Animal Models of Hereditary Hyperammonemias

  • Ijaz A. Qureshi
Part of the Neuromethods book series (NM, volume 22)


Hereditary hyperammonemias can be defined as a group of inborn errors in which the altered gene product would adversely effect the nitrogen metabolism of the affected individuals, causing an abnormal accumulation of ammonia in the blood. These altered gene products primarily include the enzymes and transport proteins that are part of the Krebs-Hensleit ornithine-urea cycle (Fig. l), the principal metabolic pathway for the disposal of ammonia in the mammalian organism. In addition, inherited deficiencies of certain other enzymes and proteins that modify the availability of specific cellular metabolites, thus causing an inhibition of the urea cycle enzymes to induce secondary hyperammonemias, are also included in this group of diseases. Recently, other mutations that hinder the availability of energy-producing substrates necessary for ammonia detoxification at the mitochondrial level have also been included among the list of secondary hyperammonias.
Fig. 1.

The “ornithine-urea” cycle and its metabolic interrelationships with the Krebs′ citric acid cycle and the pathways of glutamine and pyrimidine biosynthesis. The sources of deaminated and transaminated nitrogen incorporated into urea are shown by black dot superscripts. Enzymes No. 1 and 2 of the urea cycle are mitochondrial, whereas enzymes 3–5 are located in the cytosol. Primary urea cycle disorders caused by mutations related to each of these enzymes are known in various human patients.


Urea Cycle Organic Aciduria Urea Cycle Disorder Propionic Acidemia Carbamyl Phosphate 
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  1. Amendt B. A., Greene C., Sweetman L., Cloherty J., Shih V., Moon A., Teel L., and Rhead W. J. (1987) Short-chain acyl-Coenzyme A dehydroge-nase deficiency.J. Clin. Invest. 79, 1303–1309.PubMedCrossRefGoogle Scholar
  2. Anegawa N.J., Robinson, M. B., Qureshi I. A., Coyle J. T., and Batshaw M. L. (1989) Brain serotonin-2 but not serotonin-1A receptors are decreased in the congenitally hyperammonemic, ornithine transcarbamylase deficient, sparse-fur mouse. Pediatr. Res. 24, 194A.Google Scholar
  3. Bachmann C. and Colombo J. P. (1984) Increase of tryptophan and 5-hydroxyindoleacetic acid in the brain of ornithine carbamoyl transferase deficient sparse-fur mice. Pediatr. Res. 18, 372–375.PubMedCrossRefGoogle Scholar
  4. Bachmann C., Brandis M., Weissenbarth-Redel E., Burghard R., and Colombo J. P. (1988) N-acetylglutamate synthetase deficiency, a second patient. J. Inherited Metab. Dis. 11, 191–193.PubMedCrossRefGoogle Scholar
  5. Bahl J. J. and Bressler R. (1987) The pharmacology of carnitine. Ann. Rev. Pharmacol. Toxicol. 27, 257–277.CrossRefGoogle Scholar
  6. Barshop B. A., Breuer J., Holm J., Lesle J., and Nyhan W. L. (1989) Excretion of hippuric acid during sodium benzoate therapy in patients with hyperglycinemia or hyperammonemia. J. Inherited Metab. Dis. 12, 72–79.PubMedCrossRefGoogle Scholar
  7. Batshaw M. L. (1984) Hyperammonemia. Curr. Probl. Pediatr. 14, 1–67.PubMedCrossRefGoogle Scholar
  8. Batshaw M. L., Hyman S. L., Mellit D., Thomas G. H., Demauro R., and Coyle J. T. (1986) Behavioral and neurotransmitter changes in the urease infused rat. A model of congenital hyperammonemia. Pediatr. Res. 20, 1310–1315.PubMedCrossRefGoogle Scholar
