Disorders of Ornithine and Creatine Metabolism

  • Vivian E. Shih
  • Sylvia Stöckler-Ipsiroglu

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.

Keywords

Torque Creatinine Glycine Proline Lysine 

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References

  1. 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: 170–176PubMedGoogle Scholar
  2. 2.
    Wilson DJ, Weleber RG, Green WR (1991) Ocular clinicopathologic study of gyrate atrophy. Am J Ophthalmol 111:24–33Google Scholar
  3. 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 29:996-1005Google Scholar
  5. 4.
    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 28:979–928Google Scholar
  6. 5.
    Kaiser-Kupfer MI, Kuwabara T, Askanas V (1981) Systemic manifestations of gyrate atrophy of the choroid and retina. Ophthalmology 88: 918–928Google Scholar
  7. 6.
    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: 371PubMedCrossRefGoogle Scholar
  8. 7.
    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: 1428–1433Google Scholar
  9. 8.
    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: 149PubMedCrossRefGoogle Scholar
  10. 9.
    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 32:529–541Google Scholar
  11. 10.
    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: 283–290PubMedCrossRefGoogle Scholar
  12. 11.
    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: 243–251Google Scholar
  13. 12.
    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: 371–378PubMedCrossRefGoogle Scholar
  14. 13.
    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: 513Google Scholar
  15. 14.
    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:2o9Google Scholar
  16. 15.
    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 179–206Google Scholar
  17. 16.
    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 109:1539–1548Google Scholar
  18. 17.
    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: 185–190PubMedCrossRefGoogle Scholar
  19. 18.
    Takki K (1974) Gyrate atrophy of the choroid and retina associated with hyperornithinaemia. Br J Ophthalmol 58: 3PubMedCrossRefGoogle Scholar
  20. 19.
    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: 81–93PubMedGoogle Scholar
  21. 20.
    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: 83PubMedGoogle Scholar
  22. 21.
    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: 717–723Google Scholar
  23. 22.
    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: 364–367CrossRefGoogle Scholar
  24. 23.
    Tuchman M, Knopman DS, Shih VE (1990) Episodic hyperammonemia in adult siblings with hyperornithinemia, hyperammonemia, and homocitrullinuria syndrome. Arch Neurol 47: 1134–1137PubMedCrossRefGoogle Scholar
  25. 24.
    Haust MD, Gordon BA (1987) Possible pathogenetic mechanism in hyperornithinemia, hyperammonemia, and homocitrullinuria syndrome. Birth Defects 23:17–45Google Scholar
  26. 25.
    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: 133–134PubMedCrossRefGoogle Scholar
  27. 26.
    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 5:41Google Scholar
  28. 27.
    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: 90–95PubMedCrossRefGoogle Scholar
  29. 28.
    Gordon BA, Gatfield DP, Haust MD (1987) The hyperornithinemia, hyperammonemia, homocitrullinuria syndrome: an ornithine transport defect remediable with ornithine supplements. Clin Invest Med 10:329–336Google Scholar
  30. 29.
    Hommes FA, Roesel RA (1986) Studies on a case of HHHsyndrome (hyperornithinemia, hyperammonemia and homocitrullinuria). Neuropediatrics 17: 48–52PubMedCrossRefGoogle Scholar
  31. 3o.
    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 131:440–443Google Scholar
  32. 31.
    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: 1652–1655CrossRefGoogle Scholar
  33. 32.
    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: A14Google Scholar
  34. 33.
    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 36:409-413Google Scholar
  35. 34.
    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: 626–631PubMedCrossRefGoogle Scholar
  36. 35.
    Ganesan V, Johnson A, Connelly A, Eckhardt S, Surtees RA (1997) Guanidinoacetate methyltransferase deficiency: new clinical features. Pediatr Neurol 17:155–157Google Scholar
  37. 36.
    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: 136CrossRefGoogle Scholar
  38. 37.
    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: 1189–1193CrossRefGoogle Scholar
  39. 38.
    Hunneman DH, Hanefeld F (1997) GC-MS determination of guanidinoacetate in urine and plasma. J Inherit Metab Dis 20: 450–452PubMedCrossRefGoogle Scholar
  40. 39.
    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 439Google Scholar
  41. 40.
    Jepson JB, Smith I (1953) “Multiple dipping” procedures in paper chromatography: a specific test for hydroxyproline. Nature 172:1100–11o1Google Scholar
  42. 41.
    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: 526–532PubMedCrossRefGoogle Scholar
  43. 42.
    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: 914–922Google Scholar
  44. 43.
    Stockier S, Hanefeld F, Frahm J (1996) Creatine replacement therapy in guanidinoacetate methyltransferase deficiency, a novel inborn error of metabolism. Lancet 348: 789–790CrossRefGoogle Scholar
  45. 44.
    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. 45.
    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: 606–671PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2000

Authors and Affiliations

  • Vivian E. Shih
  • Sylvia Stöckler-Ipsiroglu

There are no affiliations available

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