Galactose-1-Phosphate Uridyltransferase Deficiency (Galactosemia)

Updated: Feb 20, 2015
  • Author: Gerard T Berry, MD; Chief Editor: Maria Descartes, MD  more...
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Hereditary galactosemia is among the most common carbohydrate metabolism disorders and can be a life-threatening illness during the newborn period. [1, 2, 3] First described in a variant patient in 1935 by Mason and Turner, galactose-1-phosphate uridyltransferase (GALT) deficiency is the most common enzyme deficiency that causes hypergalactosemia. [4] Removing lactose largely eliminates the toxicity associated with newborn disease, but long-term complications routinely occur, as reported by Komrower and Lee in 1970 [5] and then delineated in a 1990 retrospective survey by Waggoner and associates. [6]



Hypergalactosemia is associated with the following 3 enzyme deficiencies [1] :

  • Galactokinase converts galactose to galactose-1-phosphate and is not a common deficiency.

  • Uridine diphosphate (UDP) galactose-4-epimerase epimerizes UDP galactose to UDP glucose and is also uncommon.

  • GALT is responsible for hereditary galactosemia and is the most common deficiency. This enzyme catalyzes conversion of galactose-1-phosphate and UDP glucose to UDP galactose and glucose-1-phosphate. Individuals with GALT deficiency manifest abnormal galactose tolerance.




United States

Incidence is approximately 1 case per 40,000-60,000 persons. [3]


Incidence widely varies (ie, 1 case in 70,000 people in the UK but 1 case in 16,476 people in Ireland.) The disorder is thought to be much less common in Asians.


Aside from the high mortality rate in newborn infants with sepsis caused by Escherichia coli, life expectancy has never been studied in patients with galactosemia. Most patients appear to reach adulthood following institution of a galactose-restricted diet. [1, 7]


Galactosemia occurs in all races; however, galactosemia variants are based on the exact gene defect.

Variants are most notable among the black population. Affected individuals may have approximately 10% of enzyme activity in the liver but no activity in the erythrocytes. [2] The ability of an individual with the variant gene defect to tolerate ingestion of some milk may hinder diagnosis in states without newborn screening.

A likely benign variety is recognized, known as the Duarte variant, which is characterized by the simultaneous mutations c.940 A>G (p.Asn314Asp) and the tetranucleotide deletion GTCA in the promoter region of the gene . Neonates with this variant may or may not have positive (ie, abnormal) newborn screening test results, and most can tolerate normal diets. During infancy, but less so in childhood, these individuals may have elevated galactose metabolite levels.

A different variant, the Los Angeles variant, has the same c.940 A>G (p.Asn314Asp) mutation as the Duarte variant but without the promoter region tetranucleotide GTCA deletion. However, the Los Angeles variant has the different neutral polymorphism, delineated Leu218Leu. [8] This variant results in increased GALT activity and does not cause galactosemia.

Whether dietary galactose restriction is necessary or beneficial for patients with Duarte variant galactosemia is unknown. Many metabolic disease specialists take a conservative approach and recommend galactose restriction in the first year of life when milk intake is highest, but this restriction is based primarily on theoretical concerns of galactose toxicity in infants with the Duarte variant. [9]


Galactosemia equally affects males and females.


Galactosemia is most often diagnosed in infancy by newborn screening because all states include galactosemia as part of their newborn screen. Variant forms of galactosemia can present later.