Test Catalog

Test Id : GCT

Galactosemia Reflex, Blood

Useful For
Suggests clinical disorders or settings where the test may be helpful

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

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

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. If quantitative GALT enzyme value is less than 24.5 nmol/h/mg of hemoglobin, full gene sequencing of the GALT gene is performed.

Reflex Tests
Lists tests that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial tests.

Test Id Reporting Name Available Separately Always Performed
FIBR Fibroblast Culture Yes No
CRYOB Cryopreserve for Biochem Studies No No
GALZ Galactosemia, Full Gene Analysis Yes No

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

Testing begins with galactose-1-phosphate uridyltransferase (GALT) enzyme analysis. If GALT activity is greater than or equal to 24.5 nmol/h/mg of hemoglobin, testing is complete. No molecular test will be performed. If GALT activity is less than 24.5 nmol/h/mg of hemoglobin, galactosemia full gene sequencing will be performed at an additional charge.

 

For more information see Galactosemia Testing Algorithm

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

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

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Galactosemia Reflex, B

Aliases
Lists additional common names for a test, as an aid in searching

Galactosemia Carrier Testing

Galactosemia Confirmation Test

Galactosemia Gene Analysis

GALT DNA

Galactosemia

Galactose-1-Phosphate Uridyltransferase (GALT)

Galactosemia Enzyme

Galactosemia Diagnostic Testing

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

Testing begins with galactose-1-phosphate uridyltransferase (GALT) enzyme analysis. If GALT activity is greater than or equal to 24.5 nmol/h/mg of hemoglobin, testing is complete. No molecular test will be performed. If GALT activity is less than 24.5 nmol/h/mg of hemoglobin, galactosemia full gene sequencing will be performed at an additional charge.

 

For more information see Galactosemia Testing Algorithm

Specimen Type
Describes the specimen type validated for testing

Whole Blood EDTA

Ordering Guidance

This test is appropriate for the diagnosis of and routine carrier screening for galactose-1-phosphate uridyltransferase (GALT) deficiency.

 

This assay is not appropriate for monitoring dietary compliance. For dietary monitoring, order GAL1P / Galactose-1-Phosphate, Erythrocytes.

Necessary Information

Patient's age is required.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Multiple whole blood tests for galactosemia can be performed on one specimen. Prioritize order of testing when submitting specimens. See Galactosemia-Related Test List for a list of tests that can be ordered together.

 

Container/Tube:

Preferred: Lavender top (EDTA)

Acceptable: Green top (sodium heparin) or yellow top (ACD)

Specimen Volume: 5 mL

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Forms

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. If not ordering electronically, complete, print, and send an Inborn Errors of Metabolism Test Request (T798) with the specimen.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

2 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis Reject

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

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

Useful For
Suggests clinical disorders or settings where the test may be helpful

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

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

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. If quantitative GALT enzyme value is less than 24.5 nmol/h/mg of hemoglobin, full gene sequencing of the GALT gene is performed.

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

Testing begins with galactose-1-phosphate uridyltransferase (GALT) enzyme analysis. If GALT activity is greater than or equal to 24.5 nmol/h/mg of hemoglobin, testing is complete. No molecular test will be performed. If GALT activity is less than 24.5 nmol/h/mg of hemoglobin, galactosemia full gene sequencing will be performed at an additional charge.

 

For more information see Galactosemia Testing Algorithm

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 any 1 of the 4 enzymes catalyzing the conversion of galactose to glucose: galactose-1-phosphate uridyltransferase (GALT), galactokinase (GALK), uridine diphosphate galactose-4-epimerase (GALE), and galactose mutarotase (GALM). 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.

 

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. Female patients 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 variant, N314D, and a classic variant) is generally associated with higher levels of enzyme activity (5%-20%) than classic galactosemia (<5%); however, this may be indistinguishable by newborn screening assays. Previously, it was unknown whether children with Duarte-variant galactosemia were at an increased risk for adverse developmental outcomes due to milk exposure so were often treated with a low galactose diet during infancy. More recently however, the outcomes data suggest a lack of evidence for developmental complications due to milk exposure, therefore treatment recommendations remain controversial. The Los Angeles variant, which consists of N314D and a second genetic variant, 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 level is less than 24.5 nmol/h/mg of hemoglobin, sequencing of the GALT gene is performed.

