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Centro de Investigaciones Regionales Dr. Hideyo Noguchi, Universidad Autónoma de Yucatán

2005, Number 3

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Rev Biomed 2005; 16 (3)

An approach to hereditary disorders of urea cycle in the man.

Martín-Hernández I

Language: Spanish
References: 116
Page: 193-206
PDF size: 175.63 Kb.


ABSTRACT

Objectives. This work offers a theoretical and updated review on hereditary disorders of the urea cycle, directed not only to medical professionals in this topic, but also to other specialists interested in the study of inborn errors of metabolism.
Sources of information. Updated articles and books related to the theme. Internet search.
Results. The urea cycle is a fundamental mechanism in mammals in which nitrogen that is not used can be excreted. It involves five enzymes: Carbamylphosphate synthetase, Ornithine transcarbamilase, Arginosuccinate synthetase, Arginosuccinate liase, and Arginase. N-acetyl glutamate synthetase is another enzyme which is essential for the proper operation of the cycle. Malfunction of any of these enzymes results in hyperammonemia. Clinical expression includes anorexia, irritability, lethargy, vomiting, somnolence, desorientation, cerebral edema, coma, and death. The clinical manifestations may appear in the neonatal period and can be fatal, or they may appear any time thereafter with varying degrees of severity. Fundamentally, the diagnosis of these disorders consists of the measurement of different metabolites in blood and urine, and the analysis of enzyme activity. The treatment requires nutritional restriction of proteins, administration of specific amino acids and activation of other pathways of waste nitrogen synthesis and excretion.
Conclusions. Professionals in health facilities and other physicians have relatively little experience in dealing with these disorders, because these disorders are rare. Hence, early suspicion of the diagnosis of a urea cycle disorder, and prompt referral to specialized center is vital.


REFERENCES

  1. 1.- Voet Cohen PP. The ornitine-urea cycle: biosynthesis and regulation of carbamyl phosphate synthetase I and ornitine transcarbamilase. Curr Top Cell Regul 1981; 18: 1-19.

  3. 2.- Voet D, Voet JG. Bioquímica. 1a. ed. Barcelona: Ediciones Omega; 1992. p. 725-78.

  5. 3.- Tong BC, Balbul A. Cellular and physiological effects of arginine. Mini Rev Med Chem 2004; 4: 823-32.

  7. 4.- Cornejo V, Raimann E. Errores innatos del metabolismo de los aminoácidos. En: Colombo M, Cornejo V, Raimann E, editores. Errores innatos del metabolismo del niño. 2ª ed. Santiago de Chile: Editorial universitaria SA; 2003. p. 71-138.

  9. 5.- Zschocke J, Hoffmann G. Metabolic pathways and their disorders. En: Zschocke J, Hoffmann G, editores. Vademecum metabolicum. Manual of metabolic Pedriatrics.2ª ed. Stuttgart: Milupa GmbH & Co. KG; 1999. p. 35-56.

  11. 6.- Brusilow S, Horwich A. Urea cycle enzymes. En: Scriver Ch, Beaudet A, Sly W, Valle D, editores. The metabolic and molecular bases of inherited disease. 8th ed. New York: McGraw-Hill Inc; 2001.vol. 2: 1909-64.

  13. 7.- Rainmann E, Cornejo V, Mellibosky D, López ME, Godoy X, Colombo M. Citrulinemia. Rev Chil Pediatr 1994; 65: 215-8.

  15. 8.- Meijer AJ, Lamers WH, Chamuleau R. Nitrogen metabolism and ornitine cycle function. Physiol Rev 1990; 70: 701-48.

  17. 9.- Morris SM. Regulation of enzymes of urea and arginine síntesis. Annu Rev Nutr 1992; 12: 81-101.

  19. 10.- Caldovic L, Morizono H, Panglao MG, Gallegos R, Yu X, Shi D, et al. Cloning and expression of the human N-acetylglutamate synthase gene. Biochem Biophys Res Commun 2002; 209: 581-6.

  21. 11.- Summar ML, Hall LD, Eeds AM, Hutcheson HB, Kuo AN, Willis AS, et al. Characterization of the structure and polimorphisms in the human carbamyl phosphate synthetase I gene. Gene 2003; 311: 51-7.

  23. 12.- Sheehy L, Lynch MG. Mutations and polymorphisms in the human ornithine transcarbamylase gene. 2002; 19: 93-107.

  25. 13.- Haberle J, Pauili S, Linneebank M, Kleijer WJ, Bakker HD, Wanders RJ, et al. Structure of the human argininosuccinate synthetase gene and the improved system for molecular diagnostics in patients with classical and mild citullinemia. Hum Genet 2002; 110: 327-33.

