Skip to main content
SpringerLink
Log in
SpringerLink
Log in

Disorders of Ornithine and Creatine Metabolism

  • Chapter
Inborn Metabolic Diseases

Abstract

Hyperornithinemia due to ornithine aminotransferase (OAT) deficiency is associated with gyrate atrophy (GA) of the choroid and retina. Patients usually become virtually blind by age 55 years. Treatment includes pharmacological doses of pyridoxine (vitamin B6) and/or a low-arginine diet. Preliminary results are encouraging.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 74.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Takahashi O, Hayasaka S, Kiyosawa M, Mizuno K, Saito T et al. (1985) Gyrate atrophy of choroid and retina complicated by vitreous hemorrhage. Jpn J Ophthalmol 29: 170–176

    PubMed  CAS  Google Scholar 

  2. Wilson DJ, Weleber RG, Green WR (1991) Ocular clinicopathologic study of gyrate atrophy. Am J Ophthalmol 111:24–33

    Google Scholar 

  3. Sipila I, Simell R, Rapola J, Sainio K, Tuuteri I (1979) Gyrate atrophy of the choroid and retina with hyperornithinemia:

    Google Scholar 

  4. tubular aggregates and type 2 fiber atrophy in muscle. Neurology 29:996-1005

    Google Scholar 

  5. Arshinoff SA, McCullock JC, Matuk Y, Phillips MJ, Gordon BA, et al. (1979) Amino-acid metabolism and liver ultrastructure in hyperornithinemia with gyrate atrophy of the choroid and retina. Metabolism 28:979–928

    Google Scholar 

  6. Kaiser-Kupfer MI, Kuwabara T, Askanas V (1981) Systemic manifestations of gyrate atrophy of the choroid and retina. Ophthalmology 88: 918–928

    Google Scholar 

  7. Trijbels JMF, Sengers RCA, Bakkaren JAJM et al. (1977) L-Ornithine-ketoacidtransaminase deficiency in cultured fibroblasts of a patient with hyperornithineaemia and gyrate atrophy of the choroid and retina. Clin Chim Acta 79: 371

    Article  PubMed  CAS  Google Scholar 

  8. Vannas-Sulonen K, Simell O, Sipila I (1987) Gyrate atrophy of the choroid and retina. The ocular disease progresses in juvenile patients despite normal or near normal plasma ornithine concentration. Ophthalmology 94: 1428–1433

    Google Scholar 

  9. Shih VE, Mandell R, Herzfeld A (1982) Defective ornithine metabolism in cultured skin fibroblasts from patients with the syndrome of hyperornithinemia, hyperammonemia and homocitrullinuria. Clin Chim Acta 118: 149

    Article  PubMed  CAS  Google Scholar 

  10. Kennaway NG, Weleber RG, Buist NRM (1980) Gyrate atrophy of the choroid and retina with hyperornithinemia: biochemical and histologic studies and repsonse to vitamin B6. Am J Hum Genet 32:529–541

    Google Scholar 

  11. Hayasaka S, Saito T, Nakajima H, Takahashi O, Mizuno K et al. (1985) Clinical trials of vitamin B6 and proline supplementation for gyrate atrophy of the choroid and retina. Br J Ophthalmol 69: 283–290

    Article  PubMed  CAS  Google Scholar 

  12. Shih VE, Berson EL, Gargiulo M (1981) Reduction of hyperornithinemia with a low protein, low arginine diet and pyridoxine in patients with a deficiency of ornithine-ketoacid transaminase ( OKT) activity and gyrate atrophy of the choroid and retina. Clin Chim Acta 113: 243–251

    Google Scholar 

  13. Valle D, Walser M, Brusilow SW, Kaiser-Kupfer M (1980) Gyrate atrophy of the choroid and retina• amino acid metabolism and correction of hyperornithinemia with an arginine-deficient diet. J Clin Invest 65: 371–378

    Article  PubMed  CAS  Google Scholar 

  14. McInnes R, Arshinoff FS, Bell L, Marliss E, McCulloch J (1981) Hyperornithinaemia and gyrate atrophy of the retina. Improvement of vision during treatment with a low-arginine diet. Lancet 1: 513

    Google Scholar 

  15. Berson EL, Hanson AH, Rosner B et al. (1982) A two year trial of low protein, low arginine diets or vitamin B6 for patients with gyrate atrophy. Birth Defects xviii:2o9

    Google Scholar 

  16. Kaiser-Kupfer MI, Valle DL (1987) Clinical, biochemical and therapeutic aspects of gyrate atrophy. In: Osborne N, Chader J (eds) Progress in retinal research, vol 6. Pergamon, Elmsford, NY, pp 179–206