 

For more information see Galactosemia Testing Algorithm.

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 =24.5 nmol/h/mg of hemoglobin

Interpretation
Provides information to assist in interpretation of the test results

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.

 

In any specimen where enzyme activity is less than 24.5 nmol/h/mg of hemoglobin GALT full gene sequencing will be performed. For testing algorithm and more information, see Galactosemia Testing Algorithm.

 

The GALT gene maps to chromosome 9p13. Several disease-causing variants are common in patients with classic galactosemia (G/G genotype). The most frequently observed is the Q188R classic variant. This alteration accounts for 60% to 70% of classic galactosemia alleles. The S135L variant is the most frequently observed in African Americans and accounts for approximately 50% of the altered alleles in this population. The K285N variant is common in those of eastern European descent and accounts for 25% to 40% of the alleles in this population. The L195P variant is observed in 5% to 7% of classical galactosemia. The 5-kilobase deletion is common in individuals of Ashkenazi Jewish descent. The Duarte variant (N314D and -119_-116delGTCA) is observed in 5% of the general US population.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

This assay will not reliably detect deletions/insertions (delins) of 40 or more base pairs (bp), including Alu insertions, long interspersed elements (LINES), and short interspersed elements (SINES). The bioinformatics software pipeline is verified to detect 95% of deletions up to 75 bp and insertions up to 47 bp.

 

Additionally, low level mosaic variants may not be detected.

 

This test is not designed to differentiate between somatic and germline variants. If there is a possibility that any detected variant is somatic, additional testing may be necessary to clarify the significance of results.

 

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in the 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
Recommendations for in-depth reading of a clinical nature

1. Berry GT: Classic galactosemia and clinical variant galactosemia. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2000. Updated March 11, 2021. Accessed April 12, 2022. Available at www.ncbi.nlm.nih.gov/books/NBK1518/

2. Walter JH, Fridovich-Keil JL: Galactosemia. In: Valle D, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA. eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill; 2019 Accessed April 12, 2022. Available at https://ommbid.mhmedical.com/content.aspx?bookid=2709&sectionid=%20225081023

3. Carlock G, Fischer ST, Lynch ME, et al: Developmental outcomes in Duarte galactosemia. Pediatrics. 2019 Jan;143(1):e20182516. doi:10.1542/peds.2018-2516

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

Galactose-1-Phosphate Uridyltransferase Enzyme Analysis:

An aqueous mixture containing water, 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.

 

After incubation the reaction is quenched, extracted, and centrifuged. The top layer is then transferred to a 96-well plate, and then injected onto a liquid chromatography-tandem mass spectrometry (LC-MS/MS). The ratio of the extracted peak area of (13)C2 labeled UDP-galactose to its internal standard UDP-N-acetylglucosamine as determined by LC-MS/MS 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)

 

GALT Full Gene Sequencing:

Next-generation sequencing (NGS) and/or Sanger sequencing is performed to test for the presence of variants in coding regions and intron/exon boundaries of the GALT gene. NGS and/or a polymerase chain reaction (PCR)-based quantitative method is performed to test for the presence of deletions and duplications in the GALT gene.

 

There may be regions of GALT that cannot be effectively amplified for sequencing or deletion and duplication analysis because of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. Confirmation of select reportable variants may be performed by alternate methodologies based on internal laboratory criteria.

 

PCR-based methods and/or Sanger sequencing is used to confirm variants detected by NGS when appropriate.(Unpublished Mayo method)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday, Wednesday, Friday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

4 to 5 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

2 months

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

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 US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

82775

81406 (if appropriate)

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
GCT Galactosemia Reflex, B 24082-0
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
8333 Gal-1-P Uridyltransferase, RBC 24082-0
2296 Interpretation (GALT) 59462-2
58115 Reviewed By 18771-6

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports