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Test ID: G6PDB Glucose-6-Phosphate Dehydrogenase (G6PD) Full Gene Sequencing

Useful For

Genetic test for individuals at high risk for G6PD deficiency (for initial or time-sensitive screening for G6PD deficiency, refer to phenotyping enzyme assay G6PD / Glucose-6-Phosphate Dehydrogenase [G-6-PD], Quantitative, Erythrocytes)

 

Aiding in the diagnosis of glucose-6-phosphate dehydrogenase (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

Testing Algorithm

The following algorithms are available in Special Instructions:

-G6PD Genotyping Algorithm for Therapeutic Drug Recommendations

-Newborn Screen Follow-up for Glucose-6-Phosphate Dehydrogenase (G-6-PD) Deficiency

Method Name

Polymerase Chain Reaction (PCR) Followed by DNA Sequence Analysis

Reporting Name

G6PD Full Gene Sequencing

Specimen Type

Varies


Necessary Information


1. Patient's sex is required.

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



Specimen Required


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)/Refrigerated

 

Specimen Type: Saliva

Supplies: DNA Saliva Collection Kit (T651)

Container/Tube: Oragene DNA Self-Collection Kit (T651: fees apply)

Specimen Volume: Full tube

Collection Instructions:

1. Fill tube to line.

2. Send specimen in original container per kit instructions.

Specimen Stability Information: Ambient

 

Specimen Type: 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


Specimen Minimum Volume

Blood: 0.45 mL
Saliva: Full tube of saliva

Specimen Stability Information

Specimen Type Temperature Time
Varies Varies

Clinical Information

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 FDA 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 Table 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

An interpretive report will be provided.

Interpretation

All detected alterations will be evaluated according to the latest American College of Medical Genetics 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.

Clinical Reference

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 Available at www.acmg.net/docs/Standards_Guidelines_for_the_Interpretation_of_Sequence_Variants.pdf

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. 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

Day(s) and Time(s) Performed

Monday, Wednesday

Analytic Time

3 days (Not reported on Saturday or Sunday)

Test Classification

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

81479

LOINC Code Information

Test ID Test Order Name Order LOINC Value
G6PDB G6PD Full Gene Sequencing 21680-4

 

Result ID Test Result Name Result LOINC Value
37847 Phenotype 47998-0
48399 Result Details In Process
37848 Interpretation 69047-9
37850 Method 49549-9
37902 Disclaimer 62364-5
38194 Additional Information 48767-8
37851 Reviewed By No LOINC Needed

Forms

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 (T576) is available in Special Instructions.

2. If not ordering electronically, complete, print, and send a Benign Hematology Test Request Form (T755) with the specimen (http://www.mayomedicallaboratories.com/it-mmfiles/benign-hematology-test-request-form.pdf)

Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

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