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Test Code G6PDZ Glucose-6-Phosphate Dehydrogenase (G6PD) Full Gene Sequencing, 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


 



Specimen Required


Patient Preparation: A previous hematopoietic stem cell transplant from an allogenic donor will interfere with testing. For information about testing patients who have received a hematopoietic stem cell transplant, call 800-533-1710.

 

Submit only 1 of the following specimens:

 

Specimen Type: Whole blood

Container/Tube: Lavender top (EDTA) or yellow top (ACD)

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

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

Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated 4 days/Frozen 4 days

Additional Information:

1. Specimens are preferred to be received within 4 days of collection. Extraction will be attempted for specimens received after 4 days, and DNA yield will be evaluated to determine if testing may proceed.

2. To ensure minimum volume and concentration of DNA is met, the requested volume must be submitted. Testing may be canceled if DNA requirements are inadequate.

 

Specimen Type: Cord blood

Container/Tube: Lavender top (EDTA) or yellow top (ACD)

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

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

Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated 4 days/Frozen 4 days

Additional Information:

1. Specimens are preferred to be received within 4 days of collection. Extraction will be attempted for specimens received after 4 days, and DNA yield will be evaluated to determine if testing may proceed.

2. To ensure minimum volume and concentration of DNA is met, the requested volume must be submitted. Testing may be canceled if DNA requirements are inadequate.

3. While a properly collected cord blood sample may not be at risk for maternal cell contamination, unanticipated complications may occur during collection. Therefore, maternal cell contamination studies are recommended to ensure the test results reflect that of the patient tested and are available at an additional charge. Order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.

 

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 (preferred) 30 days/Refrigerated 30 days

Additional Information: Saliva specimens are acceptable but not recommended. Due to lower quantity/quality of DNA yielded from saliva, some aspects of the test may not perform as well as DNA extracted from a whole blood sample. When applicable, specific gene regions that were unable to be interrogated will be noted in the report. Alternatively, additional specimen may be required to complete testing.

 

Specimen Type: Extracted DNA

Container/Tube:

Preferred: Screw Cap Micro Tube, 2mL with skirted conical base

Acceptable: Matrix tube, 1mL

Collection Instructions:

1. The preferred volume is at least 100 mcL at a concentration of 75 ng/mcL.

2. Include concentration and volume on tube.

Specimen Stability Information: Frozen (preferred) 1 year/Ambient/Refrigerated

Additional Information: DNA must be extracted in a CLIA-certified laboratory or equivalent and must be extracted from a specimen type listed as acceptable for this test (including applicable anticoagulants). Our laboratory has experience with Chemagic, Puregene, Autopure, MagnaPure, and EZ1 extraction platforms and cannot guarantee that all extraction methods are compatible with this test. If testing fails, one repeat will be attempted, and if unsuccessful, the test will be reported as failed and a charge will be applied. If applicable, specific gene regions that were unable to be interrogated due to DNA quality will be noted in the report.


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 1 of the following forms with the specimen:

-Therapeutics Test Request (T831)

-Benign Hematology Test Request Form (T755)

Secondary ID

610053

Useful For

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 heterozygotes with skewed X-inactivation from homozygotes and compound heterozygotes

 

Definitive diagnosis of carrier status

 

Evaluation of neonates with unexplained jaundice

 

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

Genetics Test Information

This test is for molecular sequencing of the G6PD gene and does not assess glucose-6-phosphate dehydrogenase (G6PD) enzyme activity. Enzymatic testing may be suggested as follow-up to this assay. For G6PD enzyme testing order G6PD1 / Glucose 6-Phosphate Dehydrogenase Enzyme Activity, Blood.

 

G6PD deficiency is a common X-linked condition, estimated to affect up to 500 million people worldwide. Both male and female patients may be impacted due to how common G6PD deficiency is in the population.

 

Acute hemolytic anemia (AHA) can be triggered in individuals with G6PD deficiency by fava beans, several types of medications (including rasburicase, dapsone-containing combinations of antimalarial drugs, and methylene blue), and infection. Less commonly, chronic congenital nonspherocytic hemolytic anemia (CNSHA) may occur in severe forms of G6PD deficiency.

 

US Food and Drug Administration 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 exon/intron 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.

