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Test Code GCT Galactosemia Reflex, Blood

Performing Laboratory

Mayo Medical Laboratories in Rochester

Reporting Name

Galactosemia Reflex, B

Specimen Type

Whole Blood EDTA

Specimen Required


Preferred: Lavender top (EDTA)

Acceptable: Yellow top (ACD)

Specimen Volume: 5 mL

Additional Information: Patient's age is required.

Reject Due To


Mild OK; Gross reject







Specimen Stability Information

Specimen Type Temperature Time
Whole Blood EDTA Refrigerated (preferred) 28 days
  Ambient  14 days

Specimen Minimum Volume

2 mL

Day(s) and Time(s) Performed

Monday, Wednesday, Friday; 7 a.m. set up (specimen must arrive the day prior)

Specimen Retention Time

2 months

Analytic Time

4 days

Reference Values

≥24.5 nmol/h/mg of hemoglobin

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
GAL14 Galactosemia Gene Analysis Yes No

Useful For

Preferred test for diagnosis, carrier detection, and determination of genotype of galactose-1-phosphate uridyltransferase deficiency, the most common cause of galactosemia


Differentiating Duarte variant galactosemia from classic galactosemia


Confirming results of newborn screening programs

Testing Algorithm

Testing begins with galactose-1-phosphate uridyltransferase (GALT) enzyme analysis. If GALT is greater than or equal to 24.5 nmol/h/mg of hemoglobin, testing is complete. No molecular test will be performed. If GALT is less than 24.5 nmol/h/mg of hemoglobin, GAL14 / Galactosemia Gene Analysis (14-Mutation Panel) will be performed at an additional charge.


See Galactosemia Testing Algorithm in Special Instructions.

Method Name

Enzyme Reaction Followed by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information

Galactose-1-Phosphate Uridyltransferase (GALT), Blood



Galactosemia Gene Analysis (14-Mutation Panel)

81401-GALT (galactose-1-phosphate uridylyltransferase) (eg, galactosemia), common variants (eg, Q188R, S135L, K285N, T138M, L195P, Y209C, IVS2-2A->G, P171S, del5kb, N314D, L218L/N314D

LOINC Code Information

Test ID Test Order Name Order LOINC Value
GCT Galactosemia Reflex, B In Process


Result ID Test Result Name Result LOINC Value
8333 Gal-1-P Uridyltransferase, RBC 24082-0
2296 Interpretation (GALT) 59462-2
58115 Reviewed By No LOINC Needed

Clinical Information

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 Los Angeles 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 for galactosemia is performed in all 50 US states, though the method by which potentially affected individuals are detected varies from state to state and may include the measurement of total galactose (galactose and Gal-1-P) and/or determining the activity of the GALT enzyme. 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.


See Galactosemia Testing Algorithm in Special Instructions for additional information.


The laboratory provides an interpretation of the results, including galactose-1-phosphate uridyltransferase enzyme activity and genotype, if necessary. This interpretation provides an overview of the results and their significance, a correlation to available clinical information, elements of differential diagnosis, and recommendations for additional testing.


Any specimen where enzyme activity is less than 24.5 nmol/h/mg of hemoglobin will be analyzed for the presence of 14 mutations associated with classic galactosemia, as well as the 2 variants (Duarte and Los Angeles). See Galactosemia Reflex Algorithm in Special Instructions for testing algorithm and additional information.


The GALT gene maps to 9p13. 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 5-kb deletion is common in individuals of Ashkenazi Jewish descent. The Duarte mutation (N314D and -119_-116delGTCA) is observed in 5% of the general United States population. The rest of the mutations detected by this method (ie, D98N, S135L, T138M, M142K, F171S, Y209C, and Q344K) are all uncommon, but known to be recurrent in the general population.


A high proportion (20%) of patients with classic galactosemia have a private mutation. Since our assay does not investigate for the presence of private mutations, when GG, DG, or NG genotype is predicted by enzymatic studies and the current panel does not identify a mutation, molecular sequencing may be indicated.