  9. Batshaw M. L., Hyman S. L., Bachmann C., Qureshi I. A., and Coyle J. T. (1987) Animal models of congenital hyperammonemia, in Animal Models of Dementia (Coyle J. T., ed.), Alan R. Liss Inc., New York, pp.163–198.Google Scholar
  10. Batshaw M. L., Hyman S. L., Coyle J. T., Robinson M. B., Qureshi I. A., Mellits E. D., and Quaskey S. (1988) Effect of sodium beruoate and sodium phenylacetate on brain serotonin turnover in the ornithine transcarbamylase-deficient sparse-fur mouse. Pediatr. Res. 23, 368–374.PubMedCrossRefGoogle Scholar
  11. Beaudet A. L., Striver C. R., Sly W. S., and Valle D. (1989) Genetics and biochemistry of variant human phenotypes, in, The Metabolic Basis of inherited Disease. McGraw-Hill, New York, pp.3–163.Google Scholar
  12. Bieber L. L. (1988) Carnitine. Ann. Rev. Biochem. 57, 261–283.PubMedCrossRefGoogle Scholar
  13. Botschner J., Smith D. W., Simell O., and Scriver G. R. (1989) Comparison of ornithine metabolism in hyperornithinemia-hyperammonemia-homocitrullinuria syndrome, lysinuric protein intolerance and gyrate atrophy fibroblasts. J Inherited Metab. Dis. 12, 33–40.PubMedCrossRefGoogle Scholar
  14. Briand P., François B., Rabier D., Cathelineau L. (1982) Ornithine transcarbamylase deficiencies in human males: kinetic and immuno-chemical classification. Biochim. Biophys. Acta 704, 100–106.PubMedCrossRefGoogle Scholar
  15. Briand P., Cathelineau L., Kamoun P., Gigot D., Penninckx M. (1981) Increase of ornithine transcarbamylase protein in sparse-fur mice with ornithine transcarbamylase deficiency. FEBS Lett. 130, 65–68.PubMedCrossRefGoogle Scholar
  16. Brown G. K., Scholem R. D., Hunt S. M., Harrison J. R., and Pollard A. C. (1987) Hyperammonemia and lactic acidosis in a patient with pyruvate dehydrogenase deficiency. J. Inherited Metab. Dis. 10, 359–366.PubMedCrossRefGoogle Scholar
  17. Brownstein D. G., Johnson E. A., and Smith A. A. (1984) Spontaneous Reyes-like syndrome in BALB/cByJ mice. Lab. Invest. 51, 386–395.PubMedGoogle Scholar
  18. Brusilow G. K. and Horwich A. L. (1989) Urea cycle enzymes, in The Metabolic Basis of Inherited Disease, McGraw-Hill, New York, pp. 629–663.Google Scholar
  19. Carroll J. E., Carter A. L., and Perlman S (1987) Carnitine deficiency revisited. J. Nutr. 117, 1501–1503.PubMedGoogle Scholar
  20. Carter A. L., Eller A. G., Rufo S., Metoki K., and Hommes F. A. (1984) Further evidence for a separate enzymic entity for the synthesis of homocitrulline distinct from the regular ornithine transcarbamylase. Enzyme 32, 26–34.PubMedGoogle Scholar
  21. Cavard C., Grimber G., Dubois N., Chasse J. F., Bennoun M., Minet-Thuriaux M., Kamoun P., and Briand P. (1988) Correction of mouse ornithine transcarbamylase deficiency by gene transfer into the germ line. Nucleic Acid Res. 16, 2099–2110.PubMedCrossRefGoogle Scholar
  22. Cerny M. E. (1987) Animal model provides understanding of urea-cycle defects. Res. Resources Rep. 11, 7–9.Google Scholar
  23. Chalmers R. A. (1989) Current research in the organic acidurias. J. Inherited Metab. Dis. 12, 225–239.PubMedCrossRefGoogle Scholar
  24. Chaouloff F., Laude D., Mignot E., Kamoun P., and Elghozi J. L. (1985) Tryptophan and serotonin turnover rate in the brain of genetically hyperammonemic mice. Neurochem. Int. 7, 143–153.PubMedCrossRefGoogle Scholar
  25. Coude F. X. and Grimber G. (1984) Inhibition of urea synthesis by pent-4-enoic acid: potentiation by ammonia. Biochem. Biophys. Res. Commun. 118, 47–52PubMedCrossRefGoogle Scholar
  26. De Deyn P. P., MacDonald L. R., Marescau B., and Lowenthal A. (1989) Alpha-keto-delta-guanidinovaleric acid, a compound isolated from hyperargininemic patients, displays epileptogenic activities, in Guanidines-2 (Mori A. and Cohen B., eds.), Plenum Press, New York pp. 251–260.Google Scholar
  27. Demars R., Levan S. L., Trend B. L., and Russel L. B. (1976) Abnormal ornithine carbamyl transferase in mice having the sparse-fur mutation. Proc. Natl. Acad. Sci. USA 23, 1693–1698.CrossRefGoogle Scholar
  28. Demetriou A. A., Whiting J. F., Feldman D., Levenson S. M., Chowdhury N. R., Moscioni A. D., Kram M., and Chowdhury J. R. (1986) Replacement of liver function in rats by transplantation of microcarrier attached hepatocytes. Science 233, 1190,1191.CrossRefGoogle Scholar
  29. Derr R. F. and Zieve L. (1976) Effect of fatty acids on the disposition of ammonia. J. Pharmacol. Exp. Ther. 197, 675–680.PubMedGoogle Scholar
  30. Deshmukh D. R., Singh K. R., Meert K., and Deshmukh G. D. (1990) Failure of L-carnitine to protect mice against hyperammonemia induced by ammonium acetate or urease injection. Pediatr. Res. 28, 256–260.PubMedCrossRefGoogle Scholar
  31. Doolittle, D. P., Hulbert L. L., and Cordy C. (1974) A new allele of the sparse-fur gene in the mouse. J. Hered. 65, 194,195.Google Scholar
  32. Eriksson B. O., Gustafson B., Lindstedt S., and Nordin I. (1989) Transport of carnitine into cells in hereditary carnitine deficiency. J. Inherited Metab. Dis. 12, 108–111.PubMedCrossRefGoogle Scholar
  33. Gordon B. A., Gatfield D. P., and Haust D. M. (1987) The hyperornithinemia, hyperammonemia, homocitrullinuria syndrome: an ornithine transport defect remediable wth ornithine supplements. Clin. Invest. Med. 10, 329–336.PubMedGoogle Scholar
  34. Gregersen N., Kolvraa S., and Mortensen P. B. (1986) Acyl-CoA:glycine N-acyltransferase: in vitro studies on the glycine conjugation of straight-and branched-chained acyl-CoA esters in human liver. Biochem. Med. Metab. Biol. 35, 210–218.PubMedCrossRefGoogle Scholar
  35. Grompe M., Jones S. N., Munir I., and Caskey C. T. (1989) Germ-line correction of the ornithine transcarbamylase deficient sparse-fur (spf) mouse. Pediatr. Res. 24, 141A.Google Scholar
  36. Gushiken T., Yoshimura N., and Takezori S. (1985) Transient hyper-ammonemia during aging in ornithine transcarbamylase deficient sparse-fur mice. Biochem. Int. 11, 637–643.PubMedGoogle Scholar
  37. Hagiwara H., Nagasaki T., Saito Y., and Inada Y. (1982) Fibrin membrane endowed with biological function. VII. An approach to an artificial liver: conversion of ammonia to urea in vitro. Biochem. Biophys. Res. Commun. 104, 507–511.PubMedCrossRefGoogle Scholar
  38. Hale D. E. and Thorpe C. (1989) Short-chain 3-OH acyl-CoA-dehydrogenase deficiency. Pediatr. Res. 25, 397A (abstract).Google Scholar
  39. Harper P. A. W., Healey P. J., and Deumis, J. A. (1989) Animal model of human disease. Citrullmemia (argininosuccinate synthetase deficiency). Am. J. Pathol. 135, 1213–1215.PubMedGoogle Scholar
  40. Hindfelt B. and Sieso B. K. (1971) Cerebral effect of acute ammonia intoxication. II. The effect of energy metabolism. Scand. J. Clin. Lab. Invest. 28, 365–374.PubMedCrossRefGoogle Scholar
  41. Howell J., Wareham K. A., and Williams E. D. (1985) Clonal origin of mouse liver cell tumors. Am. J. Pathol. 121, 426–432.PubMedGoogle Scholar
  42. Hyland K., Smith I., Clayton P. T., and Leonard J. V. (1986) Impaired neuro-transmitter amine metabolism in arginase deficiency. J. Neurol. Neurosurg. Psychiatr. 49, 1188–1189.Google Scholar