  27. 14.- Kobayashi K, Kakinoki H, Fukushige T, Shaheen N, Terazono H, Saheki T. Nature and frecuency of mutations in the argininosuccinate synthetase gene that cause classical citullinemia. Hum Genet 1995; 96: 454-63.

  29. 15.- Online Mendelian Inheritance in Man: N-acetyl glutamate synthetase, 608300. Available from: URL: http//www.ncbi.nlm.nih.gov/OMIM.

  31. 16.- Online Mendelian Inheritance in Man: Carbamoyl phosphate synthetase, 608307. Available from: URL: http//www.ncbi.nlm.nih.gov/OMIM.

  33. 17.- Online Mendelian Inheritance in Man: Ornithine transcarbamilase, 300461. Available from: URL: http//www.ncbi.nlm.nih.gov/OMIM.

  35. 18.- Online Mendelian Inheritance in Man: Arginosuccinate synthetase, 603470. Available from: URL: http//www.ncbi.nlm.nih.gov/OMIM.

  37. 19.- Online Mendelian Inheritance in Man: Arginosuccinate lyase, 608310. Available from: URL: http//www.ncbi.nlm.nih.gov/OMIM.

  39. 20.- Online Mendelian Inheritance in Man: Arginase, 608313. Available from: URL: http//www.ncbi.nlm.nih.gov/OMIM.

  41. 21.- Pintos G, Briones MP, Marchante C, Sanjurjo P,. Protocolo para el diagnóstico, tratamiento y seguimiento de los trastornos del ciclo de la urea. An Esp Pediatr 1997; 89: 1-8.

  43. 22.- Leonard JV. Urea cycle disorders. En:Fernández J, Saudubray JM, Van der Berge G, editores. Inborn metabolic diseases. Berlín: Springer-Verlag; 1995. p. 167-176.

  45. 23.- Wilcox WR, Cederbaum SD. Amino acid metabolism. En: Rimoin E, Connor JM, Pyeritz BR, editores.Emery and Rimoin`s. Principles and practice of medical genetics. 4a ed. New york: Churchill Livingtone; 2002. Vol 2: 2405-40.

  47. 24.- Walker V. Hipoglycaemia and hyperamonaemia. En: Clinical biochemistry and the sick child. Clayton BE, Round JM, editores. Oxford: Blackwell Scientific Publications; 1994. p. 87-120.

  49. 25.- Mathias RS, Kostiner D, Packman S. Hyperammonemia in urea cycle disorders: Role of the nephrologist. Am J Kidney Dis 2001; 37: 1069-80.

  51. 26.- Batshaw ML. Inborn errors of urea synthesis. Ann Neurol 1994; 35: 133-41.

  53. 27.- Batshaw ML: Hyperammonemia. Curr Probl Pediatr 1984; 14: 1-69.

  55. 28.- Ratnakumari L, Qureshi IA, Butterworth RF. Regional aminoacid neurotransmitter changes in brains of spf/Y mice with congenital ornithine transcarbamilase deficiency. Metab Brain Dis 1994; 9: 43-52.

  57. 29.- Blei A, Olafsson Therrien G, Butterworth RF. Ammonia induced brain edema and intracranial hypertension in rats after portocaval anastomosis. Hepatology 1994; 19: 1437-44.

  59. 30.- Butterworth R. Effects of hyperammnonemia on brain function. J Inhit Metab Dis 1998; 21: 6-20.

  61. 31.- Uchino T, Endo F, Matsuda I. Neurodevelopmental outcome of long-term therapy of urea cycle disorders in Japan. J Inherited Metab Dis 1998; 21(suppl 1); 151-9.

  63. 32.- Nicolaides P, Liebsh D, Leonard J, Surtees R. Neurological outcome of patients with ornithine carbamoyltransferase deficiency. Arch Dis Child 2002, 86:54-6.

  65. 33.- Hudak ML, Jones MD, Brusilow. Differentiation of transient hyperammonemia of the newborn and urea cycle enzyme defects by clinical presentation. J Pedriatr 1985; 107: 712-9.

  67. 34.- Nicolaides P, Liebsch D, Dale N, Leonard J, Surtees R. Neurological outcome of patients with ornithine carbamoyltransferase deficiency. Clin Chem 1999; 45: 995-1001.

  69. 35.- Widhalm K, Koch S, Scheibenreiter S. Long-term follow-up of 12 patients with the late-onset variant of argininosuccinic acid lyase deficiency: no impairment of intellectual and psychomotor development during therapy. Pediatrics 1992; 89 (6 Pt 2): 1182-4.

  71. 36.- Cowley DM, Bowling FG, McGill JJ, van Dongen J. Adult-onset arginase deficiency. J Inherit Metab Dis 1998; 21: 677-8.

  73. 37.- Iyer R, Jenkinson CP, Vockley JG, Kern RM. The human arginases and arginase deficiency. J Inherit Metab Dis 1998; 21(Suppl 1): 86-100.

