Urea Cycle Defects

  • Marjo S. van der Knaap
  • Jacob Valk

Abstract

There are five well-documented urea cycle defects:
  • Carbamyl phosphate synthetase deficiency (CPSD)

  • Ornithine transcarbamylase deficiency (OTCD)

  • Argininosuccinate synthetase deficiency (ASSD), also called citrullinemia

  • Argininosuccinate lyase deficiency (ASLD), also called argininosuccinic aciduria

  • Arginase deficiency, also called hyperargininemia.

Keywords

Lysine Arginine Glutamine Alanine Tryptophan 

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References

  1. Aida S, Ogata T, Kamota T, Nakamura N (1989) Primary ornithine transcarbamylase deficiency. Acta Pathol Jpn 39: 451–456PubMedGoogle Scholar
  2. Bachmann C (1992) Ornithine carbamoyl transferase deficiency:findings, models and problems. J Inherited Metab Dis 15: 578–591PubMedCrossRefGoogle Scholar
  3. Batshaw ML (1994) Inborn errors of urea synthesis. Ann Neurol 35: 133–141PubMedCrossRefGoogle Scholar
  4. Berrez JM, Bardot O, Thiard MC, Alvarez F, Latruff N (1991) Molecular analysis of a human liver mitochondrial ornithine transcarbamylase deficiency. J Inherited Metab Dis 14: 29–36PubMedCrossRefGoogle Scholar
  5. Brockstedt M, Smit LME, de Grauw AJC, 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: 341–343Google Scholar
  6. Bruton CJ, Corsellis JAN, Russell A (1970) Hereditary hyperammonaemia. Brain 93: 423–434PubMedCrossRefGoogle Scholar
  7. Burlina AB, Bachmann C, Wermuth B, Bordugo A, Ferrari V, Colombo JP, Zacchello F (1992) Partial N-acetylglutamate synthetase deficiency:a new case with uncontrollable movement disorders. J Inherited Metab Dis 15: 395–398PubMedCrossRefGoogle Scholar
  8. Carstens RP, Fenton WA, Rosenberg LR (1991) Identification of RNA splicing errors resulting in human ornithine transcarbamylase deficiency. Am J Hum Genet 48: 1105–1114PubMedGoogle Scholar
  9. Christodoulou J, Qureshi IA, McInnes RR, Clarke JTR (1993) Ornithine transcarbamylase deficiency presenting with strokelike episodes. J Pediatr 122: 423–425PubMedCrossRefGoogle Scholar
  10. 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: 77–81PubMedCrossRefGoogle Scholar
  11. Dolman CL, Clasen RA, Dorovini-Zis K (1988) Severe cerebral damage in ornithine transcarbamylase deficiency. Clin Neuropathol 7: 10–15PubMedGoogle Scholar
  12. Donn SM, Thone JG (1985) Prospective prevention of neonatal hyperammonaemia in argininosuccinic acidura by arginine therapy. J Inherited Metab Dis 8: 18–20PubMedCrossRefGoogle Scholar
  13. Feldmann D, Rozet JM, Pelet A, Hentzen D, Briand P, Hubert P, Largilliere C, Rabier D, Farriaux JP, Munnich A (1992) Site specific screening for point mutations in ornithine transcarbamylase deficiency. J Med Genet 29: 471–475PubMedGoogle Scholar
  14. Finkelstein JE, Hauser ER, Leonard CO, Brusilow SW (1990) Late-onset ornithine transcarbamylase deficiency in male patients. J Pediatr 117: 897–902PubMedCrossRefGoogle Scholar
  15. Gallagher JV, Rifai N, Conry J, Soldin SJ (1991) Role of the clinical laboratory in evaluation of argininosuccinate lyase deficiency. Clin Chem 37: 1384–1389PubMedGoogle Scholar
  16. Gerrits GPJM, Gabreëls FJM, Monnens LAH, De Abreu RA, van Raaij-Selten B, Niezen-Koning KE, Trijbels JMF (1993) Arginiosuccinic aciduria:clinical and biochemical findings in three children with the late onset form, with special emphasis on cerebrospinal fluid findings of amino acids and pyrimidines. Neuropediatrics 21: 15–18CrossRefGoogle Scholar
  17. Grody WW, Klein D, Dodson AE, Kern RM, Wissmann PB, Goodman BK, Bassand P, Marescau B, Kang SS, Leonard JV, Cederbaum SD (1992) Molecular genetic study of human arginase deficiency. Am J Hum Genet 50: 1281–1290PubMedGoogle Scholar
  18. 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: 1–5PubMedCrossRefGoogle Scholar
  19. Grompe M, Caskey CT, Fenwick RG (1991) Improved molecular diagnostics for ornithine transcarbamylase deficiency. Am J Hum Genet 48: 212–222PubMedGoogle Scholar
