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Disorders of Ornithine Metabolism

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Inborn Metabolic Diseases

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Abstract

Hyperornithinaemia due to ornithine aminotransferase (OAT) deficiency results in gyrate atrophy of the choroid and retina (GA). Although the progression of the retinal degeneration is highly variable, most GA patients lose all functional vision in middle age (45-65 years). Treatment includes an argininerestricted diet and a trial of pharmacological doses (250-500 mg/day) of pyridoxine (vitamin B). Long-term compliance with an arginine-restricted diet, especially when started at a young age, can reduce ornithine accumulation and slow visual loss and chorioretinal degeneration. Creatine supplementation may be indicated to replenish tissue levels, but this question has not yet been adequately addressed. Rarely, OAT-deficient neonates present with hyperammonaemic encephalopathy due to impaired urea cycle function caused by substrate limitation, with associated hypoargininaemia and hypoornithinaemia.

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References

  1. Valle D, Simell O (2001) The hyperornithinemias. In: Scriver CR, Beaudet AL, Sly WS et al. (eds) The metabolic and molecular bases of inherited disease, 8th edn. McGraw Hill, New York, pp 1857–1895

    Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  4. Valayannopoulos V, Boddaert N, Mention K et al. (2009) Secondary creatine deficiency in ornithine delta-aminotransferase deficiency. Mol Genet Metab 97:109–113

    Article  PubMed  CAS  Google Scholar 

  5. Cleary MA, Dorland L, de Koning TJ et al. (2005) Ornithine aminotransferase deficiency: diagnostic difficulties in neonatal presentation. J Inherit Metab Dis 28:673–679

    Article  PubMed  CAS  Google Scholar 

  6. Webster M, Allen J, Rawlinson D et al. (1999) Ornithine aminotransferase deficiency presenting with hyperammonaemia in a premature newborn. J Inherit Metab Dis 22:80

    Google Scholar 

  7. Champion M, Bird S, Fensom T, Dalton R (2002) Ornithine aminotransferase deficiency (gyrate atrophy) presenting with hyperammonaemic encephalopathy. J Inherit Metab Dis 25 [Suppl 1]:29

    Google Scholar 

  8. Wang T, Lawler AM, Steel G et al. (1995) Mice lacking ornithine-daminotransferase have paradoxical neonatal hypoornithinaemia and retinal degeneration. Nat Genet 11:185–190

    Article  PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  10. Arshinoff SA, McCulloch JC, Matuk Y et al. (1979) Amino-acid metabolism and liver ultrastructure in hyperornithinemia with gyrate atrophy of the choroid and retina. Metabolism 28:979–988

    Article  PubMed  CAS  Google Scholar 

  11. Kaiser-Kupfer MI, Kuwabara T, Askansas V et al. (1981) Systemic manifestations of gyrate atrophy of the choroid and retina. Ophthalmology 88:302

    PubMed  CAS  Google Scholar 

  12. Valtonen M, Näntö-Salonen K, Jääskeläinen S et al. (1999) Central nervous system involvement in gyrate atrophy of the choroids and retina with hyperornithinaemia. J Inherit Metab Dis 22:855–866

    Article  PubMed  CAS  Google Scholar 

  13. Peltola KE, Jaaskelainen S, Heinonen OJ et al. (2002) Peripheral nervous system in gyrate atrophy of the choroid and retina with hyperornithinemia. Neurology 59:735–740

    PubMed  CAS  Google Scholar 

  14. Trijbels JMF, Sengers RCA, Bakkeren JAJM, DeKort AFM, Dutman AF (1977) l-Ornithine-ketoacid-transferase deficiency in cultured fibroblasts of a patient with hyperornithinemia and gyrate atrophy of the choroid and retina. Clin Chim Acta 79: 371

    Article  PubMed  CAS  Google Scholar 

  15. 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

    PubMed  CAS  Google Scholar 

  16. Valle D, Walser M, Brusilow S, 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 

  17. McInnes RR, ArshinoffF SA, Bell L, Marliss EB, McCulloch JC (1981) Hyperornithinaemia and gyrate atrophy of the retina. Improvement of vision during treatment with a low-arginine diet. Lancet 1:513

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  20. 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

