Galactosemia Reflex, Blood
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
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 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 (GALT/8333 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 (GAL6/84366 Galactosemia Gene Analysis [6-Mutation Panel]) is performed to detect the 4 most frequently encountered classic galactosemia alleles (Q188R, S135L, K285N, and L195P) in addition to the N314D (Duarte) and L218L (Los Angeles) variants.
Reflex Tests Lists test(s) that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial test(s)
|Test ID||Reporting Name||Available Separately||Always Performed|
|GAL6||Galactosemia Gene Analysis||Yes||No|
Testing Algorithm Delineates situation(s) 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 is > or =18.5 U/g of hemoglobin, testing is complete. No molecular test will be performed. If GALT is <18.5 U/g of hemoglobin, GAL6/84366 Galactosemia Gene Analysis (6-Mutation Panel) will be performed at an additional charge.
See Galactosemia Testing Algorithm in Special Instructions.
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
GALT/8333: Ultraviolet, Kinetic
GAL6/84366: A real-time polymerase chain reaction (PCR)-based assay is utilized to examine DNA for 6 alterations: Q188R, S135L, L195P, K285N, N314D (Duarte), and L218L (Los Angeles).
(PCR is utilized pursuant to a license agreement with Roche Molecular Systems, Inc.)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Galactosemia Reflex, B
Galactosemia Carrier Testing
Galactosemia Confirmation Test
Galactosemia Enzyme (verify which test)
Galactosemia Gene Analysis
Galactose-1-Phosphate Uridyltransferase (GALT)
Galactosemia Confirmation Test
Galactosemia Enzyme (verify which test)
Galactosemia Gene Analysis
Galactose-1-Phosphate Uridyltransferase (GALT)
Specimen Type Describes the specimen type needed for testing
Whole Blood EDTA
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Container/Tube: Lavender top (EDTA)
Specimen Volume: 5 mL
Additional Information: Patient's age is required.
1. 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 (Supply T576) is available in Special Instructions.
2. If not ordering electronically, please submit the following forms with the specimen:
-Molecular Genetics Request Form (Supply T245)
-Biochemical Genetics Request Form (Supply T439)
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Mild OK; Gross reject
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
|Whole Blood EDTA||Refrigerated (preferred)||28 days|
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.
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
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 <18.5 U/g hemoglobin will be analyzed for the presence of the 4 mutations associated with classic galactosemia, as well as the 2 variants (Duarte and LA). See Galactosemia Reflex Algorithm in Special Instructions for testing algorithm and additional information.
This test detects 4 of the most frequently encountered classic galactosemia alleles (Q188R, S135L, K285N, and L195P), as well as the N314D Duarte and L218L LA variants. 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.
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 by galactosemics, see GAL1P/80337 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(s) 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 Provides recommendations for further in-depth reading of a clinical nature
1. Elsas LJ 2nd, Lai K: The molecular biology of galactosemia. Genet Med 1998 Nov-Dec;1(1):40-48
2. Novelli G, Reichardt JK: Molecular basis of disorders of human galactose metabolism: past, present, and future. Mol Genet Metab 2000 Sep-Oct;71(1-2):62-65
3. Walter JH, Collins JE, Leonard JV: Recommendations for the management of galactosemia. Arch Dis Child 1999 Jan;80(1):93-96
Method Description Describes how the test is performed and provides a method-specific reference
Galactose-1-phosphate uridyltransferase converts uridine diphosphoglucose (UDPG) to UDP-galactose. The amount of UDPG consumed is measured by oxidizing UDPG with concomitant generation of NADPH from NADP (UDPG-dehydrogenase), which is measured at 340 nm. (Beutler E, Baluda MC: Improved method for measuring galactose-1-phosphate uridyl transferase activity of erythrocytes. Clin Chim Acta 1966 March;13:369-379)
A real-time PCR-based assay using the LightCycler detects 6 alterations: Q188R, L195P, S135L, K285N, L218L, and N314D. (Dobrowolski SF, Banas RA, Suzow JG, et al: Analysis of common mutations in the galactose-1-phosphate uridyl transferase gene. J Mol Diagn 2003;5:42-47)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Varies; batching samples due to reagent shortage
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
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's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) 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 U.S. 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 Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
Galactose-1-Phosphate Uridyltransferase (GALT), Blood
Galactosemia Gene Analysis (6-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 Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
|Result ID||Reporting Name||LOINC Code|
|8333||Gal-1-P Uridyltransferase, RBC||24082-0|