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Galactose-1-Phosphate Uridyltransferase Deficiency (Galactosemia)

  • Author: Gerard T Berry, MD; Chief Editor: Maria Descartes, MD  more...
Updated: Feb 20, 2015


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.

Contributor Information and Disclosures

Gerard T Berry, MD Harvey Levy Chair in Metabolism, Director, Metabolism Program, Division of Genetics, Boston Children's Hospital; Professor of Pediatrics, Harvard Medical School

Gerard T Berry, MD is a member of the following medical societies: American College of Medical Genetics and Genomics, American Diabetes Association, Sigma Xi, Society for Pediatric Research, American Society of Human Genetics, Federation of American Societies for Experimental Biology, Pediatric Endocrine Society

Disclosure: Nothing to disclose.


George A Anadiotis, DO Consulting Staff, Department of Pediatric Rehabilitation and Development, Division of Clinical and Biochemical Genetics, Emmanuel Children's Hospital

George A Anadiotis, DO is a member of the following medical societies: American Medical Association, American Society of Human Genetics

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Eric T Rush, MD, FAAP, FACMG Clinical Geneticist, Munroe-Meyer Institute for Genetics and Rehabilitation; Assistant Professor of Pediatrics and Internal Medicine, University of Nebraska Medical Center

Eric T Rush, MD, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics, American College of Physicians, Nebraska Medical Association

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Alexion Pharmaceuticals<br/>Honoraria for: Alexion Pharmaceuticals and Biomarin Pharmaceuticals.

Chief Editor

Maria Descartes, MD Professor, Department of Human Genetics and Department of Pediatrics, University of Alabama at Birmingham School of Medicine

Maria Descartes, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics, American Medical Association, American Society of Human Genetics, Society for Inherited Metabolic Disorders, International Skeletal Dysplasia Society, Southeastern Regional Genetics Group

Disclosure: Nothing to disclose.

Additional Contributors

Robert D Steiner, MD Chief Medical Officer, Acer Therapeutics; Clinical Professor, University of Wisconsin School of Medicine and Public Health

Robert D Steiner, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American College of Medical Genetics and Genomics, American Society of Human Genetics, Society for Inherited Metabolic Disorders, Society for Pediatric Research, Society for the Study of Inborn Errors of Metabolism

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Acer Therapeutics; Retrophin; Raptor Pharma; Veritas Genetics; Censa Pharma<br/>Received income in an amount equal to or greater than $250 from: Acer Therapeutics; Retrophin; Raptor Pharma; Censa Pharma.

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