    Article  PubMed  CAS  Google Scholar 

  21. Kaiser-Kupfer MI, Caruso RC, Valle D, Reed GF (2004) Use of an arginine-restricted diet to slow progression of visual loss in patients with gyrate atrophy. Arch Ophthalmol 122:982–984

    Article  PubMed  Google Scholar 

  22. Kaiser-Kupfer MI, Caruso RC, Valle D (2002) Gyrate atrophy of the choroid and retina: further experience with long-term reduction of ornithine levels in children. Arch Ophthalmol 120:146–153

    PubMed  Google Scholar 

  23. Santinelli R, Costagliola C, Tolone C et al. (2004) Low-protein diet and progression of retinal degeneration in gyrate atrophy of the choroid and retina: a twenty-six-year follow-up. J Inherit Metab Dis 27:187–196

    Article  PubMed  CAS  Google Scholar 

  24. Heinänen K, Näntö-Salonen K, Komu M et al. (1999) Creatine corrects muscle 31P spectrum in gyrate atrophy with hyperornithinaemia. Eur J Clin Invest 29:1060–1065

    Article  PubMed  Google Scholar 

  25. Shih V, 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 Children 117:83–92

    CAS  Google Scholar 

  26. Shih VE, La Framboise R, Mandell R, Pichette J (1992) Neonatal form of the hyperornithinaemia, hyperammonaemia and homocitrullinuria (HHH) syndrome and prenatal diagnosis. Prenat Diagn 12:717–723

    Article  PubMed  CAS  Google Scholar 

  27. Salvi S, Dionisi-Vici C, Bertini E, Verardo M, Santorelli FM (2001) Seven novel mutations in the ORNT1 gene (SLC25A15) in patients with hyperornithinemia, hyperammonemia, and homocitrullinuria syndrome. Hum Mutat 18:460

    Article  PubMed  CAS  Google Scholar 

  28. Debray FG, Lambert M, Lemieux B et al. (2008) Phenotypic variability among patients with hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrome homozygous for the delF188 mutation in SLC25A15. J Med Genet 45:759–764

    Article  PubMed  CAS  Google Scholar 

  29. Fecarotta S, Parenti G, Vajro P et al. (2006) HHH syndrome (hyperornithinaemia, hyperammonaemia, homocitrullinuria), with fulminant hepatitis-like presentation. J Inherit Metab Dis 29:186–189

    Article  PubMed  CAS  Google Scholar 

  30. Mhanni AA, Chan A, Collison M et al. (2008) Hyperornithinemiahyperammonemia-homocitrullinuria syndrome (HHH) presenting with acute fulminant hepatic failure. J Pediatr Gastroenterol Nutr 46:312–315

    Article  PubMed  CAS  Google Scholar 

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

    Article  Google Scholar 

  32. Smith L, Lambert MA, Brochu P et al. (1992) Hyperornithinemia, hyperammonemia, homocitrullinuria (HHH) syndrome: Presentation as acute liver disease with coagulopathy. J Pediatr Gastroent Nutr 15:431–436

    Article  CAS  Google Scholar 

  33. Al-Hassnan ZN, Rashed MS, Al-Dirbashi OY et al. (2008) Hyperornithinemia- hyperammonemia-homocitrullinuria syndrome with stroke-like imaging presentation: clinical, biochemical and molecular analysis. J Neurol Sci 264:187–194

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  35. Camacho JA, Obie C, Biery B et al. (1999) Hyperornithiemiahyperammonemia- homocitrullinuria (HHH) syndrome is caused by mutations in a gene encoding a mitochondrial ornithine transporter. Nat Genet 22:151–158

    Article  PubMed  CAS  Google Scholar 

  36. Tessa A, Fiermonte G, Dionisi-Vici C et al. (2009) Identification of novel mutations in the SLC25A15 gene in hyperornithinemiahyperammonemia- homocitrullinuria (HHH) syndrome: a clinical, molecular, and functional study. Hum Mutat 30:741–748

    Article  PubMed  CAS  Google Scholar 

  37. Miyamoto T, Kanazawa N, Kato S et al. (2001) Diagnosis of Japanese patients with HHH syndrome by molecular genetic analysis: a common mutation, R179X. J Hum Genet 46:260–262

