Advertisement

Inborn errors of carnosine and homocarnosine metabolism

  • L. R. Gjessing
  • H. A. Lunde
  • L. MØrkrid
  • J. F. Lenney
  • O. Sjaastad
Part of the Journal of Neural Transmission book series (NEURAL SUPPL, volume 29)

Summary

Serum carnosinase deficiency with carnosinuria has been reported in 23 children with neurological signs and/or mental retardation. In adults four cases in one family had serum carnosinase deficiency, carnosinuria, and in addition elevated homocarnosine in CSF and in the brain. The mother was one of these cases but had no clinical symptoms; however her three children have spastic paraparesis, retinitis pigmentosa and mental retardation. Serum carnosinase deficiency alone is not the cause of the neurological symptoms. When two of the affected children consumed carnosine, anserine or homocarnosine, they metabolized these compounds much less rapidly than did two normal control individuals.

Keywords

Retinitis Pigmentosa Inborn Error Retinal Pigmentation Urea Cycle Defect Normal Control Individual 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abraham D, Pisano JJ, Udenfriend S (1962) The distribution of homocarnosine in mammals. Arch Biochem Biophys 99: 210–213.PubMedCrossRefGoogle Scholar
  2. Ames BN (1983) Dietary carcinogens and anticarcinogens. Oxygen radicals and degenerative diseases. Science 221: 1256–1264.PubMedCrossRefGoogle Scholar
  3. Bessman SP, Baldwin R (1962) Imidazole aminoaciduria in cerebromacular degeneration. Science 135: 789–791.PubMedCrossRefGoogle Scholar
  4. Burgess EA, Oberholzer VG, Palmer T, Levin B (1975) Plasma carnosinase deficiency in patients with urea cycle defects. Clin Chim Acta 61: 215–218.PubMedCrossRefGoogle Scholar
  5. Cohen M, Hartlage PL, Krawiecki N, Roesel RA, Carter AL, Hommes FA (1985) Serum carnosinase deficiency: a non-disabling phenotype? J Ment Defic Res 29: 383–389.PubMedGoogle Scholar
  6. Crush KG (1970) Carnosine and related substances in animal tissues. Comp Biochem Physiol 34: 3–30.PubMedCrossRefGoogle Scholar
  7. Efron M (1969) High voltage paper electrophoresis. In: Smith I (ed) Chromatographic and electrophoretic techniques, vol 2: Zone electrophoresis. William Heinemann, Medical Books, London, p 158.Google Scholar
  8. Fleischer LD, Rassin DK, Wisniewski K, Salwen HF (1980) Carnosinase deficiency: a new variant with high residual activity. Pediatr Res 14: 269–271.Google Scholar
  9. Gjessing LR, Sjaastad O (1974) Homocarnosinosis, a new metabolic disorder associated with spasticity and mental retardation. Lancet ii: 1028.CrossRefGoogle Scholar
  10. Gordon EF, Coulombe JT, Sepe SJ, Levy HL (1977) A variant with carnosinemia with normal serum carnosinase activity in an infant. Pediatr Res 11: 456.CrossRefGoogle Scholar
  11. Haegele KD, Schwartz JJ, Schoun J, Schmitt AH, Schechter PJ (1987) 2 Pyrrolidinone in human cerebrospinal fluid: a major constituent of total-γ-aminobutyric acid. J Neu-rochem 49: 1402–1406.Google Scholar
  12. Hartlage PL, Roesel RA, Eller AG, Hommes FA (1982) Serum carnosinase deficiency: decreased affinity of the enzyme for the substrate. J Inher Metab Dis 5: 13–14.CrossRefGoogle Scholar
  13. Kohen R, Yamamoto Y, Cundy KC, Ames BN (1988) Antioxidant activity of carnosine, homocarnosine, and anserine present in muscle and brain. Proc Natl Acad Sci 85: 3175–3179.PubMedCrossRefGoogle Scholar
  14. Leininger ML, Chapay P, Charvet J, Vovave L, Louchet E (1980) La carnosinémie. Premiére observation francaise. Pédiatrie 35: 341.PubMedGoogle Scholar
  15. Lenney JF, Peppers SC, Kucera CM, Sjaastad O (1983) Homocarnosinosis: lack of serum carnosinase is the defect probably responsible for elevated brain and CSF homocarnosine. Clin Chim Acta 132: 157–165.PubMedCrossRefGoogle Scholar
  16. Lenney JF (1985) Carnosinase and homocarnosinosis. J Oslo City Hosp 35: 21–46.Google Scholar
  17. Lenney JF (1988) unpublished data.Google Scholar
  18. Levenson J, Lindahl-Kiessling K, Rayner S (1964) Carnosine excretion in juvenile amaurotic idiocy. Lancet ii: 756.CrossRefGoogle Scholar
  19. Lunde HA, Sjaastad O, Gjessing L (1982) Homocarnosinosis: hypercarnosinuria. J Neu-rochem 38: 242–245.Google Scholar
  20. Lunde HA, Gjessing LR, Sjaastad O (1986) Homocarnosinosis: influence of dietary restriction of histidine. Neurochem Res 11 (6): 825–838.PubMedCrossRefGoogle Scholar