  43. Hyman S. L., Coyle J. T., Parke J. C., Porter G., Thomas G. H., Jankel W., and Batshaw M. L. (1986) Anorexia and altered serotonin metabolism in a patient with argininosuccinic aciduria J. Pediatr. 108, 705–709.PubMedCrossRefGoogle Scholar
  44. Hyman S. L., Porter C. A., Page, T. J., Iwata B. A., Kissel R., and Batshaw M. L. (1987) Behaviour management of feeding disturbances in urea cycle and organic acid disorders. J. Pediatr. 111, 558–562.PubMedCrossRefGoogle Scholar
  45. Imamura Y., Saheki T., Noda T., Arakawa M., Koizumi T., and Hayakawa J. (1990) Abnormal gene expression of its urea cycle enzymes in C3H-H-2-mice with juvenile steatosis. Proceedings of the V Int. Congress of Inborn Errors, Asilomar, pp. 39.Google Scholar
  46. Jackson M. J., Beaudet A. L., and O’Brien W. E. (1986) Mammallian urea cycle enzymes. Ann. Rev. Genet. 20, 431–464.PubMedCrossRefGoogle Scholar
  47. Kobori J. A., Johnston K., Sweetman L., Schmidt K., Jurecki E., Wolf B., Goodman S., and Packman S. (1989) Isolated 3-methylcrotonyl CoA carboxylase deficiency presenting as a Reyes-like syndrome. Pediatr. Res. 25, 142A.Google Scholar
  48. Kolvraa S. and Gregersen N. (1986) Acyl-CoA:glycine N-acyltransferase: organelle localization and affinity toward straight-and branched-chained acyl-CoA esters in rat liver. Biochem. Med. Metab. Biol. 36, 98–105PubMedCrossRefGoogle Scholar
  49. Kurczynski T. W., Hoppel C. L., Goldblatt P. J., and Gunning W. T. (1989) Metabolic studies of carnitine in a child with propionic acidemia. Pediatr. Res. 26, 63–66.PubMedCrossRefGoogle Scholar
  50. Kuwajima M., Norio K., Horiuchi M., Imamura Y., Ono A., Inui Y., and Saleki T. (1991) Animal model of systemic carnitine deficiency. Biochem. Biophys. Res. Commun. 174, 1090–1094.PubMedCrossRefGoogle Scholar
  51. Largilliaire, C., Houssin D., Gottrand F., Mathey C., Checoury A., Alagille, D., and Farriaux J. P. (1989) Liver transplantation for ornithine transcarbamylase in a girl. J. Pediatr. 115, 415–417.CrossRefGoogle Scholar
  52. Letarte J., Qureshi I. A., Goddard M., and Ouellet R. (1985) Chrome benzoate therapy in a male child with a partial deficiency of ornithine transcarbamylase. J. Pediatr. 106, 794–797.PubMedCrossRefGoogle Scholar
  53. Levine R. L., Hoogenraas N. L., and Kretobruer N. (1974) A review: biological and clinical aspects of pyrimidine metabolism. Pediatr. Res. 8, 824–832.Google Scholar
  54. Lowenthal A. and Marescau B. (1989) Hyperargininemia. in Guanidines-2 (Mori A. and Cohen B., eds.), Plenum Press, New York. pp. 225–232.Google Scholar
  55. Maddaiah V. T. (1985) Ammonium inhibition of fatty acid oxidation in rat liver mitochondria: a possible cause of fatty liver in Reye’s syndrome and urea cycle defects. Biochem. Biophys. Res. Commun. 127(2), 565–570.PubMedCrossRefGoogle Scholar
  56. Maddaiah V. A. and Miller P. S. (1989) Effects of ammonium chloride, salcylate and carnitine on palmitic acid oxidation in rat liver slices. Pediatr. Res. 25(2), 119–123.PubMedCrossRefGoogle Scholar
  57. Malo C., Qureshi I. A., and Letarte J. (1986) Postnatal maturation of enterocytes in sparse-fur mutant mice. Am. J. Physiol. 250, G177–G184.PubMedGoogle Scholar
  58. Marklova E., Verner P., Pehal F., Bratova M., and Polak J. (1987) A new case of 3-hydroxy3-methylglutaryl-coenzyme A lyase deficiency. J. Inherited Metab Dis 10, 399.PubMedCrossRefGoogle Scholar
