Interpretive Handbook

Galactosemia is an autosomal recessive disorder that results from a deficiency of 1 of the 3 enzymes catalyzing the conversion of galactose to glucose: galactose-1-phosphate uridyltransferase (GALT), galactokinase (GALK), and uridine diphosphate galactose-4-epimerase (GALE). GALT deficiency is the most common cause of galactosemia and is often referred to as classic galactosemia. The complete or near-complete deficiency of GALT enzyme is life-threatening if left untreated. Complications in the neonatal period include failure to thrive, liver failure, sepsis, and death; even with survival, long-term intellectual disability can result. Galactosemia is treated by a galactose-restricted diet, which allows for rapid recovery from the acute symptoms and a generally good prognosis. Despite adequate treatment from an early age, individuals with galactosemia remain at increased risk for developmental delays, speech problems, and abnormalities of motor function. Females with galactosemia are at increased risk for premature ovarian failure. Based upon reports by newborn screening programs, the frequency of classic galactosemia in the United States is 1 in 30,000, although literature reports range from 1 in 10,000 to 1 in 60,000 live births.

A comparison of plasma and urine galactose and blood galactose-1-phosphate (Gal-1-P) levels may be useful in distinguishing between the 3 forms of galactosemia.

For more information regarding diagnostic strategy, refer to Galactosemia: Current Testing Strategy and Aids for Test Selection, Mayo Medical Laboratories Communique 2005 May;30(5).

See Galactosemia Testing Algorithm in Special Instructions for additional information.

Screening for galactosemia. Additional testing is required to investigate cause of abnormal results.

In patients with galactosemia, elevated galactose in plasma or urine may suggest ineffective dietary restriction or compliance; however, the concentration of galactose-1-phosphate in erythrocytes (GAL1P/80337 Galactose-1-Phosphate [Gal-1-P], Erythrocytes) is the most sensitive index of dietary control. Increased concentrations of galactose may also be suggestive of severe hepatitis, biliary atresia of the newborn, and, in rare cases, galactose intolerance.

If galactosemia is suspected, additional testing to identify the specific enzymatic defect is required. See Galactosemia Testing Algorithm in Special Instructions for follow-up of abnormal newborn screening results, comprehensive diagnostic testing, and carrier testing. See GALT/8333 Galactose-1-Phosphate Uridyltransferase (GALT), Blood for GALT testing and GALK/8628 Galactokinase, Blood for GALK testing. Uridine diphosphate galactose-4-epimerase (GALE) enzyme testing is not available at Mayo Medical Laboratories; upon request, specimens will be forwarded to an external laboratory. Results should be correlated with clinical presentation and confirmed by specific enzyme or molecular analysis.

The preferred test for monitoring dietary therapy is GAL1P/80337 Galactose-1-Phosphate (Gal-1-P), Erythrocytes.

1-7 days: <5.4 mg/dL

8-14 days: <3.6 mg/dL

>14 days: <2.0 mg/dL

1. Elsas LJ: Galactosemia. NCBI GeneReviews. Updated 2010, Oct 26. Available from www.ncbi.nlm.nih.gov/books/NBK1518

2. Holton JB, Walter JH, Tyfield LA: Galactosemia. In The Metabolic and Molecular Bases of Inherited Disease. 8th edition. Edited by CR Scriver, AL Beaudet, D Valle, et al: New York, McGraw-Hill Book Company, 2001, pp 1553-1587

3. Shin YS: Galactose metabolites and disorders of galactose metabolism. In Techniques in Diagnostic Human Biochemical Genetics. Edited by FA Holmes. New York, Wiley-Liss, 1991, pp 267-283