Galactose-1-Phosphate Uridyltransferase Deficiency (Galactosemia)

Updated: Nov 12, 2018
  • 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, 4, 5, 6] In the American literature, it was first described in a variant patient in 1935 by Mason and Turner, [7] while, in Europe, the toxicity associated with breast milk consumption was first noted in 1908 by Von Reuss. [8] Both patients probably had galactose-1-phosphate uridyltransferase (GALT) deficiency, which is the most common enzyme deficiency that causes hypergalactosemia. [7] Removing lactose largely eliminates the toxicity associated with newborn disease, but long-term complications routinely occur, as reported by Komrower and Lee in 1970 [9] and then delineated in a 1990 retrospective survey by Waggoner and associates [10] and Waisbren et al in 2012. [11]



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. [12]
  • 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

The incidence of galactosemia is approximately 1 case per 40,000-60,000 persons. [2]


Incidence widely varies (ie, 1 case in 70,000 people in the UK but 1 case in 16,476 people in Ireland [2, 3] ). The disorder is believed to be much less common in Asian persons.


Aside from the high mortality rate in newborns with Escherichia colisepsis, life expectancy has never been studied in patients with galactosemia. Most patients appear to reach adulthood following institution of a galactose-restricted diet. [1, 5, 13]


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

Variants are most notable among individuals of African ethnicity. African-Americans with galactosemia may have approximately 10% of enzyme activity in the liver but little or no activity in erythrocytes. [3, 4] 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 D-2 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. [14] 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 D-1 variant, has the same c.940 A>G (p.Asn314Asp) mutation as the Duarte variant but without the promoter region tetranucleotide GTCA deletion. [14] However, the Los Angeles variant has a different neutral polymorphism, delineated Leu218Leu. [15] This variant results in increased GALT activity and does not cause hypergalactosemia.

Dietary galactose restriction does not appear to be necessary or beneficial in patients with Duarte D-2 variant galactosemia. 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 D-2 variant. [16, 17]


Galactosemia equally affects males and females.


Galactosemia is most often diagnosed in infancy via newborn screening, because all states include galactosemia as part of their newborn screen. [5] Variant forms of galactosemia can present later.



Untreated severe classic galactosemia is a life-threatening disorder. [5] Fortunately, most states and developed countries screen for galactosemia in the newborn period, and affected infants are treated before they become very ill. [18]

Infants with galactosemia who are severely ill (eg, those with sepsis, coagulopathy, liver dysfunction) before treatment for galactosemia is initiated may develop permanent liver, brain, and/or eye damage (although cataracts are often completely reversible).

Most patients with severe galactosemia who do not receive treatment often do not survive the newborn period.

Even with appropriate dietary therapy, most patients have at least 1-2 long-term complications.

Almost all females with classic galactosemia present with hypergonadotropic hypogonadism/primary ovarian insufficiency (POI). [19]

Some patients with galactosemia may have cryptic gastrointestinal tract dysfunction. [20]


Patient Education

Dietary therapy requires both parental and patient education. Involve children in their dietary management as soon as appropriate.