Test ID: G6PDB Glucose-6-Phosphate Dehydrogenase (G6PD) Full Gene Sequencing, Varies
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 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 are available in Special Instructions:
-G6PD Genotyping Algorithm for Therapeutic Drug Recommendations
-Newborn Screen Follow-up for Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency
-Newborn Screening Act Sheet Glucose-6-Phosphate Dehydrogenase Deficiency
Special Instructions
- Informed Consent for Genetic Testing
- Pharmacogenomic Associations Tables
- G6PD Genotyping Algorithm for Therapeutic Drug Recommendations
- Newborn Screening Act Sheet Glucose-6-Phosphate Dehydrogenase Deficiency
- Newborn Screen Follow-up for Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency
- Informed Consent for Genetic Testing (Spanish)
Method Name
Polymerase Chain Reaction (PCR) followed by DNA Sequence Analysis
Reporting Name
G6PD Full Gene SequencingSpecimen Type
VariesOrdering 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
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
Specimen Minimum Volume
Blood: 0.45 mL
Saliva: 1 swab
Specimen Stability Information
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
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 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
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.(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
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
Day(s) Performed
Monday, Wednesday
Report Available
3 to 7 daysTest 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 US Food and Drug Administration.CPT Code Information
81249
LOINC Code Information
Test ID | Test Order Name | Order LOINC Value |
---|---|---|
G6PDB | G6PD Full Gene Sequencing | 94231-8 |
Result ID | Test Result Name | Result LOINC Value |
---|---|---|
37847 | Phenotype | 47998-0 |
48399 | Result Details | 82939-0 |
37848 | Interpretation | 69047-9 |
37850 | Method | 85069-3 |
37902 | Disclaimer | 62364-5 |
38194 | Additional Information | 48767-8 |
37851 | Reviewed By | 18771-6 |
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)
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