    Article  PubMed  CAS  Google Scholar 

  38. Metwalli AA, Lammers WL, Van Boekel MA (1998) Formation of homocitrulline during heating of milk. J Dairy Res 65:579–589

    Article  PubMed  CAS  Google Scholar 

  39. 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 118:149–157

    Article  PubMed  CAS  Google Scholar 

  40. Zammarchi E, Ciani F, Pasquini E et al. (1997) Neonatal onset of hyperornithinemia-hyperammonemia-homocitrullinuria syndrome with favorable outcome. J Pediatr 131:440–443

    Article  PubMed  CAS  Google Scholar 

  41. Gaye A, Wong PWK, Kang S, Kolodziej C, Stern A (1983) Treatment of hyperornithinemia, hyperammonemia and homocitrullinuria (HHH) during pregnancy. Clin Res 31:787A

    Google Scholar 

  42. Baumgartner MR, Rabier D, Nassogne MC et al. (2005) Delta1- pyrroline-5-carboxylate synthase deficiency: neurodegeneration, cataracts and connective tissue manifestations combined with hyperammonaemia and reduced ornithine, citrulline, arginine and proline. Eur J Pediatr 164:31–36

    Article  PubMed  CAS  Google Scholar 

  43. Bicknell LS, Pitt J, Aftimos S et al. (2008) A missense mutation in ALDH18A1, encoding delta1-pyrroline-5-carboxylate synthase (P5CS), causes an autosomal recessive neurocutaneous syndrome. Eur J Hum Genet 16:1176–1186

    Article  PubMed  CAS  Google Scholar 

  44. Baumgartner MR, Hu C-A, Almashanu S et al. (2000) Hyperammonemia with reduced ornithine, citrulline, arginine and proline: A new inborn error caused by a mutation in the gene encoding Δ1-pyrroline-5-carboxylate synthase. Hum Molec Genet 9:2853–2858

    Article  PubMed  CAS  Google Scholar 

  45. Wakabayashi Y, Yamada E, Hasegawa T, Yamada R (1991) Enzymological evidence for the indispensability of small intestine in the synthesis of arginine from glutamate. I. Pyrroline-5-carboxylate synthase. Arch Biochem Biophys 291:1–8

    CAS  Google Scholar 

  46. Reversade B, Escande-Beillard N, Dimopoulou A et al. (2009) Mutations in PYCR1 cause cutis laxa with progeroid features. Nat Genet 41:1016–1021

    Article  PubMed  CAS  Google Scholar 

  47. Guernsey DL, Jiang H, Evans SC et al. (2009) Mutation in pyrroline- 5-carboxylate reductase 1 gene in families with cutis laxa type 2. Am J Hum Genet 85:120–129

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Division of Metabolism, University Children’s Hospital, Steinwiesstrasse 75, 8032, Zürich, Switzerland

    Matthias R. Baumgartner

  2. Institute of Genetic Medicine, The Johns Hopkins Hospital, 600 N Wolfe Street, 21287, Baltimore, MD, USA

    David Valle

Authors
  1. Matthias R. Baumgartner
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  2. David Valle
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Editors and Affiliations

  1. Department of Neurology Neurometabolic Unit, Hôpital Pitié Salpêtrière 47–83 Boulevard de l’Hôpital, Paris Cedex 13, 75651, Paris, France

    Jean-Marie Saudubray

  2. Laboratory of Physiological Chemistry de Duve Institute, University of Louvain Medical School, Avenue Hippocrate 75/39, 1200, Brussels, Belgium

    Georges van den Berghe

  3. Biochemical Genetics Unit Manchester Academic Health Science Centre, Central Manchester University Hospitals St Mary’s Hospital, Oxford Road, M13 9WL, Manchester, UK

    John H. Walter

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Baumgartner, M., Valle, D. (2012). Disorders of Ornithine Metabolism. In: Saudubray, JM., van den Berghe, G., Walter, J.H. (eds) Inborn Metabolic Diseases. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-15720-2_22

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  • DOI: https://doi.org/10.1007/978-3-642-15720-2_22

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-15719-6

  • Online ISBN: 978-3-642-15720-2

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