Galactosemia Gene Analysis (6-Mutation Panel)
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Second-tier test for confirming a diagnosis of galactosemia (indicated by enzymatic testing or newborn screening)
Carrier testing family members of an affected individual of known genotype (has mutations included in the panel)
Resolution of Duarte variant and LA variant genotypes
Genetics Test Information Provides information that may help with selection of the correct test or proper submission of the test request
GALT (galactose-1-phosphate uridyltransferase) enzyme analysis (GALT / Galactose-1-Phosphate Uridyltransferase (GALT), Blood) is recommended prior to gene analysis. See GCT / Galactosemia Reflex, Blood for comprehensive diagnostic and carrier testing.
Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.
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
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 Gene Analysis
Specimen Type Describes the specimen type needed for testing
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.
Specimen must arrive within 96 hours of draw.
Preferred: Lavender top (EDTA) or yellow top (ACD)
Acceptable: Any anticoagulant
Specimen Volume: 3 mL
1. Invert several times to mix blood.
2. Send specimen in original tube.
1. Molecular Genetics-Biochemical Disorders Patient Information Sheet (Supply T527) in Special Instructions
2. 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.
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.
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Classical galactosemia is an autosomal recessive disorder of galactose metabolism caused by mutations in the galactose-1-phosphate uridyltransferase (GALT) gene. The complete or near complete deficiency of the GALT enzyme is life threatening. If left untreated, complications include liver failure, sepsis, mental retardation, and death. Galactosemia is treated by a galactose-free diet, which allows for rapid recovery from the acute symptoms and a generally good prognosis. Despite adequate treatment from an early age, children 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. The prevalence of classic galactosemia is approximately 1 in 30,000.
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 change, 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 galactose-1-phosphate) 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.
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 Duarte mutation (N314D) is observed in 5% of the general United States population.
The above mutations, in addition to the LA variant, are included in GAL6 / Galactosemia Gene Analysis (6-Mutation Panel) and in GCT / Galactosemia Reflex, Blood. See Galactosemia Testing Algorithm in Special Instructions for additional information. Refer to Galactosemia: Current Testing Strategy and Aids for Test Selection, Mayo Medical Laboratories Communique 2005 May;30(5) for more information regarding diagnostic strategy.
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.
An interpretive report will be provided.
An interpretative report will be provided.
Results should be interpreted in the context of biochemical results.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
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.
Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.
In rare cases, DNA alterations of undetermined significance may be identified.
A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.
Many disorders may present with symptoms similar to those associated with galactosemia. Therefore, biochemical testing is recommended 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. Kaye CI, Committee on Genetics, Accurso F, et al: Newborn screening fact sheets. Pediatrics 2006 Sep;118(3):e934-963
3. 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
Method Description Describes how the test is performed and provides a method-specific reference
Direct Mutation Analysis: A PCR-based assay utilizing fluorescence resonance energy transfer (FRET) probes, melt-curve analysis, and LightCycler technology is used to examine the GALT gene for the presence of the 6 mutations (see Clinical Information).(Wittwer CT, Herrmann MG, Gundry CN, Elenitoba-Johnson KS: Real-time multiplex PCR assays. Methods 2001 Dec;25:430-432)
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.
Tuesday; 10 a.m.
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
Whole Blood: 2 weeks (if available) Extracted DNA: 3 months
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.
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|
|22584||Reason For Referral||42349-1|