European Journal of Pediatrics

, Volume 154, Supplement 2, pp S45–S49 | Cite as

Galactose-1-phosphate in the pathophysiology of galactosemia

  • R. Gitzelmann


In galactosemia, galactose-1-phosphate (gal-1-P) is not properly metabolized and accumulates in the fetus and after birth in various tissues when lactose or galactose is ingested. Well-treated galactosemics retain a low level of red cell gal-1-P which increases after breaks of diet. The ester is an indicator of the biogenesis of galactose from glucose and has been considered a pathogenic agent by inhibiting enzymes such as glucose-6-phosphatase, glucose-6-phosphate dehydrogenase, phosphoglucomutase, and glycogen phosphorylase, but the evidence remains presumptive. A futile cycle of galactose phosphorylation and dephosphorylation, and the sequestration of phosphorus in gal-1-P are also suspected to play a role in the pathogenesis of galactosemia.

Key words

Pathophysiology of galactosemia Galactose-1-phosphate uridyltransferase deficiency Endogenous galactose production Self-intoxication with galactose 







inorganic pyrophosphate


uridine diphosphate galactose


uridine diphosphate glucose


uridine triphosphate


  1. 1.
    Berry GT, Palmieri M, Gross KC, Acosta PB, Henstenburg JA, Mazur A, Reynolds R, Segal S (1993) The effect of dietary fruits and vegetables on urinary galactitol excretion in galactose-1-phosphate uridyltransferase deficiency. J Inherited Metab Dis 16:91–100CrossRefPubMedGoogle Scholar
  2. 2.
    Brandt NJ (1980) How long should galactosaemia be treated? In: Burman D, Holton JB, Pennock CA (eds) Inherited disorders of carbohydrate metabolism. MTP Press Ltd., Lancaster, pp 117–124Google Scholar
  3. 3.
    Donnell GN, Koch R, Fishler K, Ng WG (1980) Clinical aspects of galactosaemia. In: Burman D, Holton JB, Pennock CA (eds) Inherited disorders of carbohydrate metabolism. MTP Press Ltd., Lancaster, pp 103–115Google Scholar
  4. 4.
    Forbes GB, Barton LD, Nicholas DL, Cook DA (1988) Composition of milk produced by a mother with galactosemia. J Pediatr 113:90–91Google Scholar
  5. 5.
    Gitzelmann R (1969) Formation of galactose-1-phosphate from uridine diphosphate galactose in erythrocytes from patients with galactosemia. Pediatr Res 3:279–286PubMedGoogle Scholar
  6. 6.
    Gitzelmann R (1980) Newborn screening for inherited disorders of galactose metabolism. In: Bickel H, Guthrie R, Hammersen G (eds) Neonatal screening for inborn errors of metabolism. Springer-Verlag, Berlin Heidelberg New York, pp 67–79Google Scholar
  7. 7.
    Gitzelmann R, Hansen RG (1974) Galactose biogenesis and disposal in galactosemics. Biochim Biophys Acta 372:374–378Google Scholar
  8. 8.
    Gitzelmann R, Hansen RG (1980) Galactose metabolism, hereditary defects and their clinical significance. In: Burman D, Holton JB, Pennock CA (eds) Inherited disorders of carbohydrate metabolism. MTP Press Ltd, Lancaster, pp 61–101Google Scholar
  9. 9.
    Gitzelmann R, Steinmann B (1973) Uridine diphosphate galactose 4-epimerase deficiency. Helv Paediatr Acta 28:497–510PubMedGoogle Scholar
  10. 10.
    Gitzelmann R, Steinmann B (1984) Galactosemia: how does long-term treatment change the outcome? Enzyme 32:37–46Google Scholar
  11. 11.
