperammonemic encephalopathy in multiple myeloma. N Eng J Med 346:1674-1675
64. Liaw CC, Wang HM, Wang CH, Yang TS, Chen JS, Chang HK, Lin YC, Liaw SJ, Yeh CT (1999) Risk of transient hyperammonemic encephalopathy in cancer patients who received continuous infusion of 5-fluorouracil with the complication of dehydration and infection. Anticancer Drugs 10:275-281
65. Nott L, Price TJ, Pittman K, Patterson K, Young R, Fletcher J (2008) Hyperammonemic encephalopathy associated with rituximab-containing chemotherapy. Intern Med J 38(10):800-803
66. Tihtonen K, Uotila J, Lähde J, Salo M, Keskinen P (2010) Risk of hyperammonemic coma in the puerperium: Two cases of women with diagnosed and undiagnosed deficiency of urea cycle enzymes. Acta Obstet Gynecol Scand 89(3):404-406
67. Cordero D, Baker J, Dorinzi D, Toffle R (2005) Ornithine transcarbamylase deficiency in pregnancy. J Inherit Metab Dis 28:237-240 (Pubitemid 40723891)
68. Eather G, Coman D, Lander C, McGill J (2006) Carbamyl phosphate synthase deficiency: Diagnosed during pregnancy in a 41-year-old. J Clin Neurosci 13:702-706 (Pubitemid 44066806)
69. Seracini D, Poggi GM, Pela I (2005) Hyperammonaemia in a child with distal renal tubular acidosis. Pediatr Nephrol 20:1645-1647 (Pubitemid 41554481)
70. Tannen RL (1977) Relationship of renal ammonia production and potassium homeostasis. Kidney Int 11(6):453-465 (Pubitemid 8129230)
71. Miller SG, Schwartz GJ (1997) Hyperammonemia with distal renal tubular acidosis. Arch Dis Child 77:441-444 (Pubitemid 27521530)
72. Limketkai BN, Zucker SD (2008) Hyperammonemic Encephalopathy Caused by Carnitine Deficiency. J Gen Intern Med 23 (2):210-213
73. Samtoy B, DeBeukelaer MM (1980) Ammonia encephalopathy secondary to urinary tract infection with Proteus mirabilis. Pediatrics 65(2):294-297 (Pubitemid 10068590)
74. Ichikawa K, Gakumazawa M, Inaba A, Shiga K, Takeshita S, Mori M, Kikuchi N (2010) Acute encephalopathy of Bacillus cereus mimicking Reye syndrome. Brain 32(8):688-690
75. Picca S, Bartuli A, Dionisi-Vici C (2008) Medical Management and Dialysis Therapy for the Infant With an Inborn Error of Metabolism. Semin Nephrol 28:477-480
76. Summar M (2001) Current strategies for the management of neonatal urea cycle disorders. J Pediatr 138:S30-S39 (Pubitemid 32099501)
77. Ogier de Baulny H (2002) Management and emergency treatments of neonates with a suspicion of inborn errors of metabolism. Semin Neonatol 7:17-26 (Pubitemid 34742216)
78. Schwahn BC, Pieterse L, Bisset WM, Galloway PG, Robinson PH (2010) Biochemical efficacy of N-carbamylglutamate in neonatal severe hyperammonaemia due to propionic acidaemia. Eur J Pediatr 169(1):133-134
79. Kalkan Ucar S, Coker M, Habif S, Ulas Saz E, Karapinar B, Ucar H, Kitis O, Duran M (2009) The first use of Ncarbamylglutamate in a patient with decompensated maple syrup urine disease. Metab Brain Dis 24(3):409-414
80. Filippi L, Gozzini E, Fiorini P, Malvagia S, la Marca G, Donati MA (2010) N-carbamylglutamate in emergency management of hyperammonemia in neonatal acute onset propionic and methylmalonic aciduria. Neonatology 97(3):286-290
81. Gebhardt B, Vlaho S, Fischer D, Sewell A, Bohles H (2003) Ncarbamyl glutamate enhances ammonia detoxification in a patient with decompensated methylmalonic aciduria. Mol Genet Metab 79:303-304 (Pubitemid 37013540)
82. Gessler P, Buchal P, Schwenk HU, Wermuth B (2010) Favorable long-term outcome after immediate treatment of neonatal hyperammonemia due to N-acetylglutamate synthase deficiency. Eur J Pediatr 169:197-199
83. Batshaw ML, Brusilow SW (1980) Treatment of hyperammonemic coma caused by inborn errors of urea synthesis. J Pediatr 97:893-900 (Pubitemid 11209365)
84. Willard-Mack CL, Koehler RC, Hirata T, Cork LC, Takahashi H, Traystman RJ, Brusilow SW (1996) Inhibition of glutamine synthetase reduces ammonia-induced astrocyte swelling in rat. Neuroscience 71:589-599 (Pubitemid 26067021)
85. Das AM, Illsinger S, Hartmann H, Oehler K, Bohnhorst B, Kühn-Velten WN, Lücke T (2009) Prenatal benzoate treatment in urea cycle defects. Arch Dis Child Fetal Neonatal Ed 94(3): F216-F217
86. Brusilow SW (1984) Arginine, an indispensable amino acid for patients with inborn errors of urea synthesis. J Clin Invest 74:2144-2148 (Pubitemid 15197359)
