Skip to main content
SpringerLink
Log in

Ornithine carbamoyl transferase deficiency: Findings, models and problems

  • The X Chromosome
  • Published:
Journal of Inherited Metabolic Disease

Summary

The initial clinical symptoms of ornithine carbamoyl transferase deficiency depend on the age of onset. Respiratory distress on the first day of life does not allow exclusion of OCT deficiency in the individual patient. The acid-base status is not useful as a discriminant between urea-cycle disorders and organic acidurias. Beyond the neonatal age, a second period of increased risk for often lethal hyperammonaemic crises is found between 12 and 15 years of age. For definite diagnosis (pre- and postnatal) of heterozygotes the quantity of tissue obtained should be sufficient to obtain a representative sample for a mosaic structure. Experimental work gives some clues for the interpretation of reversible symptoms of hyperammonaemia. The increased transport of tryptophan at the blood-brain barrier in presence of increased glutamine concentration in tissue appears to depend on intact gammaglutamyl transpeptidase in brain microvessels and involves at least in part the L-carrier. Animal research on the mechanisms leading to irreversible damage in hyperammonaemia should be encouraged in order to define reliable predictive criteria for clinical decisions.

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

Similar content being viewed by others

References

  • Bachmann C (1974) Urea cycle. In Nyhan WL, ed.Heritable Disorders of Aminoacid Metabolism. New York: Wiley, 361–386.

    Google Scholar 

  • Bachmann C (1983) Brain tryptophan uptake and glutamine synthetase in hyperammonemic rats.Hoppe Seyler's Z Physiol Chem 364: 1255–1256.

    Google Scholar 

  • Bachmann C (1987) Diagnosis of urea cycle disorders.Enzyme 38: 233–241.

    Google Scholar 

  • Bachmann C (1990) Urea cycle disorders. In Fernandes J, Saudubray JM, Tada K, eds.Inborn Metabolic Diseases. Berlin: Springer, 211–228.

    Google Scholar 

  • Bachmann C, Colombo JP (1981) Computer simulation of the urea cycle: Trials for an appropriate model.Enzyme 26: 259–264.

    Google Scholar 

  • Bachmann C, Colombo JP (1983) Increased tryptophan uptake into the brain in hyperammonemia.Life Sci 33: 2417–2424.

    Google Scholar 

  • 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.

    Google Scholar 

  • Bachmann C, Colombo JP (1988) Acid-base status and plasma glutamine in patients with hereditary urea cycle disorders. In Soeters PB, Wilson JHP, Meijer AJ, Holm E, eds.Advances in Ammonia Metabolism and Hepatic Encephalopathy. Amsterdam: Elsevier, 72–78.

    Google Scholar 

  • Bachmann C, Lüthi H, Gradwohl M, Colombo JP (1986) Brain uptake of tryptophan in urease injected hyperammonemic rats after treatment with benzoate or hippurate.Biochem Med Metab Biol 36: 214–219.

    Google Scholar 

  • Bachmann C, Schrämmli A, Colombo JP (1988) Tryptophan transport into isolated microvessels of porcine brain. In Soeters PB, Wilson JHP, Meijer AJ, Holm E, eds.Advances in Ammonia Metabolism and Hepatic Encephalopathy. Amsterdam: Elsevier, 469–473.

    Google Scholar 

  • Batshaw ML (1984) Hyperammonemia.Curr Prob Pediatr 14: 1–69.

    Google Scholar 

  • Batshaw ML, Brusilow S, Waber L et al (1982) Treatment of inborn errors of urea synthesis: activation of alternative pathways of waste nitrogen synthesis and excretion.N Engl J Med 306: 1387–1392.

    Google Scholar 

  • Batshaw ML, Hyman SL, Coyle JT et al (1988) Effect of sodium benzoate and sodium phenylacetate on brain serotonin turnover in the ornithine transcarbamylase-deficient sparse-fur mouse.Pediatr Res 23: 368–374.

    Google Scholar 

  • Brusilow SW, Horwich AL (1989) Urea cycle enzymes. In Scriver CR, Beaudet AL, Sly WS, Valle D, eds.The Metabolic Basis of Inherited Disease. New York: McGraw-Hill, 629–663.

    Google Scholar 

  • Brusilow S, Tinker J, Batshaw ML (1980) Amino acid acylation: a mechanism of nitrogen excretion in inborn errors of urea synthesis.Science 207: 659–661.

    Google Scholar 

  • Deshmukh DR, Singh KR, Meert K, Deshmukh GD (1990) Failure ofl-carnitine to protect mice against hyperammonemia induced by ammonium acetate or urease injection.Pediatr Res 28: 256–260.

    Google Scholar 

  • Dhondt JL, Farriaux JP (1991) Inborn errors of the urea cycle and other hyperammonemias. In Schaub J, Van Hoof F, Vis HL, eds.Inborn Errors of Metabolism. New York: Nestec Ltd., Raven Press, Ltd., Vevey, 109–124.

    Google Scholar 

  • 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: 67–70.

    Google Scholar 

  • Eggermont E, Devlieger H, Marchal G et al (1980) Angiographic evidence of low portal liver perfusion in transient neonatal hyperammonemia.Acta Paediatr Belg 33: 163–169.

    Google Scholar 

  • El-Defrawy SR, Boegman RJ, Jhamandas K, Beninger RJ (1986) The neurotoxic actions of quinolinic acid in the central nervous system.Can J Physiol Pharmacol 64: 369–375.

