Test Catalog

Test Id : G6PDB

Glucose-6-Phosphate Dehydrogenase (G6PD) Full Gene Sequencing, Varies

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

Genetic test for individuals at high risk for glucose-6-phosphate dehydrogenase (G6PD) deficiency

 

Aiding in the diagnosis of G6PD deficiency

 

Determining G6PD deficiency status in individuals with inconclusive or unexpected phenotyping results

 

Differentiation of heterozygous females with skewed X-inactivation from homozygous and compound heterozygous females

 

Definitive diagnosis of carrier status in females

 

Evaluation of neonates (particularly males) with unexplained jaundice

 

Identifying individuals at risk of drug-induced acute hemolytic anemia (AHA) related to G6PD deficiency

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

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a very common X-linked condition, impacting about 400 million people worldwide. Both males and females may be impacted due to how common G6PD deficiency is in the population.

 

Several medications, including rasburicase, methylene blue and dapsone, result in acute hemolytic anemia (AHA) when taken by individuals with G6PD deficiency.

 

FDA labeling and Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines recommend that G6PD testing be undertaken in high-risk populations before prescribing drugs known to cause AHA. Knowing a patient's genotype is generally sufficient to avoid contraindicated drugs, but follow-up with the phenotyping enzyme assay may be necessary to clarify results in some cases.

 

This test involves full gene sequencing of all exons and intron/exon boundaries of the G6PD gene. A comprehensive interpretation will be provided including congenital and pharmacogenomic implications of results. Testing should be considered before prescribing medication associated with hemolysis in individuals with G6PD deficiency.

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

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

Polymerase Chain Reaction (PCR) followed by DNA Sequence Analysis

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

G6PD Full Gene Sequencing

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

G6PD

Glucose-6-phosphate dehydrogenase deficiency.

Hemolytic anemia

Favism

hemolytic anemia

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

Specimen Type
Describes the specimen type validated for testing

Varies

Ordering Guidance

For initial or time-sensitive screening for glucose-6-phosphate dehydrogenase deficiency, order G6PD1 / Glucose 6-Phosphate Dehydrogenase Enzyme Activity, Blood.

Necessary Information

1. Patient's sex is required.

2. Include physician name and phone number with the specimen.

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

Submit only 1 of the following specimens:

 

Specimen Type: Whole blood

Container/Tube:

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

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube.

Specimen Stability Information: Ambient (preferred) 9 days/Refrigerated 30 days

 

Specimen Type: Saliva

Patient Preparation: Patient should not eat, drink, smoke, or chew gum 30 minutes prior to collection.

Supplies: Saliva Swab Collection Kit (T786)

Specimen Volume: 1 swab

Collection Instructions: Collect and send specimen per kit instructions.

Specimen Stability Information: Ambient 30 days

 

Specimen Type: Extracted DNA

Container/Tube: 2 mL screw top tube

Specimen Volume: 100 mcL (microliters)

Collection Instructions:

1. The preferred volume is 100 mcL at a concentration of 250 ng/mcL.

2. Include concentration and volume on tube.

Specimen Stability Information: Frozen (preferred)/Ambient/Refrigerated

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 in Special Instructions:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing (Spanish)  (T826)

2. If not ordering electronically, complete, print, and send 1 of the following forms with the specimen:

-Benign Hematology Test Request (T755)

-Therapeutics Test Request (T831)

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

Blood: 0.45 mL

Saliva: 1 swab

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 Varies (preferred)

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

Genetic test for individuals at high risk for glucose-6-phosphate dehydrogenase (G6PD) deficiency

 

Aiding in the diagnosis of G6PD deficiency

 

Determining G6PD deficiency status in individuals with inconclusive or unexpected phenotyping results

 

Differentiation of heterozygous females with skewed X-inactivation from homozygous and compound heterozygous females

 

Definitive diagnosis of carrier status in females

 

Evaluation of neonates (particularly males) with unexplained jaundice

 

Identifying individuals at risk of drug-induced acute hemolytic anemia (AHA) related to G6PD deficiency

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

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a very common X-linked condition, impacting about 400 million people worldwide. Both males and females may be impacted due to how common G6PD deficiency is in the population.

 

Several medications, including rasburicase, methylene blue and dapsone, result in acute hemolytic anemia (AHA) when taken by individuals with G6PD deficiency.

 

FDA labeling and Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines recommend that G6PD testing be undertaken in high-risk populations before prescribing drugs known to cause AHA. Knowing a patient's genotype is generally sufficient to avoid contraindicated drugs, but follow-up with the phenotyping enzyme assay may be necessary to clarify results in some cases.

 

This test involves full gene sequencing of all exons and intron/exon boundaries of the G6PD gene. A comprehensive interpretation will be provided including congenital and pharmacogenomic implications of results. Testing should be considered before prescribing medication associated with hemolysis in individuals with G6PD deficiency.

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

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzymopathy with about 400 million people affected worldwide. It is most commonly found in populations where Plasmodium falciparum malaria is (or was) endemic, but G6PD deficiency may be present in any population.

 

G6PD converts glucose-6-phosphate to 6-phosphoglyconolactone in the first step of the pentose phosphate pathway (PPP), this reaction also produces nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) from nicotinamide adenine dinucleotide phosphate (NADP). NADPH, through subsequent enzymatic reactions, protects erythrocytes from damage by detoxifying hydrogen peroxide and other sources of oxidative stress.