  59. Matsuo M., Saiki K., Tanabe J., Nakamura H., and Matsuo T. (1987) Citrullinemia: an infantile form with p-hydroxyphenylpyruvic and p-hydroxyphenyllactic acidurias. J Inherited Metab. Dis. 10, 276.PubMedCrossRefGoogle Scholar
  60. McCormick K., Viscardi R. M., Robinson B., and Heininger J. (1985) Partial pyruvate decarboxylase deficiency with profound lactic acidosis and hyperammonemia: responses to dichloroacetate and benzoate. Am. J. Med. Genet. 22, 291–299.PubMedCrossRefGoogle Scholar
  61. Mendenhall C. L., Rouster S., Marshall L., and Wesner R. (1986) A new therapy for portal-systemic encephalopathy. Am. J. Gastroenterol. 81, 540–543PubMedGoogle Scholar
  62. Michalak A. and Qureshi I. A. (1990) Plasma and urinary levels of carnitine in different experimental models of hyperammonemia and the effect of sodium benzoate treatment. Biochem. Med. Metab. Biol. 43, 163–174.PubMedCrossRefGoogle Scholar
  63. O’Connor J. E., Renau-Piqueras J., and Grisolia S. (1984) Effects of urease-induced hyperammonemia in mouse liver: ultrastructural, stereologic and biochemical study. Virchows Arch. (Cell Pathol.) 46, 187–197.CrossRefGoogle Scholar
  64. Ohtake A., Takayanagi M., Yamamoto S., Hakinuma H., Nakaima H., Tatibana M., and Mori M. (1986) Molecular basis of ornithine transcarbamylase deficiency in spf and spf ash mutant mice. J. Inherited Metab. Dis. 9, 289–291.PubMedCrossRefGoogle Scholar
  65. Pollitt R. J. (1989) Disorders of mitochondrial beta-oxidation: prenatal and early postnatal diagnosis and their relevance to Reye’s syndrome and sudden infant death. J. Inherited Metab. Dis. 12(Suppl. 1), 215–230.PubMedCrossRefGoogle Scholar
  66. Qureshi I. A., Letarte J., and Ouellet R. (1979) Ornithine transcarbamylase deficiency in mutant mice. I. Studies on the characterization of enzyme defect and suitability as animal model of human disease. Pediatr. Res. 13, 807–811.PubMedCrossRefGoogle Scholar
  67. Qureshi I. A. and Letarte J. (1982) Spontaneous animal models of ornithine transcarbamylase deficiency: studies on serum and urinary nitrogenous metabolites, in Urea Cycle Diseases, Plenum Press New York, pp. 173–183.Google Scholar
  68. Qureshi I. A., Letarte J., and Ouellet R. (1982a) Congenital hyperammonemia, model no. 235, in Handbook: Animal Models of Human Disease, Armed Forces Institute of Pathology, Washington, D.C., pp. 1–2.Google Scholar
  69. Qureshi I. A., Letarte J., and Ouellet R. (1982b) Activity of orotate metabolizing enzyme complex and various urea cycle enzymes in mutant mice with ornithine transcarbamylase deficiency. Experientia 38, 308,309.CrossRefGoogle Scholar
  70. Qureshi I. A., Letarte J., and Ouellet R. (1985a). Expression of ornithine transcarbamylase deficiency in the small intestine and colon of sparse-fur mutant mice. J. Pediatr. Gastroenterol. Nutr. 4, 118–124.PubMedCrossRefGoogle Scholar
  71. Qureshi I. A., Letarte J., Tuchweber, B., Yousef I., and Qureshi S. R. (1985b) Hepatotoxicity of sodium valproate in ornithine transcarbamylase deficient mice. Toxicol. Lett. 25, 297–306.PubMedCrossRefGoogle Scholar
  72. Qureshi I. A., Rouleau J., Letarte J., and Ouellet R. (1986a) Significance of transported glycine in the conjugation of sodium benzoate in spf mutant mice with ornithine transcarbamylase deficiency. Biochem. Int. 12, 839–846.PubMedGoogle Scholar
  73. Qureshi I. A., Letarte J., Lebel S., and Ouellet R. (1986b) The variability of enzyme activity and orotate excretion in spf/+ heterozygote mice with ornithine transcarbamylase deficiency. Diabete Metab. (Paris) l2, 250–255.Google Scholar