Method Name

Polymerase Chain Reaction (PCR) followed by DNA Sequence Analysis

Reporting Name

G6PD Full Gene Sequencing, V

Specimen Type

Varies

Specimen Minimum Volume

See Specimen Required

Specimen Stability Information

Specimen Type Temperature Time
Varies Varies

Reject Due To

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

Clinical Information

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzymopathy, estimated to affect up to 500 million people worldwide. It is most frequently found in populations where Plasmodium falciparum malaria is (or was) endemic, but G6PD deficiency may be present in any population.(1)

 

Glucose-6-phosphate dehydrogenase deficiency primarily manifests as episodic acute hemolytic anemia (AHA), chronic non-spherocytic hemolytic anemia (CNSHA), and neonatal jaundice. These clinical manifestations can be triggered in individuals with G6PD deficiency by fava beans, several types of medications (including rasburicase, dapsone-containing combinations of antimalarial drugs, and methylene blue), and infection.(1,2)

 

Glucose-6-phosphate dehydrogenase converts glucose-6-phosphate to 6-phosphoglyconolactone in the first step of the pentose phosphate pathway, this reaction also produces nicotinamide adenine dinucleotide phosphate (NADPH) from NADP(+). NADPH, through subsequent enzymatic reactions, protects erythrocytes from damage by detoxifying hydrogen peroxide and other sources of oxidative stress. (3)

 

Glucose-6-phosphate dehydrogenase is encoded by the gene G6PD, which lies on the X-chromosome. G6PD deficiency is inherited in an X-linked recessive manner; therefore, male patients are more commonly affected than female patients, but due to the high prevalence of G6PD deficiency, homozygous and compound heterozygous female patients are not uncommon. Over 200 G6PD variants have been discovered and are classified based on guidance from the World Health Organization (WHO). In 2022, WHO proposed updated guidance for the classification of G6PD variants (Table).(4) This revised guidance is based on the median residual enzyme activity and seeks to resolve problems identified with the WHO G6PD classification system that has been in place since 1985 (Table).(4)

 

Table. Updated and Legacy G6PD Variant WHO Classification and Associated G6PD Deficiency Phenotype

2022 WHO class

Median G6PD activity

Hemolysis

Legacy WHO class

Level of residual enzyme activity (% of normal)

A

<20%

Chronic (CNSHA)

I

<10%

B

<45%

Acute, triggered

II

<10%

III

10%-60%

C

60-150%

No hemolysis

IV

Normal

U

Any

Uncertain clinical significance

 

 

 

With the exception of those with CNSHA, individuals with G6PD deficiency are typically asymptomatic until they are challenged with an exogenous factor, such as a drug, infection, or fava beans.(1) The exogenous factor can trigger AHA in individuals with G6PD deficiency. The severity of AHA is highly variable, ranging from mild neonatal jaundice to life-threatening complications, such as kernicterus.(1) Therefore, determining the G6PD deficiency status is recommended on the US Food and Drug Administration label of several drugs either proven or suspected to cause AHA in patients with G6PD deficiency. For more information on drugs known to cause AHA in individuals with G6PD deficiency, see Pharmacogenomic Associations Tables. In addition, the Clinical Pharmacogenetics Implementation Consortium has published a guideline related to medication use in the context of G6PD genotype.(5)

 

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 female patients, the phenotyping assay is necessary to determine if such drugs should be avoided. Skewed X-inactivation in heterozygous female patients has been reported to result in G6PD deficiency, so the phenotyping assay is necessary to determine G6PD activity level.(3)

Reference Values

An interpretive report will be provided.

Interpretation

All detected alterations will be evaluated according to the latest American College of Medical Genetics and Genomics recommendations and the most recent World Health Organization system for classifying genetic variants of G6PD.(1,2) 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.

Day(s) Performed

Varies

Report Available

3 to 7 days

Specimen Retention Time

Whole blood: 28 days (if available); Saliva: 30 days (if available), Extracted DNA: 3 months

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information

81249

LOINC Code Information

Test ID Test Order Name Order LOINC Value
G6PDZ G6PD Full Gene Sequencing, V 94231-8

 

Result ID Test Result Name Result LOINC Value
618837 G6PD Phenotype 47998-0
618838 Result Details 82939-0
618839 Interpretation 69047-9
618840 Additional Information 48767-8
618841 Method 85069-3
618842 Disclaimer 62364-5
618843 Reviewed By 18771-6

Testing Algorithm

For cord blood specimens that have an accompanying maternal blood specimen, maternal cell contamination studies will be performed at an additional charge.

 

The following are available:

-Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency Diagnostic Algorithm

-Glucose-6-Phosphate Dehydrogenase (G6PD) Genotyping Interpretive Algorithm

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
MATCC Maternal Cell Contamination, B Yes No