Skip to main content
Log in

Komrower Lecture: Galactosaemia today: The enigma and the challenge

  • Published:
Journal of Inherited Metabolic Disease

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

REFERENCES

  • Anonymous (1982) Clouds over galactosaemia. Lancet II: 1379–1380.

  • Baker L, Mellman WJ, Tedesco TA, Segal S (1966) Galactosaemia: symptomatic and asymptomatic homozygotes in one Negro sibship. J Pediatrics 68: 551–558.

    Google Scholar 

  • Bakker HD, Boelen CCA (1993) Clinical and biochemical study of 69 cases of classical galactosaemia in the Netherlands. Int Pediatr 8: 135–136.

    Google Scholar 

  • Bergren W, Ng W, Donnell G (1972) Galactonic acid in galactosaemia: identification in the urine. Science 176: 683–684.

    Google Scholar 

  • Berry GT (1995) The role of polyols in the pathophysiology of galactosaemia. Eur J Pediatr 154(supplement 2): S53-S64.

    Google Scholar 

  • Berry GT, Palmieri MJ, Gross KC, et al (1993) The effects of dietary fruits and vegetables on urinary galactitol excretion in galactose-1-phosphate uridyltransferase deficiency. J Inher Metab Dis 16: 91–100.

    Google Scholar 

  • Berry GT, Nissim I, Mazur AT, et al (1995a) In vivo oxidation of [13C]galactose in patients with galactose-1-phosphate uridyltransferase deficiency. Biochem Mol Med 56: 158–165.

    Google Scholar 

  • Berry GT, Nissim I, Lin Z, Mazur AT, Gibson JB, Segal S (1995b) Endogenous synthesis of galactose in normal man and patients with hereditary galactosaemia. Lancet 346: 1073–1074.

    Google Scholar 

  • Berry GT, Nissim I, Gibson JB, et al (1997) Quantitative assessment of whole body galactose metabolism in galactosemic patients. Eur J Pediatr 156:(supplement 1): S43-S49.

    Google Scholar 

  • Beutler E, Baluda MC, Sturgeon P, Day RW (1965) A new genetic abnormality resulting in galactose-1-phosphate uridyltransferase deficiency. Lancet 1: 353–355.

    Google Scholar 

  • Beutler E, Boluda MC, Sturgeon P, Day RW (1966) The genetics of galactose-1-phosphate uridyltransferase deficiency. J L ab Clin Med 68: 646–658.

    Google Scholar 

  • Cuatrecasas P, Segal S (1966) Galactose conversion to D-xylulose: An alternate route of galactose metabolism. Science 153: 549–551.

    Google Scholar 

  • Dobbie JA, Holton JB, Clamp JR (1990) Defective galactosylation of proteins in cultured skin fibroblasts from galactosemic patients. Ann Clin Biochem 27: 274–275.

    Google Scholar 

  • Elsas LJ II, Friedovich-Keil JL, Leslie N (1993) Galactosaemia: a molecular approach to the enigma. Int Pediatr 8: 101–109.

    Google Scholar 

  • Elsas LJ II, Dembure PP, Langley S, Paulk EM, Hjelms LN, Fridovich-Keil JL (1994) A common mutation associated with the Duarte galactosaemia allele. Am J Hum Genet 54: 1030–1031.

    Google Scholar 

  • Elsas LJ II, Langley S, Paulk EM, Hjelm LN, Dembure PP (1995) A molecular approach to galactosaemia. Eur J Pediatr 154(supplement 2): 521–527.

    Google Scholar 

  • Flach JE, Reichert JKV, Elsas LJ (1990) Sequence of a cDNA encoding human galactose-1-phosphate uridyltransferase gene. Mol Biol Med 7: 365–369.

    Google Scholar 

  • Fridovich-Keil JL, Jinks-Robertson S (1993) A yeast expression system for human galactose-1-phosphate uridyltransferase. Proc Natl Acad Sci USA 90: 398–402.

    Google Scholar 

  • Gibson JB, Reynolds RA, Palmieri MJ, States B, Berry GT, Segal S (1994) UDPhexoses in leukocytes and fibroblasts of classic galactosemics and patients with other metabolic diseases. Pediatr Res 36: 613–618.

    Google Scholar 

  • Gibson JB, Reynolds RA, Palmieri MJ, et al (1995) Comparison of erythrocyte uridine sugar nucleotide levels in normals, classic galactosemics and patients with other metabolic disorders. Metabolism 44: 597–604.

    Google Scholar 

  • Gitzelmann R (1969) Formation of galactose-1-phosphate from uridine diphosphate galactose in erythrocytes from patients and galactosemics. Pediatr Res 3: 279–286.

    Google Scholar 

  • Gitzelmann R, Hansen RG (1974) Galactose biogenesis and disposal in galactosemics. Biochim Biophys Acta 372: 374–378.

    Google Scholar 

  • Haberland C, Perou M, Brunngraber EG (1971) The neuropathology of galactosaemia: a histopathological and biochemical study. J Neuropathol Exp Neurol 30: 431–437.

    Google Scholar 

  • Hayman S, Kinoshita JH (1965) Isolation and properties of lens aldose reductase. J Biol Chem 240: 877–882.

    Google Scholar 

  • Heidenreich RA, Mallee J, Rogers S, Segal S (1994) Developmental and tissue specific modulation of rat galactose-1-phosphate uridyltransferase steady-state mRNA and specific activity levels. Pediatr Res 34: 416–419.

    Google Scholar 

  • Hers HG (1960) Le mechanisme de la formation du fructose seminal et du fructose fetal. Biochim Biophys Acta 37: 127–138.

    Google Scholar 

  • Holzel A, Komrower GM (1955) Study of the genetics of galactosaemia. Arch Dis Child 30: 155–159.

    Google Scholar 

  • Jaeken J, Kint J, Spaaken L (1992) Serum lysosomal enzyme abnormalities in galactosaemia. Lancet 340: 1472–1473.

    Google Scholar 

  • Jakobs C, Schweitzer S, Dorland B (1995) Galactitol in galactosaemia. Eur J Pediatr 154(supplement 2) S50-S52.

    Google Scholar 

  • Kaufman FR, Reichardt JR, Ng WG, et al (1994) Correlation of cognitive, neurologic and ovarian outcome with the Q188R mutation of the galactose-1-phosphate uridyltransferase. J Pediatr 125: 225–227.

    Google Scholar 

  • Kaufman FR, McBride-Chang C, Manis FR, Wol. JA, Nelson MD (1995) Cognitive functioning, neurologic status and brain imaging in classic galactosaemia. Eur J Pediatr 154(supplement 2): S2-S5.

    Google Scholar 

  • Keevill NJ, Holton JB, Allen JT (1994) UDPglucose and UDPgalactose concentrations in cultured skin fibroblasts of patients with classic galactosaemia. J Inher Metab Dis 17: 23–26.

    Google Scholar 

  • Kirkman HN, Bynum E (1959) Enzymatic evidence of a galactosemic trait in parents of galactosemic children. Ann Hum Genet 23: 117.

    Google Scholar 

  • Komrower GM (1982) Galactosaemia, 30 years on: the experience of a generation. J Inher Metab Dis 5(supplement 2): 96–104.

    Google Scholar 

  • Komrower GM, Lee DH (1970) Long-term follow up of galactosaemia. Arch Dis Child 45: 367–373.

    Google Scholar 

  • Komrower GM, Schwarz V, Holzel A, Golberg A (1956) A clinical and biochemical study of galactosaemia: a possible explanation for the nature of the biochemical lesion. Arch Dis Child 31: 254–264.

    Google Scholar 

  • Lai K, Langley SD, Singh R, Dembure PP, Hjelm LN, Elsas LJ (1996) A prevalent mutation for galactosaemia among Black Americans. J Pediatr 128: 89–95.

    Google Scholar 

  • Lai K, Langley SD, Dembure PP, Hjelm LN, Elsas LJ (1998) The Duarte allele impairs biostability of galactose-1-phosphate uridyltransferase in human lymphoblasts. Hum Mutat, 11: 28–38.

    Google Scholar 

  • Leslie ND, Immerman EB, Flach JE, Florez M, Fridovich-Keil JL, Elsas LJ (1992) The human galactose-1-phosphate uridyltransferase gene. Genomics 14: 474–480.

    Google Scholar 

  • Leslie ND, Yager CL, McNamara PD, Segal S (1996) A mouse model of galactose-1-phosphate uridyltransferase deficiency. Biochem Mol Med 59: 7–12.

    Google Scholar 

  • Levy HL, Sepe SJ, Walton DS, et al (1978) Galactose-1-phosphate uridyltransferase deficiency due to Duarte galactosaemia combined variation clinical and biochemical studies. J Pediatr 92: 390–393.

    Google Scholar 

  • Mason HH, Turner ME (1935) Chronic galactosaemia. Am J Dis Child 50: 359–374.

    Google Scholar 

  • Nelson MD, Wolff JA, Cross CA, Donnell GN, Kaufman FR (1982) Galactosemia: evaluation with MR imagining. Radiology 184: 255–261.

    Google Scholar 

  • Ng WG, Xu YK, Kaufman FR, et al (1994) Biochemical and molecular studies of 132 patients with galactosaemia. Hum Genet 94: 359–363.

    Google Scholar 

  • 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: 508–511.

    Google Scholar 

  • Palmieri MJ, Berry GT, Player DA, Rogers S, Segal S (1991) The concentration of red blood cell UDPglucose and UDPgalactose determined by high performance liquid chromatography. Anal Biochem 194: 388–393.

    Google Scholar 

  • Petry K, Greinix HT, Nudelman E, Eisen H, Hakomori S-I, Levy HL, Reichardt JK (1991) Characterization of a novel biochemical abnormality in galactosaemia: deficiency of glycolipids containing galactose or N-acetylgalactosamine and accumulation of precursors in brain and lymphocytes. Biochem Med Metab Biol 46: 93–104.

    Google Scholar 

  • Prestoz LLC, Couto AS, Shin YS, Petry KG (1997) Alternate follicle stimulating hormone isoforms in female galactosemics. Eur J Pediatr 156: 116–120.

    Google Scholar 

  • Rancour NJ, Hawkins ED, Wells WW (1979) Galactose oxidation in liver. Arch Biochem Biophys 193:232–241.

    Google Scholar 

  • Schwarz HP, Schaefer T, Bachmann C (1985) Galactose and galactitol in the urine of children with compound heterozygosity for Duarte variant and classical galactosaemia (GTD/qt) after an oral galactose load. Clin Chem 31: 420–422.

    Google Scholar 

  • Schwarz HP, Zappenger KA, Zimmerman A, Danwalder H, Scherz H, Bier DM (1982) Galactose intolerance in individuals with double heterozygosity for Duarte variant and galactosaemia. J Pediatr 100: 704–709.

    Google Scholar 

  • Schwarz V, Golberg L, Komrower GM, Holzel A (1956) Some disturbances of erythrocyte metabolism in galactosaemia. Biochem J 62: 34–40.

    Google Scholar 

  • Schweitzer S, Shin Y, Jakobs C, Brodell J (1993) Long-term outcome of 134 patients with galactosaemia. Eur J Pediatr 152: 36–43.

    Google Scholar 

  • Segal S (1995) Defective galactosylation in galactosemia: is there low cell UDPgalactose as an explanation? Eur J Pediatr 154(supplement 2): S65-S71.

    Google Scholar 

  • Segal S, Berry GT (1995) Disorders of galactose metabolism. In Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Diseases, 7th edn. New York: McGraw-Hill, 967–1000.

    Google Scholar 

  • Segal S, Cuatrecasas P (1968) The oxidation of 14Cgalactose by patients with congenital galactosaemia: evidence for a direct oxidative pathway. Am J Med 44: 340–347.

    Google Scholar 

  • Segal S, Blair A, Roth H (1965) The metabolism of 14Cgalactose by patients with congenital galactosaemia. Am J Med 38: 62–70.

    Google Scholar 

  • Segal S, Rogers S, Holtzapple PG (1971) Liver galactose-1-phosphate uridyltransferase: activity in normal and galactosemic subjects. J Clin Invest 50: 500–506.

    Google Scholar 

  • Tedesco TA, Miller KL (1979) Galactosaemia: alterations in sulfate metabolism secondary to galactose-1-phosphate uridyltransferase deficiency. Science 205: 1395–1397.

    Google Scholar 

  • Wadekind JE, Frey DA, Rayment I (1995) Three dimensional structure of galactose-1-phosphate uridyltransferase from Escherichia coli at 1.8 Å resolution. Biochemistry 34: 11049–11061.

    Google Scholar 

  • Waggoner DD, Buist NRM, Donnell G (1990) Long-term prognosis in galactosaemia: results of a survey of 350 cases. J Inher Metab Dis 13: 802–818.

    Google Scholar 

  • Wehrli S, Palmieri MJ, Berry GT, Kirkman HN, Segal S (1992) 31P-NMR analysis of red blood cell UDPglucose and UDPgalactose: comparison with HPLC and enzymatic methods. Anal Biochem 201(1): 105–110.

    Google Scholar 

  • Wehrli S, Berry GT, Palmieri MJ, Mazur A, Elsas LJ, Segal S (1997) Urinary galactonate in patients with galactosemia: quantitation by NMR spectroscopy. Pediatr Res 42: 855–861.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Segal, S. Komrower Lecture: Galactosaemia today: The enigma and the challenge. J Inherit Metab Dis 21, 455–471 (1998). https://doi.org/10.1023/A:1005402618384

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1005402618384

Keywords

Navigation