  75. 38.- Picker JD, Puga AC, Levy HL. Arginase deficiency with lethal neonatal expression: evidence for the glutamine hypothesis of cerebral edema. J Pediatr 2003; 142: 349-52.

  77. 39.- Scheuerle AE, McVie R, Beaudet AL, Shapira SK. Arginase deficiency presenting as cerebral palsy. Pediatrics 1993; 91: 995-6.

  79. 40.- Batshaw ML, Thomas GH, Brusilow SW. New approaches to the diagnosis and treatment of inborn errors of urea synthesis. Pediatrics 1981; 68:290-7.

  81. 41.- Steiner RD, Cederbaum SD. Laboratory evaluation of urea cycle disorders. J Pediatr 2001; 138 (1 Pt 2): 21-29. 96.-

  83. 42.- Summar M. Current strategies for the management of neonatal urea cycle disorders. J Pedriat 2001; 130: 30-39.

  84. 43.- Webster DR, Simmons HA, Barry DMJ, Becroft DMO. Pyrimidine and purine metabolites in ornithine carbamoyl transferase deficiency. J Inherited Metab Dis 1981; 4 :27-31.

  86. 44.- Arranz JA, Riudor E, Rodés M, Roig M, Climent C, Rubio V, et al. Optimization of allopurinol challenge: sample purification, protein intake control, and the use of oritidine response as a discriminative variable improve performance of the test for diagnosing orotidine carbamoyltransferase deficiency. Pediatrics 2003; 111: 1123-4.

  88. 45.- Scaglia F, Zheng Q, O´Brien WE, Henry J, Rosenberger J, Reeds P, et al. An integrated approach to the diagnosis and prospective management of partial ornithine transcarbamylase deficiency. Pedriatrics 2002; 109: 150-2.

  90. 46.- Nagata N, Endo F, Matsuda I. Ornithine carbamoyltransferase (OTC) in jejunal mucosa, as a reference of the liver OTC. Clin Chim Acta 1983; 134: 155-66.

  92. 47.- Marescau B, Qureshi IA, De Deyn P, Letarte J, Ryba R, Lowenthal A. Guanidino compounds in plasma, urine and cerebrospinal fluid of hyperargininemic patients during therapy. Clin Chim Acta 1985; 146: 21-7.

  94. 48.- Marescau B, Lowenthal A. Isolation and identification of some guanidino compounds in the urine of patients with hyperargininaemia by liquid chromatography, thin-layer chromatography and gas chromatography spectrometry. J Chromatogr 1981; 224: 185-8.

  96. 49.- Naylor EW, Cederbaum SD. Urinary pyrimidine excretion in arginase deficiency. J Inherit Dis 1981; 4: 207-10.

  98. 50.- Finckh U, Kohlschutter A, Schafer H, Sperhake. Prenatal diagnosis of carbamoyl phosphate synthetase I deficiency by identification of a missense mutation in CPS1. Hum Mutat 1998; 12: 206-11.

  100. 51.- Fox J, Hack AM, Fenton WA, Golbus MS, et al: Prenatal diagnosis of ornithine transcarbamylase deficiency with use of DNA polymorphisms. N Engl J Med 1986; 315: 1205-8.

  102. 52.- Hayakawa M, Kato Y, Takahashi R, Tauchi N. Case of citrullinemia diagnosed by DNA analysis: including prenatal genetic diagnosis from amniocytes of next pregnancy. Pediatr Int 2003; 45: 196-8.

  104. 53.- Haberle J, Koch HG. Genetic approach to prenatal diagnosis in urea cycle defects. Prenat Diagn 2004; 24: 378-83.

  106. 54.- Wilcken B. Problems in the management of urea cycle disorders. Mol Genet Metab 2004; 81 (Suppl 1): 86-91.

  108. 55.- Leonard J. The nutricional management of urea cycle disorders. J Pediatr 2001; 138, 40-45.

  110. 56.- Berry GT, Steiner RD: Long-term management of patients with urea cycle disorders. J Pediatr 2001; 138(1 Pt 2): 56-62.

  112. 57.- McBride KL, Miller G, Carter S, Karpen S, Goss J, Lee B. Developmental Outcomes With Early Orthotopic Liver Transplantation for Infants With Neonatal-Onset Urea Cycle Defects and a Female Patient With Late-Onset Ornithine Transcarbamylase Deficiency. Pediatrics 2004; 114: 523-6.

  114. 58.- Lee B, Goss J. Long-term correction of urea cycle disorders. J Pediatr. 2001; 138:62 -71.

  116. 59.- Horslen SP, McCowan TC, Goertzen TC, Warkentin PI, Bo Cai H, Strom SC, et al. Isolated hepatocyte transplantation in an infant with a severe urea cycle disorder. Pediatrics 2003; 111: 1262-7.




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