  74. Qureshi I. A., Marescau B., Levy M., De Deyn P., Letarte J., and Lowenthal, A. (1989a) Serum and urinary guanidine compounds in “sparse-fur” mutant mice with ornthine transcarbamylase deficiency, in Guanidines-2 (Mori A. and Cohen B., eds.), Plenum Press, New York, pp.45–52.Google Scholar
  75. Qureshi I. A., Lebel J., and Letarte J. (1989b) Development and inducibility of the hepatic and renal hippurate-synthesizing system in spf mutant mice. Biochem Int. 19, 657–666.PubMedGoogle Scholar
  76. Qureshi I. A. and Michalak A. (1992) Therapeutic uses of sodium benzoate and its potential for toxicity—a review. (submitted).Google Scholar
  77. Rhead W. J., Wolff J. A., Lipson M., Falace P., Desal N., Fritchman K., Moon A., and Sweetman L. (1987) Clinical and biochemical variation and family studies in the multiple acyl-CoA dehydrogenation disorders. Pediatr. Res. 21, 371–376.PubMedCrossRefGoogle Scholar
  78. Rinaldo P., O’Shea J. J., Coates P. M., Hale D. E., Stanley C. A., Tanaka K. (1988) Medium-chain acyl-CoA dehydrogenase deficiency: diagnosis by stable-isotope dilution measurement of urinary n-hexanoylglycine and 3-phenylpropionylglycine. N. Engl. J. Med. 319, 1308–1313.PubMedCrossRefGoogle Scholar
  79. Rinaldo P., O’Shea J. J., Goodman S. I., Miller L. V., Fennessey P. V., Whelan D. T., Hill R. E., and Tanaka K. (1989) Comparison of urinary acylglycines and acylcarnitines as diagnostic markers of medium-chain acyl-CoA dehydrogenase deficiency. J. Inherited Metab. Dis. 12(Suppl. 2), 325–328.PubMedGoogle Scholar
  80. Robinson B. H. (1989) Lactic acidemia, in The Metabolic Basis of Inherited Disease, McGraw-Hill, New York, pp.869–888.Google Scholar
  81. Rodes M., Ribes A., Pineda M., Alvarez L., Fabregas I., Fernandez Alvarez E., Coude F. X., and Grimber G. (1987) A new family affected by the syndrome of hyperornithinemia, hyperammonemia and homocitrullinemia. J. Inherited Metab. Dis. 10, 73–81PubMedCrossRefGoogle Scholar
  82. Roe C. R. and Coates P. M. (1989) Acyl-CoA dehydrogenase deficiencies, in The Metabolic Bass of Inherited Disease, McGraw-Hill, New York, pp. 889–914.Google Scholar
  83. Rosenberg L. E. and Fenton W. A. (1989) Disorders of propionate and methylmalonate metabolism, in The Metabolic Basis of Inherited Disease, McGraw-Hill, New York, pp.821–844.Google Scholar
  84. Saudubray J. M., Ogier H., Bonnefont J. P., Munnich A., Lombes A., Herve F., Mitchell G., The B. P., Specola N., Parvy P., Bardet, J., Rabier D., Coude M., Charpentier C., and Frezal J. (1989) Clinical approach to inherited metabolic diseases in the neonatal period: a 20 year survey. J. Inherited Metab. Dis. 12(Suppl. 1), 25–41.PubMedCrossRefGoogle Scholar
  85. Simell O., Sipila I., Rajantie J., Valle D., and Brusilow S. W. (1986) Waste nitrogen excretion via amino acid acylation: benzoate and phenylacetate in lysinuric protein intolerance. Pediatr. Res. 20, 1117–1121.PubMedCrossRefGoogle Scholar
  86. Smith I., Howells D. W., and Hyland K. (1986) Pteridines and monoamines: relevance to neurological damage. Postgrad. Med. J. 62, 113–123.PubMedCrossRefGoogle Scholar
  87. Souba W. W. (1987) Interorgan ammonia metabolism in health and disease. J. Parent. Ent. Nutr. 11, 569–579.CrossRefGoogle Scholar
  88. Spector E. B. and Mozzocchl B. S. (1983) The sparse-fur mouse: an animal model for a human inborn error of metabolism, in Orphan Drugs and Orphan Diseases Alan R. Liss Inc., New York, pp. 85–96.Google Scholar
