Sign in →

Test Code G6PD1 Glucose 6-Phosphate Dehydrogenase Enzyme Activity, Blood


Specimen Required


Collection Container/Tube:

Preferred: Yellow top (ACD solution B)

Acceptable: Lavender top (EDTA) or yellow top (ACD solution A)

Specimen Volume: 6 mL

Collection Instructions: Send specimen in original tube. Do not aliquot.


Useful For

Evaluation of individuals with episodic or chronic Coombs-negative nonspherocytic hemolytic anemia

 

Rapid testing to assess glucose 6-phosphate dehydrogenase (G6PD) enzyme capacity prior to rasburicase or other therapies that may cause hemolysis or methemoglobinemia in G6PD deficient patients

 

May aid in the creation of a comprehensive patient profile and can ensure appropriate patient monitoring for developing anemia

Method Name

Kinetic Spectrophotometry

Reporting Name

G6PD Enzyme Activity, B

Specimen Type

Whole Blood ACD-B

Specimen Minimum Volume

1 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Whole Blood ACD-B Refrigerated 20 days

Reference Values

≥12 months of age: 8.0-11.9 U/g Hb

 

Reference values have not been established for patients who are less than 12 months of age.

Interpretation

The World Health Organization (WHO) classification of glucose 6-phosphate dehydrogenase (G6PD) deficiency is historically based on enzyme activity level, and, in most cases, enzyme activity level is sufficient. Accurate classification requires correlation with clinical, and in certain cases, genetic data. The revised WHO classification (2022) has updated classification subtypes from classes I, II, III, IV and V to class A, B, C and U.

 

The Advisory Group panel concluded:(3)

"In future, G6PD variants should be classified based on the median residual enzyme activity expressed as a percentage of normal activity. It should be emphasized that this system is for classifying genetic variants of G6PD and should not be used to classify individual patients with G6PD deficiency. Currently, no variants have been identified in homozygous deficient females or hemizygous deficient males that have median G6PD enzyme activity falling between 45% and 60%. Therefore, a gap has been left between Classes B and C. If new variants are found with median G6PD enzyme activity in this range, these should be included in the "U" class and studied until solid evidence is found that they induce acute haemolytic anaemia (= Class B) or do not pose a haemolytic risk (= Class C). Based on new evidence, the thresholds may then need to be revisited."

 

Table. Updated (2022) 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

 

 

*The activity is per variant (ie, per allele) and most straightforward to assess in hemizygous male patients and homozygous female patients. Compound heterozygous female patients are more complex and rely on clinical and familial correlation.

**Legacy WHO Class V: increased activity (enzyme activity >150%) has been discontinued in the 2022 recommendations. It was originally created due to a single variant that has not been corroborated and is not deemed clinically relevant.

 

Although G6PD deficiency is an X-linked recessive disorder and most often seen in hemizygous male patients, some female patients are affected. In addition, older women who are heterozygous can develop deficiency due to differential X-skewing with age.(4) It is important to note that clinically significant G6PD deficiency can be masked in the setting of significant reticulocytosis, markedly elevated white blood cell count, or recent red blood cell transfusion. If any of these are present in the setting of a history of neonatal, chronic, or episodic jaundice or anemia, genotyping for G6PD genetic alterations is recommended. If desired, order G6PDZ / Glucose-6-Phosphate Dehydrogenase (G6PD) Full Gene Sequencing, Varies.

Clinical Reference

1. Cappellini MD, Fiorelli G. Glucose-6-phosphate dehydrogenase deficiency. Lancet. 2008;371(9606):64-74

2. Glucose-6-phosphate dehydrogenase deficiency. WHO Working Group. Bull World Health Organ. 1989;67(6):601-611

3. Global Malaria Programme, Malaria Policy Advisory Group. Meeting report of the technical consultation to review the classification of glucose-6-phosphate dehydrogenase (G6PD). World Health Organization; 2022. Accessed October 10, 2023. Available at www.who.int/publications/m/item/WHO-UCN-GMP-MPAG-2022.01

4. Au WY, Ma ES, Lam VW, et al. 6-phosphate dehydrogenase (G6PD) deficiency in elderly Chinese women heterozygous for G6PD variants. Am J Med Genet A. 2004;129A(2):208-211

5. ELITEK (rasburicase). Package insert: Sanofi-aventis; Updated December 2019. Accessed October 22, 2020; Available at products.sanofi.us/elitek/Elitek.html

6. 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;96(2):169-174

7. Robinson KM, Yang W, Haider CE, et al. Concordance between glucose-6-phosphate dehydrogenase (G6PD) genotype and phenotype and rasburicase use in patients with hematologic malignancies. Pharmacogenomics J. 2019;19(3):305-314. doi:10.1038/s41397-018-0043-3

8. Mohammad S, Clowse MEB, Eudy AM, Criscione-Schreiber LG. Examination of hydroxychloroquine use and hemolytic anemia in G6PDH-deficient patients. Arthritis Care Res (Hoboken). 2018;70(3):481-485. doi:10.1002/acr.23296

9. Mandi G, Witte S, Meissner P, et al. Safety of the combination of chloroquine and methylene blue in healthy adult men with G6PD deficiency from rural Burkina Faso. Trop Med Int Health. 2005;10(1):32-38

10. PLAQUENIL Hydroxychloroquine Sulfate Tablets, USP. Package insert: Concordia Pharmaceuticals Inc; 2015 Updated January 2017. Accessed October 20, 2023. Available at www.accessdata.fda.gov/drugsatfda_docs/label/2017/009768s037s045s047lbl.pdf

11. Minucci A, Moradkhani K, Hwang MJ, et al. Glucose-6-phosphate dehydrogenase (G6PD) mutations database: Review of the "old" and update of the new mutations. Blood Cells Mol Dis. 2012;48(3):154-165

12. Beutler E. Glucose-6-phosphate dehydrogenase deficiency. In: Beutler E, Lichtman MA, Coller BS, Kipps TJ. Hematology. 5th ed. McGraw-Hill Book Company; 1995:564-586

13. Mehta A, Mason PJ, Vulliamy TJ. Glucose-6-phosphate dehydrogenase deficiency. Baillieres Best Pract Res Clin Haematol. 2000;13(1):21-38

14. Koralkova P, van Solinge WW, van Wijk R. Rare hereditary red blood cell enzymopathies associated with hemolytic anemia-pathophysiology, clinical aspects and laboratory diagnosis. Int J Lab Hematol. 2014;36:388-397

15. Luzzatto L, Ally M, Notaro R. Glucose-6-phosphate dehydrogenase deficiency. Blood. 2020;136(11):1225-1240. doi:10.1182/blood.2019000944

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

82955

LOINC Code Information

Test ID Test Order Name Order LOINC Value
G6PD1 G6PD Enzyme Activity, B 32546-4

 

Result ID Test Result Name Result LOINC Value
G6PCL G6PD Enzyme Activity, B 32546-4

Day(s) Performed

Monday through Friday

Report Available

1 to 4 days

Forms

If not ordering electronically, complete, print, and send a Benign Hematology Test Request (T755) with the specimen.