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. 1980 Feb;65(2):371–378. doi: 10.1172/JCI109680

Gyrate atrophy of the choroid and retina: amino acid metabolism and correction of hyperornithinemia with an arginine-deficient diet.

D Valle, M Walser, S W Brusilow, M Kaiser-Kupfer
PMCID: PMC371375  PMID: 7356686

Abstract

Four patients with gyrate atrophy of the choroid and retina were studied, all of whom exhibited the hyperornithinemia characteristic of this disorder. Elevated plasma histidine and diminished plasma lysine and branched-chain amino acids were also noted. The renal clearances of these four amino acids were not sufficiently elevated to explain their low plasma levels. In one subject, an arginine-deficient diet led to progressive reduction in plasma ornithine from 13 times normal to the upper limits of normal, along with the disappearance of ornithinuria and lysinuria. Orally administered alpha-aminoisobutyric acid facilitated the fall in plasma ornithine by increasing renal losses of ornithine. It also increased the clearances of most other amino acids. When plasma ornithine approached normal (less than 200 microM), plasma lysine became normal, plasma arginine became subnormal, and renal clearances of basic amino acids decreased. Long-term (1.5 yr) maintenance with a diet containing 10-20 g of protein plus essential amino acids served to keep plasma ornithine at between 55-355 microM; chorioretinal degeneration did not progress and vision apparently improved.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Batshaw M. L., Bursilow S. W. Asymptomatic hyperammonemia in low birthweight infants. Pediatr Res. 1978 Mar;12(3):221–224. doi: 10.1203/00006450-197803000-00012. [DOI] [PubMed] [Google Scholar]
  2. Berson E. L., Schmidt S. Y., Rabin A. R. Plasma amino-acids in hereditary retinal disease. Ornithine, lysine, and taurine. Br J Ophthalmol. 1976 Feb;60(2):142–147. doi: 10.1136/bjo.60.2.142. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Berson E. L., Schmidt S. Y., Shih V. E. Ocular and biochemical abnormalities in gyrate atrophy of the choroid and retina. Ophthalmology. 1978 Oct;85(10):1018–1027. doi: 10.1016/s0161-6420(78)35588-3. [DOI] [PubMed] [Google Scholar]
  4. CROFFORD O. B., FELTS P. W., LACY W. W. EFFECT OF GLUCOSE INFUSION ON THE INDIVIDUAL PLASMA FREE AMINO ACIDS IN MAN. Proc Soc Exp Biol Med. 1964 Oct;117:11–14. doi: 10.3181/00379727-117-29483. [DOI] [PubMed] [Google Scholar]
  5. Christensen H. N., Cullen A. M. Effects of non-metabolizable analogs on the distribution of amino acids in the rat. Biochim Biophys Acta. 1968 Mar 1;150(2):237–252. doi: 10.1016/0005-2736(68)90167-3. [DOI] [PubMed] [Google Scholar]
  6. Falchuk Z. M., Edwards W. A., Laster L. Effects of alpha-aminoisobutyric acid on urinary excretion of homocystine in patients with homocystinuria. Metabolism. 1973 Apr;22(4):605–610. doi: 10.1016/0026-0495(73)90074-7. [DOI] [PubMed] [Google Scholar]
  7. Fell V., Pollitt R. J. 3-Aminopiperid-2-one, an unusual metabolite in the urine of a patient with hyperammonaemia, hyperornithinaemia and homocitrullinuria. Clin Chim Acta. 1978 Aug 1;87(3):405–409. doi: 10.1016/0009-8981(78)90185-7. [DOI] [PubMed] [Google Scholar]
  8. Giordano C., De Santo N. G., Pluvio M., Santinelli R., Stoppoloni G. Lysine in treatment of hyperornithinemia. Nephron. 1978;22(1-3):97–106. doi: 10.1159/000181428. [DOI] [PubMed] [Google Scholar]
  9. Kaiser-Kupfer M. I., Valle D., Del Valle L. A. A specific enzyme defect in gyrate atrophy. Am J Ophthalmol. 1978 Feb;85(2):200–204. doi: 10.1016/s0002-9394(14)75948-3. [DOI] [PubMed] [Google Scholar]
  10. Kennaway N. G., Weleber R. G., Buist N. R. Gyrate atrophy of choroid and retina: deficient activity of ornithine ketoacid aminotransferase in cultured skin fibroblasts. N Engl J Med. 1977 Nov 24;297(21):1180–1180. doi: 10.1056/nejm197711242972116. [DOI] [PubMed] [Google Scholar]
  11. McCulloch C., Marliss E. B. Gyrate atrophy of the choroid and retina with hyperornithinemia. Am J Ophthalmol. 1975 Dec;80(6):1047–1057. doi: 10.1016/0002-9394(75)90335-9. [DOI] [PubMed] [Google Scholar]
  12. McCulloch J. C., Arshinoff S. A., Marliss E. B., Parker J. A. Hyperornithinemia and gyrate atrophy of the choroid and retina. Ophthalmology. 1978 Sep;85(9):918–928. doi: 10.1016/s0161-6420(78)35598-6. [DOI] [PubMed] [Google Scholar]