  89. Stanley C. A. (1987) New genetic defects in mitochondrial fatty acid oxidation and carnitine deficiency. Adv. Pediatr. 34, 59–88.PubMedGoogle Scholar
  90. Stewart P. M. and Walser M. (1980) Failure of the normal ureagenic response to amino acids in organic acid loaded rats. Proposed mechanisms for the hyperammonemia in propionic and methylmalonic aciduria. J. Clin. Invest. 66, 484–492.PubMedCrossRefGoogle Scholar
  91. Strombek D. R. Meyer D. T., and Freedland R. A. (1975) Hyperammonemia due to a urea cycle enzyme deficency in two dogs. J. Am. Vet. M. Assoc. 1966, 1109–1111.Google Scholar
  92. Sweetman L. (1989) Branched chain organic acidurias, in The Metabolic Basis of Inherited Disease, McGraw-Hill, New York, pp.791–819.Google Scholar
  93. Treem W. R., Stanley C. A., Finegold D. N., Hale D. E., and Coates P. M. (1988) Primary carnitine deficiency due to a failure of carnitine transport in kidney, muscle and fibroblasts. N. Engl. J. Med. 319, 1331–1336.PubMedCrossRefGoogle Scholar
  94. Tsuji S., Ogawa K., Takasaka H., Sonoda T., and Mori M. (1982) Clonal origin of 6-glutamyl transpeptidase positive hepatic lesions induced by initiation-promotion in ornithine carbamyltransferase mosaic mice. Jpn J. Cancer. Res. 79, 148–151.Google Scholar
  95. Uribe M., Bosques F., Poo J., Valdovinos F., Melandez N., Delamora G., and Gil S. (1988) A double-blind randomized trial of sodium benzoate versus lactulose in patients with chronic portal systemic encephalopathy. IASL-CASL lnternational Postgraduate Course and Meeting 245 (Abstract).Google Scholar
  96. Valle D. and Simell O. (1989) The hyperornithinemias, in The Metabolic Basis of Inherited Disease, McGraw-Hill, New York pp. 599–627.Google Scholar
  97. Vasudevan S., Lee G., Qureshi I. A., Rao P. M., Rajalakshmi S., and Sarma D. S. R. (1988) Studies of metabolic initiation and tumor promotion, in Chemical Carcinogenesis (Feo F., Parni P., Columbiano A., and Garcea R., eds.), Plenum Press, New York pp.317–322.Google Scholar
  98. Veres G., Gibbs R. A., Scherer S. E., and Caskey C. T. (1987) The molecular basis of the sparse-fur mutation. Science 237, 415–417.PubMedCrossRefGoogle Scholar
  99. Wareham K. A., Howell S., Wilharin D., and Williams E. D. (1983) Studies of X-chromosomal inactivation with an improved histochemical technique for ornithine carbamyl transferase. Histochem. J. 15, 363–371.PubMedCrossRefGoogle Scholar
  100. Williams D. A., Orkin S. H., and Mulligan R. C. (1986) Retrovirus-mediated transer of human adenosine deaminase gene sequences into cells in culture and into murine hematopoietic cells in vivo. Proc. Natl. Acad. Sci. USA 83, 2566–2570.PubMedCrossRefGoogle Scholar
  101. Wood P. A., Amendt B. A., Rhead W. J., Millington D. S., Inoue F., and Armstrong D. (1989) Short-chain acyl-coenzyme: A dehydrogenase deficiency in mice. Pediatr. Res. 25, 38–43.PubMedCrossRefGoogle Scholar
  102. Zieve F. J., Zieve L., Doizaki W. M., and Gilsdorf R. B. (1974) Synergism between ammonia and fatty acids in the production of coma: implications for hepatic coma. J. Pharmacol. Exp Ther. 191, 10–16.PubMedGoogle Scholar

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© The Humana Press Inc 1992

Authors and Affiliations

  • Ijaz A. Qureshi
    • 1
  1. 1.Departments of Pediatrics and NutritionUniversity of MontrealMontrealCanada

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