Test Catalog

Test Id : GALMP

Galactosemia, GALT Gene, Variant Panel, Varies

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

Second-tier test for confirming a diagnosis of galactosemia as indicated by enzymatic testing or newborn screening

 

Carrier testing family members of an affected individual of known genotype (has variants included in the panel)

 

Resolution of Duarte variant and Los Angeles (LA) variant genotypes

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

This targeted genotyping panel is for 24 variants in the GALT gene. For details regarding the specific variants for this test, see the Targeted Variants Table in Clinical Information.

Highlights

A targeted genotyping array is utilized to detect 24 genetic targets associated with galactosemia for the purpose of diagnostic testing or carrier screening.

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

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

Targeted Genotyping Array

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 Mutation Panel

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

Duarte

Galactosemia

GALT

GALMP

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

For more information see Galactosemia Testing Algorithm

Specimen Type
Describes the specimen type validated for testing

Varies

Ordering Guidance

The recommended as a first-tier test is galactose-1-phosphate uridyltransferase enzyme analysis; order GALT / Galactose-1-Phosphate Uridyltransferase, Blood.

 

This genetic variant panel is recommended for individuals with a GALT enzyme value less than 24.5 nmol/h/mg of hemoglobin.

Shipping Instructions

Specimen preferred to arrive within 96 hours of collection.

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.

 

Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.

 

Specimen Type: Whole blood

Container/Tube:

Preferred: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send whole blood specimen in original tube. Do not aliquot.

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. Molecular Genetics: Biochemical Disorders Patient Information (T527)

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

1 mL

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

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

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
Varies Ambient (preferred)
Frozen
Refrigerated

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

Second-tier test for confirming a diagnosis of galactosemia as indicated by enzymatic testing or newborn screening

 

Carrier testing family members of an affected individual of known genotype (has variants included in the panel)

 

Resolution of Duarte variant and Los Angeles (LA) variant genotypes

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

This targeted genotyping panel is for 24 variants in the GALT gene. For details regarding the specific variants for this test, see the Targeted Variants Table in Clinical Information.

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

For more information see Galactosemia Testing Algorithm

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 genetic variants 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, intellectual disability, 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. Women 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 variant, N314D and -119_-116delGTCA in cis [on the same chromosome], and a classic variant in trans [on the opposite chromosome]) 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 (LA) variant, which consists of N314D without the presence of -119_-116delGTCA, is associated with normal levels of GALT enzyme activity.

 

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 variants may be performed. If one or both disease-causing variants are not detected by targeted variant analysis and biochemical testing has confirmed the diagnosis of galactosemia, sequencing of the GALT gene is available to identify private variants.

 

The GALT gene maps to 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 variant accounts for 60% to 70% of classical galactosemia alleles. The S135L variant is the most frequently observed variant 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 United States population. The rest of the variants detected by this method are all uncommon but known to be recurrent in the general population.

 

These variants, in addition to the LA variant, are included in this test and in GCT / Galactosemia Reflex, Blood. For more information see Galactosemia Testing Algorithm.

 

Table. Targeted Variants

Associated phenotype

Gene (transcript)

Variants

Galactosemia

GALT (NM_000155)

c.-119_-116del*, c.136_140del, c.221T>C*, c.253-2A>G*, c.292G>A*, c.404C>T*, c.413C>T*, c.425T>A*, c.443G>A*, c.505C>A, c.512T>C*, c.563A>G*, c.584T>C*, c.607G>A*, c.626A>G*, c.855G>T*, c.940A>G*, c.958G>A*, c.997C>G*, c.997C>T*, c.1018G>T, c.1030C>A*, c.1138T>C*
Deletion analysis of exon 1-11

 

*Previously detected in a known positive sample

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.

Interpretation
Provides information to assist in interpretation of the test results

An interpretative report will be provided.

 

Results should be interpreted in the context of biochemical results.

 

If results of the galactose-1-phosphate uridyltransferase enzyme analysis and this test are discordant, then consider GALZ / Galactosemia, GALT Gene, Full Gene Analysis, Varies.

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 known disease-associated variants that cause galactosemia. Therefore, the absence of a detectable variant does not rule out the possibility that an individual is a carrier of or affected with this disease.

 

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.

 

A negative result does not eliminate the risk of carrier status for any of the included conditions, due to the possibility that the patient carries a variant that is not interrogated with this assay or the rare chance of a false-negative result for a tested variant. For tested variants, the negative predictive value of this screen is greater than 98%. The patient's residual risk to be a carrier after a negative screen is dependent on ethnic background and family history.

 

A positive control was not available for all variants targeted on this panel. For more information regarding availability of a positive control for each variant see the Table (Targeted Variants) in Clinical Information.. The negative predictive value of these targets is unknown.

 

Rare variants (ie, 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.

 

All detected variants are evaluated according to American College of Medical Genetics and Genomics recommendations.(1) This assay was designed to specifically target known pathogenic or likely pathogenic variants. In rare cases, DNA variants of undetermined significance may be identified. The laboratory encourages health care providers to contact the laboratory at any time to learn how the status of a particular variant may have changed over time.

 

Multiple in-silico evaluation tools may have been used to assist in the interpretation of these results. Of note, the sensitivity and specificity of these tools for the determination of pathogenicity is currently unvalidated.

 

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

 

Bone Marrow transplants from allogenic donors will interfere with testing. Call Mayo Clinic Laboratories for instructions for testing patients who have received a bone marrow transplant.

 

An online research opportunity called GenomeConnect (genomeconnect.org), a project of ClinGen, is available for the recipient of this genetic test. This patient registry collects deidentified genetic and health information to advance the knowledge of genetic variants. Mayo Clinic is a collaborator of ClinGen. This may not be applicable for all tests.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015 May;17(5):405-424. doi: 10.1038/gim.2015.30

2. Elsas LJ 2nd, Lai K: The molecular biology of galactosemia. Genet Med. 1998 Nov-Dec;1(1):40-48. doi: 10.1097/00125817-199811000-00009

3. Kaye CI, Committee on Genetics, Accurso F, et al: Newborn screening fact sheets. Pediatrics. 2006 Sep;118(3):e934-e963. doi: 10.1542/peds.2006-1783

4. 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. doi: 10.1006/mgme.2000.3073

5. Welling L, Bernstein LE, Berry GT, et al: International clinical guideline for the management of classical galactosemia: diagnosis, treatment, and follow-up. J Inherit Metab Dis. 2017 Mar;40(2):171-176. doi: 10.1007/s10545-016-9990-5

6. 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

The targeted genotyping assay utilizing the ThermoFisher GeneTitan platform is used to detect 24 targets in the GALT gene. Confirmatory testing of homozygous results is performed as reflex tests when appropriate. For details regarding the targeted pathogenic variants identified by this test, see the Targeted Variants table in Clinical Information.

 

Multiplex ligation-dependent probe amplification, polymerase chain reaction (PCR), relative quantitative PCR, and Sanger sequencing are used to confirm variants detected by array 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.

Thursday, Sunday

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.

7 to 21 days

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
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.

81401

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
GALMP Galactosemia Mutation Panel 42318-6
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.
606344 Result Summary 50397-9
606345 Result 82939-0
606346 Interpretation 69047-9
606347 Additional Information 48767-8
606348 Method 85069-3
606349 Specimen 31208-2
606350 Source 31208-2
606351 Released 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

Test Update Resources

Change Type Effective Date
New Test 2022-08-23