  13. Mudd S. H., Poole J. R. Labile methyl balances for normal humans on various dietary regimens. Metabolism. 1975 Jun;24(6):721–735. doi: 10.1016/0026-0495(75)90040-2. [DOI] [PubMed] [Google Scholar]
  14. Oberholzer V. G., Briddon A. 3-Amino-2-piperidone in the urine of patients with hyperornithinemia. Clin Chim Acta. 1978 Aug 1;87(3):411–415. doi: 10.1016/0009-8981(78)90186-9. [DOI] [PubMed] [Google Scholar]
  15. ROBSON E. B., ROSE G. A. The effect of intravenous lysine on the renal clearances of cystine, arginine and ornithine in normal subjects, in patients with cystinuria and Fanconi syndrome and in their relatives. Clin Sci. 1957 Feb;16(1):75–93. [PubMed] [Google Scholar]
  16. ROSE W. C., HAINES W. J., WARNER D. T. The amino acid requirements of man. V. The rôle of lysine, arginine, and tryptophan. J Biol Chem. 1954 Jan;206(1):421–430. [PubMed] [Google Scholar]
  17. Ross G., Dunn D., Jones M. E. Ornithine synthesis from glutamate in rat intestinal mucosa homogenates: evidence for the reduction of glutamate to gamma-glutamyl semialdehyde. Biochem Biophys Res Commun. 1978 Nov 14;85(1):140–147. doi: 10.1016/s0006-291x(78)80021-7. [DOI] [PubMed] [Google Scholar]
  18. SNYDERMAN S. E., BOYER A., HOLT L. E., Jr The arginine requirement of the infant. AMA J Dis Child. 1959 Feb;97(2):192–195. doi: 10.1001/archpedi.1959.02070010194006. [DOI] [PubMed] [Google Scholar]
  19. STRECKER H. J. PURIFICATION AND PROPERTIES OF RAT LIVER ORNITHINE DELTA-TRANSAMINASE. J Biol Chem. 1965 Mar;240:1225–1230. [PubMed] [Google Scholar]
  20. Shih V. E., Berson E. L., Mandell R., Schmidt S. Y. Ornithine ketoacid transaminase deficiency in gyrate atrophy of the choroid and retina. Am J Hum Genet. 1978 Mar;30(2):174–179. [PMC free article] [PubMed] [Google Scholar]
  21. Simell O., Perheentupa J. Renal handling of diamino acids in lysinuric protein intolerance. J Clin Invest. 1974 Jul;54(1):9–17. doi: 10.1172/JCI107753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Simell O., Takki K. Raised plasma-ornithine and gyrate atrophy of the choroid and retina. Lancet. 1973 May 12;1(7811):1031–1033. doi: 10.1016/s0140-6736(73)90667-3. [DOI] [PubMed] [Google Scholar]
  23. Smith A. D., Benziman M., Strecker H. J. The formation of ornithine from proline in animal tissues. Biochem J. 1967 Aug;104(2):557–563. doi: 10.1042/bj1040557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Snyderman S. E., Sansaricq C., Norton P. M., Goldstein F. Argininemia treated from birth. J Pediatr. 1979 Jul;95(1):61–63. doi: 10.1016/s0022-3476(79)80082-7. [DOI] [PubMed] [Google Scholar]
  25. Takki K., Simell O. Gyrate atrophy of the choroid and retina with hyperornithinemia HOGA. Birth Defects Orig Artic Ser. 1976;12(3):373–384. [PubMed] [Google Scholar]
  26. Trijbels J. M., Sengers R. C., Bakkeren J. A., De Kort A. F., Deutman A. F. L-Ornithine-ketoacid-transaminase deficiency in cultured fibroblasts of a patient with hyperornithinaemia and gyrate atrophy of the choroid and retina. Clin Chim Acta. 1977 Sep 1;79(2):371–377. doi: 10.1016/0009-8981(77)90431-4. [DOI] [PubMed] [Google Scholar]
  27. Valle D., Kaiser-Kupfer M. I., Del Valle L. A. Gyrate atrophy of the choroid and retina: deficiency of ornithine aminotransferase in transformed lymphocytes. Proc Natl Acad Sci U S A. 1977 Nov;74(11):5159–5161. doi: 10.1073/pnas.74.11.5159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Walser M., Batshaw M., Sherwood G., Robinson B., Brusilow S. Nitrogen metabolism in neonatal citrullinaemia. Clin Sci Mol Med. 1977 Aug;53(2):173–181. doi: 10.1042/cs0530173. [DOI] [PubMed] [Google Scholar]
  29. Walser M., Coulter A. W., Dighe S., Crantz F. R. The effect of keto-analogues of essential amino acids in severe chronic uremia. J Clin Invest. 1973 Mar;52(3):678–690. doi: 10.1172/JCI107229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Weleber R. G., Kennaway N. G., Buist N. R. Vitamin B6 in management of gyrate atrophy of choroid and retina. Lancet. 1978 Dec 2;2(8101):1213–1213. doi: 10.1016/s0140-6736(78)92211-0. [DOI] [PubMed] [Google Scholar]

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