  21. Lunde HA, Lenney JF, Halvorsen S, Gjessing L (1987) Serum carnosinase in blood and homocarnosine in CSF of patients with Følling’s disease (PKU). J Oslo City Hosp 37: 29–33.PubMedGoogle Scholar
  22. Margolis FL, Grillo M, Grannot-Reisfeld N, Farbman AI (1983) Purification, characterization and immunocytochemical localization of mouse kidney carnosinase. Biochim Biophys Acta 744: 237–248.PubMedCrossRefGoogle Scholar
  23. Murphy WH, Lindmark DG, Patchen L, Housler ME, Harrod EK, Mosovich L (1973) Serum carnosinase deficiency concomitant with mental retardation. Pediatr Res 7: 601–606.Google Scholar
  24. Perry TL, Hansen S, Tischler B, Bunting R, Berry K (1967) Carnosinemia: a new metabolic disorder associated with neurological disease and mental defect. N Engl J Med 277: 1219–1227.PubMedCrossRefGoogle Scholar
  25. Perry TL, Hansen S, Lowe DL (1968) Serum carnosinase deficiency in carnosinemia. Lancet i: 1229.CrossRefGoogle Scholar
  26. Perry TL, Kish SJ, Sjaastad O, Gjessing LR, Nesbakken R, Schrader H, Løken AC (1979) Homocarnosinosis: increased content of homocarnosine and deficiency of homocar-nosinase in brain. J Neurochem 32: 1637–1640.PubMedCrossRefGoogle Scholar
  27. Perry TL, Hansen S, Wau RA, Gauthier SG (1982) Human CSF GABA concentrations, revised downward for controls but not decreased in Huntington’s chorea. J Neurochem 38: 766–773.PubMedCrossRefGoogle Scholar
  28. Pisano JJ, Wilson JD, Cohen L, Abraham D, Udenfriend S (1961) Isolation of γ amino-butyrylhistidine (homocarnosine) from brain. J Biol Chem 236: 499–502.PubMedGoogle Scholar
  29. Rochel S, Margolis FL (1982) Carnosine release from olfactory bulb synaptosomes is calcium-dependent and depolarization stimulated. J Neurochem 38: 1505–1514.PubMedCrossRefGoogle Scholar
  30. Roesel RA, Hartlage P, Hall WK (1981) Carnosinuria and serum carnosinase deficiency in a child with congenital myopathy. Fed Proc 40: 86.Google Scholar
  31. Scriver CR, Perry TL, Nutzenadel W (1983) Disorders of β-alanine, carnosine and homocarnosine metabolism. In: Stanbury JB, Wyngaarden JB, Fredrickson DS, Goldstein JL, Brown MS (eds) The metabolic basis of inherited disease, 5th edn. McGraw-Hill, New York, pp 570–585.Google Scholar
  32. Sjaastad O, Berstad J, Gjesdahl P, Gjessing L (1976) Homocarnosinosis 2. A familial metabolic disorder associated with spastic paraplegia, progressive mental deficiency and retinal pigmentation. Acta Neurol Scand 52: 275–290.CrossRefGoogle Scholar
  33. Sjaastad O, Gjessing L, Berstad J, Gjesdahl P (1977) Homocarnosinosis 3. Spinal fluid amino acids in familial spastic paraplegia. Acta Neurol Scand 55: 158–162.PubMedCrossRefGoogle Scholar
  34. Smith I (1960) Aminoacids, amines and related compounds. In: Smith I (ed) Chromatographic and electrophoretic techniques, vol 1. Chromatography. W Heinemann Medical Books, London, p 82.Google Scholar
  35. Terplan KL, Cares HL (1972) Histopathology of the nervous system in carnosinase enzyme deficiency with mental retardation. Neurology 22: 644–655.PubMedGoogle Scholar
  36. Undrum T, Gjessing LR (1982) unpublished data.Google Scholar
  37. Undrum T, Lunde HA, Gjessing LR (1982) Determination of ophidine in human urine. J Chromatogr 227: 53–59.PubMedCrossRefGoogle Scholar
  38. van Heeswijk PJ, Trijbels JMF, Schretlen EDAM, van Munster PJJ, Monnens LAH (1969) A patient with a deficiency of serum-carnosinase activity. Acta Paediat Scand 58: 584–592.PubMedCrossRefGoogle Scholar
  39. van Sande M, Mardens Y, Adriaenssens K, Lowenthal A (1970) The free amino acids in human cerebrospinal fluid. J Neurochem 17: 125–136.PubMedCrossRefGoogle Scholar
  40. Westall RG (1955) Amino acids and other ampholytes of urine. Biochem J 60: 247–255.PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • L. R. Gjessing
    • 1
    • 4
  • H. A. Lunde
    • 1
  • L. MØrkrid
    • 1
  • J. F. Lenney
    • 2
  • O. Sjaastad
    • 3
  1. 1.Neurochemical Research Laboratory, Institute of NeuropsychiatryDikemark Hospital, Asker, SolbergNorway
  2. 2.Department of Pharmacology, School of MedicineUniversity of HawaiiHonoluluUSA
  3. 3.Department of NeurologyTrondheim University HospitalTrondheimNorway
  4. 4.Neurochemical Research Laboratory, Institute of NeuropsychiatryDikemark Hospital, AskerSolbergNorway

Personalised recommendations