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Galactosemia: Clinical features and diagnosis

V Reid Sutton, MD
Section Editors
Sihoun Hahn, MD, PhD
Elizabeth B Rand, MD
Deputy Editor
Elizabeth TePas, MD, MS


Galactose is a sugar found primarily in human and bovine milk and milk products as part of the disaccharide lactose. Lactose is hydrolyzed to glucose and galactose by the intestinal enzyme lactase. The galactose then is converted to glucose for use as an energy source (figure 1). Free galactose also is present in some fruits and vegetables, such as tomatoes, Brussels sprouts, bananas, and apples. Altered metabolism of galactose caused by deficient enzyme activity or impaired liver function results in elevated blood galactose concentration and the condition known as galactosemia.

The clinical features and diagnosis of galactosemia will be discussed here. The management of galactosemia is discussed separately. (See "Galactosemia: Management and outcome".)


Classic galactosemia occurs in approximately 1 of 60,000 livebirths. However, the reported incidence of galactosemia varies geographically from 1 in 30,000 to 40,000 in Europe [1] to one in one million in Japan [2]. The estimated incidence in the United States is 1 in 53,000 [3].


Galactosemia can result from deficiencies of three different enzymes (figure 1), each with a distinct phenotype. Impairment of galactose metabolism caused by abnormal liver function also may result in increased galactose concentrations. Impaired galactose metabolism appears to alter gene expression through epigenetic mechanisms, which may contribute to cognitive and other problems [4].

Galactose-1-phosphate uridyl transferase (GALT) deficiency – The most common and severe form of galactosemia is caused by deficiency of GALT, the enzyme that converts galactose-1-phosphate (galactose-1-P) to uridine diphosphate galactose (UDPgalactose) (figure 1).


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Literature review current through: Sep 2016. | This topic last updated: Dec 16, 2015.
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  1. Murphy M, McHugh B, Tighe O, et al. Genetic basis of transferase-deficient galactosaemia in Ireland and the population history of the Irish Travellers. Eur J Hum Genet 1999; 7:549.
  2. Hirokawa H, Okano Y, Asada M, et al. Molecular basis for phenotypic heterogeneity in galactosaemia: prediction of clinical phenotype from genotype in Japanese patients. Eur J Hum Genet 1999; 7:757.
  3. National Newborn Screening and Genetics Resource Center; 2002 Newborn Screening and Genetic Testing Symposium.
  4. Coman DJ, Murray DW, Byrne JC, et al. Galactosemia, a single gene disorder with epigenetic consequences. Pediatr Res 2010; 67:286.
  6. Kelley RI, Segal S. Evaluation of reduced activity galactose-1-phosphate uridyl transferase by combined radioisotopic assay and high-resolution isoelectric focusing. J Lab Clin Med 1989; 114:152.
  7. Ficicioglu C, Thomas N, Yager C, et al. Duarte (DG) galactosemia: a pilot study of biochemical and neurodevelopmental assessment in children detected by newborn screening. Mol Genet Metab 2008; 95:206.
  8. Walter JH, Fridovich-Keil JL. Galactosemia. In: The Online Metabolic and Molecular Bases of Inherited Disease, Valle D, Beaudet AL, Vogelstein B, et al (Eds), 2014. http://ommbid.mhmedical.com/book.aspx?bookid=971 (Accessed on December 09, 2015).
  9. Leslie ND, Immerman EB, Flach JE, et al. The human galactose-1-phosphate uridyltransferase gene. Genomics 1992; 14:474.
  10. Shield JP, Wadsworth EJ, MacDonald A, et al. The relationship of genotype to cognitive outcome in galactosaemia. Arch Dis Child 2000; 83:248.
  11. Cleary MA, Heptinstall LE, Wraith JE, Walter JH. Galactosaemia: relationship of IQ to biochemical control and genotype. J Inherit Metab Dis 1995; 18:151.
  12. Kaufman FR, Reichardt JK, Ng WG, et al. Correlation of cognitive, neurologic, and ovarian outcome with the Q188R mutation of the galactose-1-phosphate uridyltransferase gene. J Pediatr 1994; 125:225.
  13. Ridel KR, Leslie ND, Gilbert DL. An updated review of the long-term neurological effects of galactosemia. Pediatr Neurol 2005; 33:153.
  14. Waggoner DD, Buist NR, Donnell GN. Long-term prognosis in galactosaemia: results of a survey of 350 cases. J Inherit Metab Dis 1990; 13:802.
  15. Segal S. Komrower Lecture. Galactosaemia today: the enigma and the challenge. J Inherit Metab Dis 1998; 21:455.
  16. Walter JH, Collins JE, Leonard JV. Recommendations for the management of galactosaemia. UK Galactosaemia Steering Group. Arch Dis Child 1999; 80:93.
  17. Gitzelman R. Hereditary galactokinase deficiency: a newly recognized cause of juvenile cataracts. Pediatr Res 1967; 1:14.
  18. Litman N, Kanter AI, Finberg L. Galactokinase deficiency presenting as pseudotumor cerebri. J Pediatr 1975; 86:410.
  19. Walter JH, Roberts RE, Besley GT, et al. Generalised uridine diphosphate galactose-4-epimerase deficiency. Arch Dis Child 1999; 80:374.
  20. Openo KK, Schulz JM, Vargas CA, et al. Epimerase-deficiency galactosemia is not a binary condition. Am J Hum Genet 2006; 78:89.
  21. Jakobs C, Kleijer WJ, Allen J, Holton JB. Prenatal diagnosis of galactosemia. Eur J Pediatr 1995; 154:S33.
  22. Ono H, Mawatari H, Mizoguchi N, et al. Clinical features and outcome of eight infants with intrahepatic porto-venous shunts detected in neonatal screening for galactosaemia. Acta Paediatr 1998; 87:631.
  23. Müller D, Santer R, Krawinkel M, et al. Fanconi-Bickel syndrome presenting in neonatal screening for galactosaemia. J Inherit Metab Dis 1997; 20:607.
  24. Sakura N, Mizoguchi N, Ono H, et al. Congenital biliary atresia detected as a result of galactosemia screening by the Beutler method. Clin Chim Acta 2000; 298:175.