    Gitzelmann R, Curtius H-C, Schneller I (1967) Galactitol and galactose-1-phosphate in the lens of a galactosemic infant. Exp Eye Res 6:1–3PubMedGoogle Scholar
  12. 12.
    Gitzelmann R, Hansen RG, Steinmann B (1975) Biogenesis of galactose, a possible mechanism of self-intoxication in galactosemia. In: Hommes FA, Van den Berg CJ (eds) Normal and pathological development of energy metabolism. Academic Press, London, pp 25–38Google Scholar
  13. 13.
    Gitzelmann R, Steinmann B, Van den Berghe G (1989) Disorders of fructose metabolism. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease, 6th edn. McGraw-Hill, New York, pp 399–424Google Scholar
  14. 14.
    Gross KC, Acosta PB (1991) Fruits and vegetables are a source of galactose: implications in planning the diets of patients with galactosaemia. J Inherited Metab Dis 14:253–258CrossRefPubMedGoogle Scholar
  15. 15.
    Hansen RG, Gitzelmann R (1975) The metabolism of lactose and galactose. In: Jeanes A, Hodge J (eds) Physiological effects of food carbohydrates. American Chemistry Society, Washington D.C., ACS Symp. Series vol 15, pp 100–122Google Scholar
  16. 16.
    Irons M, Levy HL, Pueschel S, Castree K (1985) Accumulation of galactose-1-phosphate in the galactosemic fetus despite maternal milk avoidance. J Pediatr 107:261–263PubMedGoogle Scholar
  17. 17.
    Isselbacher KJ, Anderson EP, Kurahashi K, Kalckar HM (1956) Congenital galactosemia, a single enzymatic block in galactose metabolism. Science 123:635–636PubMedGoogle Scholar
  18. 18.
    Kalckar HM, Maxwell ES (1958) Biosynthesis and metabolic function of uridine diphosphoglucose in mammalian organisms and its relevance to certain inborn errors. Physiol Rev 38:77–90PubMedGoogle Scholar
  19. 19.
    Kalckar HM, Anderson EP, Isselbacher KJ (1956) Galactosemia, a congenital defect in a nucleotide transferase. Biochim Biophys Acta 20:262–268CrossRefPubMedGoogle Scholar
  20. 20.
    Kalderon B, Dixon RM, Rajagopalan B, Augus PW, Oberhaensli RD, Collins JE, Leonard JV, Radda GK (1992) A study of galactose intolerance in human and rat liver in vivo by31P magnetic resonance spectroscopy. Pediatr Res 32:39–44PubMedGoogle Scholar
  21. 21.
    Kirkman HN, Jr (1993) Galactosemia. Recent developments in newborn screening and enzymatic research. Int Pediatr 8:118–124Google Scholar
  22. 22.
    Kogut MD, Roe TF, Ng W, Donnell GN (1975) Fructose-induced hyperuricemia: observations in normal children and in patients with hereditary dren and in patients with hereditary fructose intolerance and galactosemia. Pediatr Res 9:774–778PubMedGoogle Scholar
  23. 23.
    Komrower GM (1973) Treatment of galactosaemia. In: Seakins JWT, Saunders RA, Toothill C (eds) Treatment of inborn errors of metabolism. Churchill Livingstone, Edinburgh, pp 113–123Google Scholar
  24. 24.
    Lerman S (1960) Pathogenetic factors in experimental galactose cataract. Part I. A.M.A. Arch Ophthalmol 63:128–131PubMedGoogle Scholar
  25. 25.
    Lerman S (1961) Pathogenetic factors in experimental galactose cataract. Part IV. Arch Ophthalmol 65:334–337PubMedGoogle Scholar
  26. 26.
    Maddaiah VT, Madsen NB (1966) Kinetics of purified liver phosphorylase. J Biol Chem 241:3873–3881PubMedGoogle Scholar
  27. 27.
    Mayes JS, Miller LR (1973) The metabolism of galactose by galactosemic fibroblasts in vitro. Biochim Biophys Acta 313:9–16PubMedGoogle Scholar
  28. 28.
    Ng WG, Donnell GN, Bergren WR, Alfi O, Golbus MS (1977) Prenatal diagnosis of galactosemia. Clin Chim Acta 74:227–235CrossRefPubMedGoogle Scholar
  29. 29.
    Ng WG, Xu YK, Kaufman F, Donnell GN (1989) Milk produced by mothers with galactosemia. J Pediatr 115:166–167PubMedGoogle Scholar
  30. 30.
    Nordlie RC (1971) Glucose-6-phosphatase, hydrolytic and synthetic activities. In: Boyer PD (ed) The enzymes, Vol IV. Academic Press, New York, pp 543–610Google Scholar
  31. 31.
    Oliver IT (1961) Inhibitor studies on uridine diphosphoglucose pyrophosphorylase. Biochim Biophys Acta 52:75–81CrossRefPubMedGoogle Scholar
  32. 32.
    Ornstein KS, McGuire EJ, Berry GT, Roth S, Segal S (1992) Abnormal galactosylation of complex carbohydrates in cultured fibroblasts from patients with galactose-1-phosphate uridyltransferase deficiency. Pediatr Res 31:508–511PubMedGoogle Scholar
  33. 33.
    Posternak T (1957) Chemical syntheses of aldohexose-1-phosphates. In: Colowick SP, Kaplan NO (eds) Methods in enzymology, Vol III. Academic Press Inc., New York, pp 129–137Google Scholar
  34. 34.
    Posternak T, Rosselet JP (1954) 31. Action de la phosphoglucomutase du muscle sur des acides aldose-1-phosphoriques. Transformation de l'acid galactose-1-phosphorique. Helv Chim Acta 37:246–250CrossRefGoogle Scholar
  35. 35.
    Roe TF, Hallatt JG, Donnell GN, Ng WG (1971) Childbearing by a galactosemic woman. J Pediatr 78:1026–1030PubMedGoogle Scholar
  36. 36.
    Roth S, McGuire EJ, Roseman S (1971) Evidence for cell-surface glycosyltransferases. J Cell Biol 51:536–547CrossRefPubMedGoogle Scholar
  37. 37.
    Sardharwalla IB, Komrower GM, Schwarz V (1980) Pregnancy in classical galactosaemia. In: Burman D, Holton JB, Pennock CA (eds) Inherited disorders of carbohydrate metabolism. MTP Press Ltd., Lancaster, pp 125–132Google Scholar
  38. 38.
    Schwarz V (1960) The value of galactose phosphate determinations in the treatment of galactosaemia. Arch Dis Child 35:428–432PubMedGoogle Scholar
  39. 39.
    Schwarz V, Golberg L, Komrower GM, Holzel A (1956) Some disturbances of erythrocyte metabolism in galactosaemia. Biochem J 62:34–40PubMedGoogle Scholar
  40. 40.
    Schwarz V, Holzel A, Komrower GM (1958) Laboratory diagnosis of congenital galactosaemia at birth. Lancet I:24–25CrossRefGoogle Scholar
  41. 41.
    Segal S (1993) The challenge of galactosemia. Int Pediatr 8:125–132Google Scholar
  42. 42.
    Sidbury JB Jr (1960) The role of galactose-1-phosphate in the pathogenesis of galactosemia. In: Gardner LI (ed) Molecular genetics and human disease. Charles C Thomas, Springfield, pp 61–82Google Scholar
  43. 43.
    Sidbury JB Jr (1969) Investigations and speculations on the pathogenesis of galactosemia. In: Hsia DY-Y (ed) Galactosemia. Charles C Thomas, Springfield, pp 13–29Google Scholar
  44. 44.
    Tada K (1962) Demonstration of an accumulation of galactose-1-phosphate in the liver from congenital galactosemia. Tohoku J Exp Med 78:1–6PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • R. Gitzelmann
    • 1
  1. 1.Division of Metabolism, Department of PediatricsUniversity of ZürichZürichSwitzerland

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