    Google Scholar 

  17. Kaiser-Kupfer MI, Caruso RC, Valle D (1991) Gyrate atrophy of the choroid and retina. Long-term reduction of ornithine slows retinal degeneration. Arch Ophthalmol 109:1539–1548

    Google Scholar 

  18. Wang T, Lawler AM, Steel G, Sipila I, Milam AH et al. (1995) Mice lacking ornithine-6-aminotransferase have paradoxical neonatal hypoornithinaemia and retinal degeneration. Nat Genet 11: 185–190

    Article  PubMed  Google Scholar 

  19. Takki K (1974) Gyrate atrophy of the choroid and retina associated with hyperornithinaemia. Br J Ophthalmol 58: 3

    Article  PubMed  CAS  Google Scholar 

  20. Ramesh V, Gusella JF, Shih VE (1991) Molecular pathology of gyrate atrophy of the choroid and retina due to ornithine aminotransferase deficiency. Mol Biol Med 8: 81–93

    PubMed  CAS  Google Scholar 

  21. Shih VE, Efron ML, Moser HW (1969) Hyperornithinemia, hyperammonemia, and homocitrullinuria: a new disorder of amino acid metabolism associated with myoclonic seizures and mental retardation. Am J Dis Child 117: 83

    PubMed  CAS  Google Scholar 

  22. Shih VE, Laframboise R, Mandell R, Pichette J (1992) Neonatal form of the hyperornithinemia, hyperammonemia and homocitrullinuria ( HHH) syndrome and prenatal diagnosis. Prenat Diagn 12: 717–723

    Google Scholar 

  23. Dionisi Vici C, Bachmann C, Gambarara M, Colombo JP, Sabetta G (1987) Hyperornithinemia-hyperammonemiahomocitrullinuria syndrome: low creatine excretion and effect of citrulline, arginine, or ornithine supplement. Pediatr Res 22: 364–367

    Article  Google Scholar 

  24. Tuchman M, Knopman DS, Shih VE (1990) Episodic hyperammonemia in adult siblings with hyperornithinemia, hyperammonemia, and homocitrullinuria syndrome. Arch Neurol 47: 1134–1137

    Article  PubMed  CAS  Google Scholar 

  25. Haust MD, Gordon BA (1987) Possible pathogenetic mechanism in hyperornithinemia, hyperammonemia, and homocitrullinuria syndrome. Birth Defects 23:17–45

    Google Scholar 

  26. Oyanagi K, Tsuchiyama A, Itakkura Y, Sogawa H, Wagatsuma K et al. (1983) The mechanism of hyperammonaemia and hyperornithinaemia in the syndrome of hyperornithinaemia, hyperammonaemia with homocitrullinuria. J Inherited Metab Dis 6: 133–134

    Article  PubMed  CAS  Google Scholar 

  27. Hommes FA, Ho CK, Roesel RA et al. (1982) Decreased transport of ornithine across the inner mitochondrial membrane as a cause of hyperornithinaemia. J Inherit Metab Dis 5:41

    Google Scholar 

  28. Inoue I, Saheki T, Kayanuma K, Uono M, Nakajima M et al. (1988) Biochemical analysis of decreased ornithine transport activity in the liver mitochondria from patients with hype-rornithinemia, hyperammonemia and homocitrullinuria. Biochim Biophys Acta 964: 90–95

    Article  PubMed  CAS  Google Scholar 

  29. Gordon BA, Gatfield DP, Haust MD (1987) The hyperornithinemia, hyperammonemia, homocitrullinuria syndrome: an ornithine transport defect remediable with ornithine supplements. Clin Invest Med 10:329–336

    Google Scholar 

  30. Hommes FA, Roesel RA (1986) Studies on a case of HHHsyndrome (hyperornithinemia, hyperammonemia and homocitrullinuria). Neuropediatrics 17: 48–52

    Article  PubMed  CAS  Google Scholar 

  31. Zammarchi E, Ciani R, Pasquini E, Bonocore G, Shih VE et al. (1997) Neonatal Onset of Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome with Favourable Outcome. J Pediatr 131:440–443

    Google Scholar 

  32. Am PH, Hauser ER, Thomas GH, Herman G, Hess D et al. (1990) Hyperammonemia in women with a mutation at the ornithine carbamoyltransferase locus: a cause of postpartum coma. N Engl J Med 322: 1652–1655

    Article  Google Scholar 

  33. Camacho J, Biery B, Mitchell G, Almashanu S, Hu C-A et al. (1998) Identification and molecular analysis of the gene responsible for the hyperornithinemia-hyperammonemiahomocitrullinuria ( HHH) syndrome. Am J Hum Genet 63: A14

