Galactose-1-Phosphate Uridyltransferase (GALT), Blood
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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 occur. 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 approximately 1 in 30,000, although literature reports range from 1 in 10,000 to 1 in 60,000 live births.
Galactose-1-phosphate (Gal-1-P) accumulates in the erythrocytes of patients with galactosemia. The quantitative measurement of Gal-1-P is useful for monitoring compliance with dietary therapy. Gal-1-P is thought to be the causative factor for development of liver disease in these patients and, because of this, patients should maintain low levels and be monitored on a regular basis.
Duarte-variant galactosemia (compound heterozygosity for the Duarte mutation, N314D, and a classic mutation) is generally associated with higher levels of enzyme activity (5%-20%) than classic galactosemia (<5%); however, this may be indistinguishable by newborn screening assays. Typically, individuals with Duarte-variant galactosemia have a milder phenotype, but are also often treated with a low galactose diet during infancy. The LA variant, which consists of N314D and a second mutation, L218L, is associated with higher levels of GALT enzyme activity than the Duarte-variant allele.
Newborn screening, which identifies potentially affected individuals by measuring total galactose (galactose and Gal-1-P) and/or determining the activity of the GALT enzyme, varies from state to state. The diagnosis of galactosemia is established by follow-up quantitative measurement of GALT enzyme activity. If enzyme levels are indicative of carrier or affected status, molecular testing for common GALT mutations may be performed. If 1 or both disease-causing mutations are not detected by targeted mutation analysis and biochemical testing has confirmed the diagnosis of galactosemia, sequencing of the GALT gene is available to identify private mutations.
Several disease-causing mutations are common in patients with classic galactosemia (G/G genotype). The most frequently observed is the Q188R classic mutation. This mutation accounts for 60% to 70% of classical galactosemia alleles. The S135L mutation is the most frequently observed mutation in African Americans and accounts for approximately 50% of the mutant alleles in this population. The K285N mutation is common in those of eastern European descent and accounts for 25% to 40% of the alleles in this population. The L195P mutation is observed in 5% to 7% of classical galactosemia. The Duarte mutation (N314D) is observed in 5% of the general US population.
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.
Diagnosis of galactose-1-phosphate uridyltransferase deficiency, the most common cause of galactosemia
Confirmation of abnormal state newborn screening results
An interpretive report will be provided.
If elevated galactose levels remain unexplainable by either a defect in galactose-1-phosphate uridyltransferase or galactokinase, a specimen can be sent, upon request, to an external laboratory to rule out a defect in galactose-4-epimerase.
See Galactosemia Testing Algorithm in Special Instructions for additional information. For galactokinase deficiency, see GALK / Galactokinase, Blood.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This assay is not useful for monitoring dietary compliance, see GAL1P / Galactose-1-Phosphate (Gal-1-P), Erythrocytes. This assay will not detect galactokinase deficiency or uridine diphosphate galactose 4-epimerase deficiency.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
> or =18.5 U/g of hemoglobin
Clinical References Provides recommendations for further in-depth reading of a clinical nature
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 Basis of Inherited Disease. Vol. 1. Eighth edition. Edited by CR Scriver, AL Beadut. New York, McGraw-Hill Book Company, 2001, pp 1553-1587