87. Batshaw ML, MacArthur RB, Tuchman M (2001) Alternative pathway therapy for urea cycle disorders: Twenty years later. J Pediatr 138(Suppl):S46-S55 (Pubitemid 32099503)
88. Arbeiter AK, Kranz B, Wingen Bonzel KE, Dohna AM, - Schwake C, Hanssler L, Neudorf U, Hoyer PF, Büscher R (2010) ontinuous venovenous haemodialysis (CVVHD) and continuous peritoneal dialysis (CPD) in the acute management of 21 children with inborn errors of metabolism. Nephrol Dial Transplant 25:1257-1265
89. Schaefer F, Straube E, Oh J, Mehls O, Mayatepek E (1999) Dialysis in neonates with inborn errors of metabolism. Nephrol Dial Transplant 14:910-918 (Pubitemid 29155146)
90. Wong KY, Wong SN, Lam SY, Tam S, Tsoi NS (1998) Ammonia clearance by peritoneal dialysis and continuous arteriovenous hemodiafiltration. Pediatr Nephrol 12:589-591 (Pubitemid 28408233)
91. Picca S, Dionisi-Vici C, Abeni D, Pastore A, Rizzo C, Orzalesi M, Sabetta G, Rizzoni G, Bartuli A (2001) Extracorporeal dialysis in neonatal hyperammonemia: Modalities and prognostic indicators. Pediatr Nephrol 16:862-867 (Pubitemid 33040642)
92. Rajpoot DK, Gargus JJ (2004) Acute hemodialysis for hyperammonemia in small neonates. Pediatr Nephrol 19(4):390-395 (Pubitemid 38477401)
93. McBryde KD, Kudelka TL, Kershaw DB, Brophy PD, Gardner JJ, Smoyer WE (2004) Clearance of amino acids by hemodialysis in argininosuccinate synthetase deficiency. J Pediatr 144:536-540 (Pubitemid 38457362)
94. Sadowski RH, Harmon EH, Jabs K (1994) Acute hemodialysis of infants weighing less than five kilograms. Kidney Int 45:903-906 (Pubitemid 24094506)
95. Donn SM, Swartz RD, Thoene JG (1979) Comparison of exchange transfusion, peritoneal dialysis, and hemodialysis for the treatment of hyperammonemia in an anuric newborn infant. J Pediatr 95(1):67-70 (Pubitemid 9183677)
96. Goertner L, Leupold D, Pohlandt F, Bartmann P (1989) Peritoneal dialysis in the treatment of metabolic crises caused by inherited disorders of organic and amino acid metabolism. Acta Paediatr Scand 78:706-711 (Pubitemid 19232305)
97. Ponikvar R, Kandus A, Urbancic A, Kornhauser AG, Primozic J, Ponikvar JG (2002) Continuous renal replacement therapy and plasma exchange in newborns and infants. Artif Organs 26:163-168 (Pubitemid 34225214)
98. Falk MC, Knight JF, Roy LP, Wilcken B, Schell DN, O'Connell AJ, Gillis J (1994) Continuous venovenous haemofiltration in the acute treatment of inborn errors of metabolism. Pediatr Nephrol 8(3):330-333 (Pubitemid 24162274)
99. Parakininkas D, Greenbaum LA (2004) Comparison of solute clearance in three modes of continuous renal replacement therapy. Pediatr Crit Care Med 5(3):269-274
100. Rodrigo R, Cauli O, Boix J, ElMlili N, Agusti A, Felipo V (2009) Role of NMDA receptors in acute liver failure and ammonia toxicity: Therapeutical implications. Neurochem Int 55 (1-3):113-118
101. Acharya SK, Bhatia V, Sreenivas V, Khanal S, Panda SK (2009) Efficacy of L-ornithine L-aspartate in acute liver failure: A double-blind, randomized, placebo-controlled study. Gastroenterology 136(7):2159-2168
102. Monfort P, Cauli O, Montoliu C, Rodrigo R, Llansola M, Piedrafita B, El Mlili N, Boix J, Agustí A, Felipo V (2009) Mechanisms of cognitive alterations in hyperammonemia and hepatic encephalopathy: Therapeutical implications. Neurochem Int 55(1-3):106-112
103. Moini M, Mistry P, Schilsky ML (2010) Liver transplantation for inherited metabolic disorders of the liver. Curr Opin Organ Transplant 15(3):269-276
104. 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
105. Leonard JV, McKiernan PJ (2004) The role of liver transplantation in urea cycle disorders. Mol Genet Metab 81:S74-S78 (Pubitemid 38402239)
106. Lee B, Goss J (2001) Long-term correction of urea cycle disorders. J Pediatr 138(Suppl):S62-S71 (Pubitemid 32099505)
107. Meyburg J, Das AM, Hoerster F, Lindner M, Kriegbaum H, Engelmann G, Schmidt J, Ott M, Pettenazzo A, Luecke T, Bertram H, Hoffmann GF, Burlina A (2009) One liver for four children: First clinical series of liver cell transplantation for severe neonatal urea cycle defects. Transplantation 87:636-641
108. Krivitzky L, Babikian T, Lee HS, Thomas NH, Burk-Paull KL, Batshaw ML (2009) Intellectual, adaptive, and behavioral functioning in children with urea cycle Disorders. Pediatr Res 66:96-101
109. Enns GM (2010) Nitrogen sparring therapy revisited 2009. Mol Genet Metab 100(Suppl):S65-S71