    Google Scholar 

  34. Stockier S, Holzbach U, Hanefeld F, Marquardt I, Helms G et al. (1994) Creatine deficiency in the brain: a new, treatable inborn error of metabolism. Pediatr Res 36:409-413

    Google Scholar 

  35. Schulze A, Hess T, Wevers R, Mayatepek E, Bachert P et al. (1997) Creatine deficiency syndrome caused by guanidinoacetate methyltransferase deficiency: diagnostic tools for a new inborn error of metabolism. J Pediatr 131: 626–631

    Article  PubMed  CAS  Google Scholar 

  36. Ganesan V, Johnson A, Connelly A, Eckhardt S, Surtees RA (1997) Guanidinoacetate methyltransferase deficiency: new clinical features. Pediatr Neurol 17:155–157

    Google Scholar 

  37. van der Knaap MS, Verhoeven NM, Stuys E, Powels PJW, Jacobs C (1998) Mental retardation and autism as presenting signs in creatine synthesis defect. J Inherit Metab Dis 21: 136

    Article  Google Scholar 

  38. Stockier S, Marescau B, De Deyn PP, Trijbels JM, Hanefeld F (1997) Guanidino compounds in guanidinoacetate methyltransferase deficiency, a new inborn error of creatine synthesis. Metabolism 46: 1189–1193

    Article  Google Scholar 

  39. Hunneman DH, Hanefeld F (1997) GC-MS determination of guanidinoacetate in urine and plasma. J Inherit Metab Dis 20: 450–452

    Article  PubMed  CAS  Google Scholar 

  40. Bremer HJ, Duran M, Kamerling JP, Przyrembel H, Wadman SK (1981) Sakaguchi reaction. Disturbances of amino acid metabolism: clinical chemistry and diagnosis. Urban and Schwarzenberg, Baltimore, p 439

    Google Scholar 

  41. Jepson JB, Smith I (1953) “Multiple dipping” procedures in paper chromatography: a specific test for hydroxyproline. Nature 172:1100–11o1

    Google Scholar 

  42. Marescau B, Deshmukh DR, Kockx M, Possemiers I, Quereshi EA et al. (1992) Guanidinocompounds in serum, urine, liver, kidney, and brain of man and some uretelic animals. Metabolism 41: 526–532

    Article  PubMed  CAS  Google Scholar 

  43. Stockier S, Isbrandt D, Hanefeld F, Schmidt B, von Figura K (1996) Guanidinoacetate methyltransferase deficiency: the first inborn error of creatine metabolism in man. Am J Hum Genet 58: 914–922

    Google Scholar 

  44. Stockier S, Hanefeld F, Frahm J (1996) Creatine replacement therapy in guanidinoacetate methyltransferase deficiency, a novel inborn error of metabolism. Lancet 348: 789–790

    Article  Google Scholar 

  45. Greenhaff PL, Casey A, Short AH, Harris R, Soderlund K et al. (1993) Influence of oral creatine supplementation of muscle torque during repeated bouts of maximal voluntary exercise in man. Clin Sci (Colch) 84565-571

    Google Scholar 

  46. Schulze A, Mayatepek E, Bachert P, Marescau B, De Deyn PP et al. (1998) Therapeutic trial of arginine restriction in creatine deficiency syndrome (letter). Eur J Pediatr 157: 606–671

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. Vivian E. Shih
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sylvia Stöckler-Ipsiroglu
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Veldweg 87, 8051 NP, Hattem, The Netherlands

    John Fernandes (Professor Emeritus of Pediatrics) (Professor Emeritus of Pediatrics)

  2. Hospital Necker-Enfants Malades, 149 Rue de Sevres, 75743, Paris Cedex 15, France

    Jean-Marie Saudubray

  3. Institute of Cellular Pathology, Université Catholique de Louvain, Avenue Hippocrate 75, 1200, Brussels, Belgium

    Georges Van den Berghe (Christian de Duve) (Christian de Duve)

Rights and permissions

Reprints and permissions

Copyright information

© 2000 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Shih, V.E., Stöckler-Ipsiroglu, S. (2000). Disorders of Ornithine and Creatine Metabolism. In: Fernandes, J., Saudubray, JM., Van den Berghe, G. (eds) Inborn Metabolic Diseases. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-04285-4_19

Download citation

  • DOI: https://doi.org/10.1007/978-3-662-04285-4_19

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-04287-8

  • Online ISBN: 978-3-662-04285-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation