Classical galactosaemia revisited
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Classical galactosaemia (McKusick 230400) is an: autosomal recessive disorder of galactose metabolism, caused by a deficiency of the enzyme galactose-1-phosphate uridyltransferase (GALT; EC 2.7.712). Most patients present in the neonatal period, after ingestion of galactose, with jaundice, hepatosplenomegaly, hepatocellular insufficiency, food intolerance, hypoglycaemia, renal tubular dysfunction, muscle hypotonia, sepsis and cataract. The gold standard for diagnosis of classical galactosaemia is measurement of GALT activity in erythrocytes. Gas-chromatographic determination of urinary sugars and sugar alcohols demonstrates elevated concentrations of galactose and galactitol. The only therapy for patients with classical galactosaemia is a galactose-restricted diet, and initially all galactose must be removed from the diet as soon as the diagnosis is suspected. After the neonatal period, a lactose-free diet is advised in most countries, without restriction of galactose-containing fruit and vegetables. In spite of the strict diet, long-term complications such as retarded mental development, verbal dyspraxia, motor abnormalities and hypergonadotrophic hypogonadism are frequently seen in patients with classical galactosaemia. It has been suggested that these complications may result from endogenous galactose synthesis or from abnormal galactosylation. Novel therapeutic strategies, aiming at the prevention of galactose 1-phosphate production, should be developed. In the meantime, the follow-up protocol for patients with GALT deficiency should focus on early detection, evaluation and, if possible, early intervention in problems of motor, speech and cognitive development.
endogenous galactose synthesis
Health Related Quality of Life
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- Cuatrecasas P, Segal S (1996) Galactose conversion to d-xylulose. An alternative route of galactose metabolism. Science 153(735): 549–551.Google Scholar
- Holton JB, Walter JH, Tyfield LA (2001) Galactosemia. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds; Childs B, Kinzler KW, Vogelstein B, assoc eds. The Metabolic and Molecular Basis of Inherited Disease, 8th edn. New York: McGraw-Hill, 1553–1583.Google Scholar
- Hutchesson ACJ, Murdoch-Davies C, Green A, et al (1999) Biochemical monitoring of treatment for galactosemia: biological variability in metabolite concentrations. J Inherit Metab Dis 22: 138–148.Google Scholar
- Lebea PJ, Pretorius PJ (2005) The molecular relationship between deficient UDP-galactose uridyl transferase (GALT) and ceramide galactosyltransferase (CGT) enzyme function: a possible cause for poor long-term prognosis in classic galactosemia. Med Hypotheses 65(6): 1051–1057.PubMedCrossRefGoogle Scholar
- Levy HL, Driscoll SG, Porensky RS, Wender DF (1994) Ovarian failure in galactosemia. N Engl J Med 310: 50.Google Scholar
- Nelson MD, Wolff JA, Cross CA, Donnell GN, Kaufman FR (1982) Galactosemia: evaluation with MR imaging. Radiology 184: 255–261.Google Scholar
- Thompson SM, Netting MJ, Jerath S, Wiley V (2003) Effect of a less restricted diet in galactosemia. J Inherit Metab Dis 26(Supplement 2): 214.Google Scholar
- Tyfield L, Carmichael D. The galactose-1-phosphate uridyltransferase mutation analysis database home page. (GALTdB) at http://www.ich.bris.ac.uk/galtdb/.