This assay is not useful for monitoring dietary compliance, see GAL1P / Galactose-1-Phosphate (Gal-1-P), Erythrocytes.


This assay will not detect all of the mutations that cause galactosemia. Therefore, the absence of a detectable mutation does not rule out the possibility that an individual is a carrier of or affected with this disease.


Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.


Many disorders may present with symptoms similar to those associated with galactosemia. Therefore, biochemical testing is performed to establish the diagnosis of galactosemia prior to DNA analysis.

Clinical Reference

1. Berry GT: Classic Galactosemia and Clinical Variant Galactosemia. In GeneReviews. Edited by RA Pagon, MP Adam, HH Ardinger, et al. Retrieved 03/11/2015. Available at

2. Walter JH, Fridovich-Keil JL: Chapter 72: Galactosemia. In The Metabolic and Molecular Bases of Inherited Disease. Eighth edition. Edited by D Valle. AL Beaudet, B Vogelstein. New York, McGraw-Hill Book Company. Accessed 03/11/2015. Available at

Method Description

An aqueous mixture containing CLR H2O, uridine diphosphate (UDP)-glucose, (13)C(2)-labeled galactose-1-phosphate, and UDP-n-acetylglucosamine (internal standard) is added to hemolysate aliquot. The mixture is then vortexed briefly and incubated. The enzyme galactose-1-phosphate uridyltransferase (GALT) (EC will convert (13)C(2)-labeled galactose-1-phosphate to (13)C(2)-labeled UDP-galactose during the incubation.


Enzyme reaction:

(13)C(2)-galactose-1-phosphate + UDP-glucose -> (13)C(2)-UDP-galactose + glucose-1-phosphate


After incubation the reaction is quenched and extracted. The mixture is then centrifuged. The top acetonitrile extract layer is then transferred to a 96-well (Nunc, polypropylene) plate. Then extract is injected onto a liquid chromatography-tandem mass spectrometry (LC-MS/MS) API 3200 system for chromatographic separation and measurement of analytes. The MS/MS is operated in the multiple reaction monitoring (MRM) negative mode to follow the precursor to product species transitions for (13)C(2)-labeled UDP-galactose (567.0 to 322.9 m/z) and internal standard of UDP-n-acetylglucosamine (606.2 to 384.7 m/z). The ratio of the extracted peak area of (13)C(2)labeled UDP-galactose to its internal standard UDP-n-acetylglucosamine as determined by liquid chromatography-tandem mass spectrometry is used to calculate the concentration of product analyte in the sample. The concentration of the product is then normalized using the calculated hemoglobin concentration to determine the patient's enzyme level in nmol/h/mg of hemoglobin.(Unpublished Mayo method)


A PCR-based assay utilizing Sequenom Mass Array platform is used to test for the presence of the following 14 mutations in the GALT gene: -119_-116delGTCA, D98N, S135L, T138M, M142K, F171S, Q188R, L195P, Y209C, K285N, N314D, Q344K, c.253-2A>G, and 5 kb deletion.(Unpublished Mayo method)

Disease States

  • Galactosemia

Genetics Test Information

Preferred test to evaluate for possible diagnosis of galactosemia, routine carrier screening, and follow-up of abnormal newborn screening results. Comprehensive reflex test begins with quantitative galactose-1-phosphate uridyltransferase (GALT) enzyme analysis; GALT / Galactose-1-Phosphate Uridyltransferase (GALT), Blood. If quantitative GALT enzyme value is consistent with a diagnosis of or carrier status for galactosemia, DNA analysis of the GALT gene; GAL14 / Galactosemia Gene Analysis (14-Mutation Pane]) is performed to detect 14 galactosemia alleles : -119_-116delGTCA, D98N, S135L, T138M, M142K, F171S, Q188R, L195P, Y209C, K285N, N314D, Q344K, c.253-2A>G, and 5 kb deletion.


New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (T576) is available in Special Instructions.