  20. Harding BN, Leonard JV, Erdohazi M (1984) Ornithine carbamoyl transferase deficiency:a neuropathological study. Eur J Pediatr 141: 215–220PubMedCrossRefGoogle Scholar
  21. Häussinger D, Steeb R, Gerok W (1992) Metabolic alkalosis as driving force for urea synthesis in liver disease: pathogenet-Google Scholar
  22. ic model and therapeutic implications. Clin Invest 70:411–415Google Scholar
  23. Hayakawa C, Aono S, Keino H, Mizutani N, Watanabe K, Ikemoto M, Totani M, Murachi T, Kashiwamata S (1991) Absence of erythrocyte arginase protein in Japanese patients with hyperargininemia. Eur J Pediatr 150: 800–803PubMedCrossRefGoogle Scholar
  24. Hommmes FA, de Groot CJ, Wilmink CW, Jonxis JHP (1969) Carbamylphosphate synthetase deficiency in an infant with severe cerebral damage. Arch Dis Child 44: 688–693CrossRefGoogle Scholar
  25. Honeycutt D, Callahan K, Rutledge L, Evans B (1992) Heterozygote ornithine transcarbamylase deficiency presenting as symptomatic hyperammonemia during initiation of valproate therapy. Neurology 42: 666–668PubMedCrossRefGoogle Scholar
  26. Hopkins IJ, Connelly JF, Dawson AG, Hird FJR, Maddison TG (1969) Hyperammonaemia due to ornithine transcarbamylase deficiency. Arch Dis Child 44: 143–148PubMedCrossRefGoogle Scholar
  27. Horiuchi M, Imamura Y, Nakamura N, Maruyama I, Saheki T (1993) Carbamoylphosphate synthetase deficiency in an adult: deterioration due to administration of valproic acid. J Inherited Metab Dis 16: 39–45PubMedCrossRefGoogle Scholar
  28. Hudak ML, Douglas Jones M, Brusilow SW (1985) Differentiation of transient hyperammonemia of the newborn and urea cycle enzyme defects by clinical presentation. J Pediatr 107: 712–719PubMedCrossRefGoogle Scholar
  29. Kendall BE (1992) Disorders of lysosomes, peroxisomes, and mitochondria. AJNR 13: 621–653PubMedGoogle Scholar
  30. Kobayashi K, Itakura Y, Saheki T, Nakano K, Sase M, Oyanagi K, Okamoto R, Mino M (1986) Absence of argininosuccinate lyase protein in the liver of two patients with argininosuccinic aciduria. Clin Chim Acta 159: 59–67PubMedCrossRefGoogle Scholar
  31. Kornfeld M, Woodfin BM, Papile L, Davis LE, Bernard LR (1985) Neuropathology of ornithine carbamyl transferase deficiency. Acta Neuropathol (Berl) 65: 261–264CrossRefGoogle Scholar
  32. Levin B, Abraham JM, Oberholzer VG, Burgess EA (1969) Hyperammonaemia: a deficiency of liver ornithine transcarbamylase. Arch Dis Child 44: 152–161PubMedCrossRefGoogle Scholar
  33. Maestri NE, Hauser ER, Bartholomew D, Brusilow SW (1991) Prospective treatment of urea cycle disorders. J Pediatr 119: 923–928PubMedCrossRefGoogle Scholar
  34. Mamourian AC, du Plessis A (1991) Urea cycle defect: a case with MR and CT findings resembling infarct. Pediatr Radiol 21: 594–595PubMedCrossRefGoogle Scholar
  35. Marescau B, de Deyn PP, Lowenthal A, Qureshi IA, Antonozzi I, Bachmann C, Cederbaum SD, Cerone R, Chamoles N, Colombo JP, Hyland K, Gatti R, Kang SS, Letarte J, Lambert M, Mizutani N, Possemiers I, Rezvani I, Snyderman SE, Terheggen HG, Yoshino M (1990) Guanidino compound analysis as a complementary diagnostic parameter for hyperargininemia: follow-up of guanidino compound levels during therapy. Pediatr Res 27: 297–303PubMedCrossRefGoogle Scholar
  36. Martin JJ, Farriaux JP, De Jonghe P (1982) Neuropathology of citrullinemia. Acta Neuropathol (Berl) 56: 303–306CrossRefGoogle Scholar
  37. Matsuda I, Nagata N, Matsuura T, Oyanagi K, Tada K, Narisawa K, Kitagawa T, Sakiyama T, Yamashita F, Yoshino M (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: 85–89Google Scholar
  38. Matsuura T, Hoshide R, Fukushima M, Sakiyama T, Owada M, Matsuda I (1993a) Prenatal monitoring of ornithine transcarbamoylase deficiency in two families by DNA analysis. J Inherited Metab Dis 16: 31–38PubMedCrossRefGoogle Scholar