 

G6PD is encoded by the gene G6PD, which lies on the X-chromosome. G6PD deficiency is inherited in an X-linked recessive manner; therefore, males are more commonly affected than females, but due to the high prevalence of G6PD deficiency, homozygous and compound heterozygous females are not uncommon. A large number of G6PD pathogenic variants have been discovered. These variants are subdivided into a class system based on definitions from the World Health Organization (WHO).

 

 Table 1. G6PD variant WHO class and associated G6PD deficiency phenotype

WHO class

Associated Clinical Presentation

G6PD activity

I

Chronic nonspherocytic hemolytic anemia (CNSHA)

<10%

II

Asymptomatic unless challenged

<10%

III

Asymptomatic unless challenged

10%-60%

IV

None

Normal

 

With the exception of those with chronic nonspherocytic hemolytic anemia (CNSHA), individuals with G6PD deficiency are typically asymptomatic until they are challenged with an exogenous factor such as a drug, infection, or fava beans. The exogenous factor can trigger acute hemolytic anemia (AHA) in individuals with G6PD deficiency. The severity of AHA is highly variable, ranging from mild to life-threatening and can be fatal. Therefore, determining the G6PD deficiency status is recommended on the Food and Drug Administration label of several drugs either proven or suspected to cause AHA in patients with G6PD deficiency. For a list of drugs known to cause AHA in individuals with G6PD deficiency, see Pharmacogenomic Associations Tables in Special Instructions.

 

Preemptive genotyping allows for the identification of patients at risk for an adverse reaction to drugs known to cause AHA in those with G6PD deficiency. In most cases, genotyping provides sufficient information to avoid the use of contraindicated drugs. In some cases, including heterozygous females, the phenotyping assay is necessary to determine if such drugs should be avoided. Skewed X-inactivation in heterozygous females has been reported to result in G6PD deficiency, but the phenotyping assay is necessary to determine G6PD activity level. For more information regarding the need for G6PD enzyme activity follow-up testing to this genotyping assay, refer to the G6PD Genotyping Algorithm for Therapeutic Drug Recommendations in Special Instructions.

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

All detected alterations will be evaluated according to the latest American College of Medical Genetics and Genomics recommendations.(1) Variants will be classified based on known, predicted, or possible effect on gene pathogenicity and reported with interpretive comments detailing their potential or known significance.

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

Patients who have received a heterologous blood transfusion within the preceding 6 weeks, or who have received an allogeneic blood or marrow transplant, can have inaccurate genetic test results due to the presence of both donor and recipient DNA.

 

For patients who have been transfused within the preceding 6 weeks, the enzyme assay G6PD1 / Glucose-6-Phosphate Dehydrogenase Enzyme Activity, Blood will also be affected, so it is not an appropriate alternative test.

 

Patients who have received an allogeneic blood or marrow transplant would be expected to convert G6PD status to that of donor. However, if the patient's transplant was partially successful or if there is a relapse of an underlying hematologic malignancy, a mixture of donor and recipient genotype may be seen on genetic analysis. The enzyme assay can be run after transplantation: order G6PD1 / Glucose 6-Phosphate Dehydrogenase Enzyme Activity, Blood.

 

Rare variants exist that could lead to false-negative or false-positive results. Other variants in the primer binding regions can affect the testing, and ultimately, the genotype assessment made.

 

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Large deletions or rearrangements are not detected by this assay.

 

Sometimes a genetic alteration of unknown significance may be identified. In this case, testing of appropriate family members may be useful to determine pathogenicity of the alteration.

 

This test is not designed to provide specific dosing or drug selection recommendations and is to be used as an aid to clinical decision making only. Drug-label guidance should be used when dosing patients with medications regardless of the predicted phenotype.

 

Skewed X-inactivation in heterozygous females has been reported to result in G6PD deficiency, but the phenotyping assay is necessary to determine G6PD activity level and assign G6PD deficiency status in these cases.

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;(17):105-423

2. Cappellini MD, Fiorelli G: Glucose-6-phosphate dehydrogenase deficiency. Lancet. 2008;371:64-67

3. Luzzatto L, Seneca E: G6PD deficiency: a classic example of pharmacogenetics with on-going clinical implications. Br J Haematol. 2014;164:469-480

4. OMIM: 305900 Glucose-6-phosphate dehydrogenase. Johns Hopkins University; 1987. Updated August 5, 2019. Accessed December 4, 2020. Available at www.omim.org/entry/305900

5. Relling MV, McDonagh EM, Chang T, et al: Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for rasburicase therapy in the context of G6PD deficiency genotype. Clin Pharmacol Ther. 2014 Aug;96(2):169-174

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

Genomic DNA is extracted from whole blood. The G6PD gene is amplified by polymerase chain reaction (PCR). The PCR products are then purified and sequenced in both directions using fluorescent dye-terminator chemistry. Sequencing products are separated on an automated sequencer and trace files analyzed for variations in the exons and intron/exon boundaries of all exons using variant detection software and visual inspection. Variant nomenclature is based on GenBank accession number NM_001042351.2 using human genome assembly GRCh37 (hg19).(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

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.

3 to 7 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 or saliva: 2 weeks; Extracted DNA: 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.

81249

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