    Google Scholar 

  • Fox JE, Rosenberg LE (1988) Toward a molecular understanding of ornithine transcarbamylase deficiency.Adv Neurol 48: 71–81.

    Google Scholar 

  • Friolet R, Colombo JP, Lazeyras F et al (1989) In vivo 31-P NMR spectroscopy of energy rich phosphates in the brain of hyperammonemic rats.Biochem Biophys Res Commun 159: 815–820.

    Google Scholar 

  • Grompe M, Jones StN, Caskey CT (1990) Molecular detection and correction of ornithine transcarbamylase deficiency.Trends Genet 6: 335–339.

    Google Scholar 

  • Hayasaka K, Metoki K, Ishiguro S et al (1987) Partial ornithine transcarbamylase deficiency in females: diagnosis by an immunohistochemical method.Eur J Pediatr 146: 370–372.

    Google Scholar 

  • Holzgreve W, Golbus MS (1984) Prenatal diagnosis of ornithine transcarbamylase deficiency utilizing fetal liver biopsy.Am J Hum Genet 36: 320–328.

    Google Scholar 

  • Hudak ML, Jones MD Jr, Brusilow SW (1985) Differentiation of transient hyperammonemia of the newborn and urea cycle enzyme defects by clinical presentation.J Pediatr 107: 712–719.

    Google Scholar 

  • Hyman SL, Porter CA, Page TJ, Iwata BA, Kissel R, Batshaw ML (1987) Behavior management of feeding disturbances in urea cycle and organic acid disorders.J Pediatr 111: 558–562.

    Google Scholar 

  • James JH, Jeppsson B, Ziparo V, Fischer JE (1979) Hyperammonemia, plasma aminoacid imbalance, and blood-brain amino acid transport: a unified theory of portal-systemic encephalopathy.Lancet 2: 772–775.

    Google Scholar 

  • Matsuda I, Nagata N, Matsuura T et al (1991) Retrospective survey of urea cycle disorders: Part 1. Clinical and laboratory observations of thirty-two Japanese male patients with ornithine transcarbamylase deficiency.Am J Med Genet 38: 85–89.

    Google Scholar 

  • Moroni F, Lombardi G, Carla V, Pellegrini D, Carassale GL, Cortesini C (1986) Content of quinolinic acid and of other tryptophan metabolites increases in brain regions of rats used as experimental models of hepatic encephalopathy.J Neurochem 46: 869–874.

    Google Scholar 

  • Msall M, Batshaw ML, Suss R, Brusilow SW, Mellits ED (1984) Neurologic outcome in children with inborn errors of urea synthesis. Outcome of urea-cycle enzymopathies.N Engl J Med 310: 1500–1505.

    Google Scholar 

  • O'Connor JE, Costell M, Grisolia S (1987) The potentiation of ammonia toxicity by sodium benzoate is prevented byl-carnitine.Biochem Biophys Res Commun 145: 817–824.

    Google Scholar 

  • Popova NK, Kunosova AV (1985) Brain and peripheral effects of serotonin on thermoregulation.Biogenic Amines 3: 125–134.

    Google Scholar 

  • Post C, Minor BG, Davies M, Archer T (1986) Analgesia induced by 5-hydroxytrptamine receptor agonists is blocked or reversed by noradrenaline-depletion in rats.Brain Res 363: 18–27.

    Google Scholar 

  • Ricciuti FC, Gelehrter TD, Rosenberg LE (1976) X-chromosome inactivation in human liver: confirmation of X-linkage of ornithine transcarbamylase.Am J Hum Genet 28: 332–338.

    Google Scholar 

  • Rodeck CH, Patrick AD, Pembrey ME, Tzannatos C, Whitfield AE (1982) Fetal liver biopsy for prenatal diagnosis of ornithine carbamyl transferase deficiency.Lancet 2, 297–300.

    Google Scholar 

  • Rössle M, Deckert J, Mullen KD et al (1990) [Autoradiography determination of the GABA(A) receptor density in the brain of rats with portacaval shunt]. Autoradiographische Bestimmung der GABA(A)-Rezeptorendichte im Gehirn von Ratten mit portokavalem Shunt.Z Gastroenterol 28: 142–146.

    Google Scholar 

  • Tuchman M, Tsai MY, Holzknecht RA, Brusilow SW (1989) Carbamyl phosphate synthetase and ornithine transcarbamylase activities in enzyme-deficient human liver measured by radiochromatography and correlated with outcome.Pediatr Res 26: 77–82.

    Google Scholar 

  • Wareham KA, Howell S, Williams D, Williams ED (1983) Studies of X-chromosome inactivation with an improved histochemical technique for ornithine carbamoyltransferase.Histochem J 15: 363–371.

    Google Scholar 

  • Wiesmann U, Colombo JP, Bachmann C (1988) Effect of ammonia on the lysosomal metabolism in brain cell cultures.Enzyme 40(suppl 1): 60 (Abstract).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratoire Central de Chimie Clinique, Centre Hospitalier Universitaire Vaudois, 1011, Lausanne, Switzerland

    C. Bachmann

Authors
  1. C. Bachmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bachmann, C. Ornithine carbamoyl transferase deficiency: Findings, models and problems. J Inherit Metab Dis 15, 578–591 (1992). https://doi.org/10.1007/BF01799616

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01799616

Keywords

Search

Navigation