  39. Matsuura T, Hoshide R, Setoyama C, Shimada K, Hase Y, Yanagawa T, Kajita M, Matsuda I (1993b) Four novel gene mutations in five Japanese male patients with neonatal or late onset OTC deficiency:application of PCR-single-strand conformation polymorphisms for all exons and adjacent introns. Hum Genet 92: 49–56PubMedCrossRefGoogle Scholar
  40. Mayatepek E, Kurczynski TW, Hoppel CL, Gunning WT (1991) Carnitine deficiency associated with ornithine transcarbamylase deficiency. Pediatr Neurol 7: 196–199PubMedCrossRefGoogle Scholar
  41. McInnes RR, Shih V, Chilton S (1984) Interallelic complementation in an inborn error of metabolism: genetic heterogeneity in argininosuccinate lyase deficiency. Proc Natl Acad Sci U S A 81: 4480–4484PubMedCrossRefGoogle Scholar
  42. Msali M, Batshaw ML, Suss R, Brusilow SW, Mellits ED (1984) Neurologic outcome in children with inborn errors of urea synthesis. N Engl J Med 310: 1500–1505CrossRefGoogle Scholar
  43. Olier J, Gallego J, Digon E (1989) Computerized tomography in primary hyperammonemia. Neuroradiology 31: 356–257PubMedCrossRefGoogle Scholar
  44. Qureshi IA, Letarte J, Ouellet R, Larochelle J, Lemieux B (1983) A new French-Canadian family affected by hyperarginiaemia. J Inherited Metab Dis 6: 179–182PubMedCrossRefGoogle Scholar
  45. Simard L, OBrien WE, McInnes RR (1986) Argininosuccinate lyase deficiency:evidence for heterogeneous structural gene mutations by immunoblotting. Am J Hum Genet 39: 38–51PubMedGoogle Scholar
  46. Slomski R, Braulke I, Behrend C, Schröder E, Colombo JP, Reiss J (1992) Ornithine transcarbamylase ( OTC) deficiency in a female patient with a de novo deletion of the paternal X chromosome. Hum Genet 89: 632–634Google Scholar
  47. Solitare GB, Shih VE, Nelligan DJ, Dolan TF (1969) Argininosuccinic aciduria: clinical, biochemical, anatomical and neuropathological observations. J Ment Defic Res 13: 153170Google Scholar
  48. Strautnicks S, Rutland P, Malcolm S (1991) Arginine 109 to glutamine mutation in a girl with ornithine carbamoyl transferase deficiency. J Med Genet 28: 871–874CrossRefGoogle Scholar
  49. Travers H, Reed JS, Kennedy JA (1986) Ultrastructural study of the liver in argininosuccinase deficiency. Pediatr Pathol 5: 307–318PubMedCrossRefGoogle Scholar
  50. Tsai MY, Holzknecht RA, Tuchman M (1993) Single-strand conformational polymorphism and direct sequencing applied to carrier testing in families with ornithine transcarbamylase deficiency. Hum Genet 91: 321–325PubMedCrossRefGoogle Scholar
  51. Tuchman M (1992) The clinical, biochemical, and molecular spectrum of ornithine transcarbamylase deficiency. J Lab Clin Med 120: 836–850PubMedGoogle Scholar
  52. Tuchman M (1993) Mutations and polymorphisms in the human ornithine transcarbamylase gene. Hum Mutat 2: 174–178PubMedCrossRefGoogle Scholar
  53. Tuchman M, Mauer SM, Holzknecht RA, Summar ML, Vnencak-Jones CL (1992) Prospective versus clinical diagnosis and therapy of acute neonatal hyperammonaemia in two sisters with carbamyl phosphate synthetase deficiency. J Inherited Metab Dis 15: 269–277PubMedCrossRefGoogle Scholar
  54. Uchino T, Haraguchi Y, Aparicio JM, Mizutani N, Higashikawa M, Naitoh H, Mori M, Matsuda I (1992) Three novel mutations in the liver-type arginase gene in three unrelated Japanese patients with argininemia. Am J Hum Genet 51: 1406–1412PubMedGoogle Scholar
  55. Walker DC, McCloskey DA, Simard LR, McInnes RR (1990) Molecular analysis of human argininosuccinate lyase: mutant characterization and alternative splicing of the coding region. Proc Natl Acad Sci U S A 87: 9625–9629PubMedCrossRefGoogle Scholar
  56. Widhalm K, Koch S, Scheibenreiter S, Knoll E, Colombo JP, Bachmann C, Thalhammer 0 (1992) 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 87: 1182–1184Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • Marjo S. van der Knaap
    • 1
  • Jacob Valk
    • 2
  1. 1.Department of Child NeurologyFree University HospitalAmsterdamThe Netherlands
  2. 2.Department of Diagnostic RadiologyFree University HospitalAmsterdamThe Netherlands

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