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Test ID: G6PD Glucose-6-Phosphate Dehydrogenase (G-6-PD), Quantitative, Erythrocytes

Reporting Name

G-6-PD, QN, RBC

Useful For

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

 

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

Clinical Information

Hemolytic disease may be associated with deficiency of erythrocyte enzymes. The most commonly encountered is a deficiency of glucose-6-phosphate dehydrogenase (G6PD).

 

The G6PD locus is on the X chromosome, thus, clinically significant G6PD deficiency is an X-linked recessive disorder and most often seen in hemizygous males.(1) Females are most commonly asymptomatic heterozygotes; however, due to the prevalence of the disorder, affected homozygous or compound heterozygous females occur in ethnic groups where prevalence is high. In addition, elderly women heterozygotes can develop deficiency due to differential X-skewing with age.(2) More than 400 molecular variants of G6PD are known, and the clinical and laboratory features of G6PD deficiency vary accordingly.(1,3) With some variants, there is chronic, life-long hemolysis, but much more commonly, the condition is asymptomatic and only results in susceptibility to acute hemolytic episodes, which may be triggered by some medications, ingestion of fava beans, or stressor events including viral or bacterial infections. G6PD deficiency is also associated with neonatal hyperbilirubinemia.

 

The common G6PD variants occur in specific ethnic groups. Thus, knowledge of the ethnic background of the patient is important. G6PD deficiency has very high frequency in Southeast Asians and is the most common cause of hemolytic disease of the newborn in Southeast Asian neonates. It is also seen in persons of African and Mediterranean descent.

 

Rasburicase therapy is contraindicated in patients with G6PD deficiency. FDA guidelines state to screen patients at higher risk for G6PD deficiency (eg, patients of African or Mediterranean ancestry) prior to starting therapy.(4)

 

Deficiency can be assessed by enzymatic and/or genetic assays. Due to limitations of genetic testing, in most cases it is preferential to perform G6PD enzyme testing to assign G6PD status.(5) However, enzyme activity can be affected by recent red blood cell transfusion, marked reticulocytosis and very high white blood cell count. In these settings, genotyping may be useful for correlation with the red blood cell enzyme level.(6)

 

Due to historic issues with other similar antimalarial medications, it is sometimes questioned if hydroxychloroquine (HCQ) or chloroquine (CQ) therapy may trigger acute hemolytic episodes in some G6PD subtypes. Data is limited in this regard. Available published data did not find hemolytic episodes associated with HCQ therapy in G6PD deficient African American(7) or CQ therapy in G6PD deficient African(8) patients. Both studied populations were assumed to have mild forms of the disorder and data regarding these medications in populations with more severe G6PD phenotypes is lacking. While patients receiving HCQ do not routinely need G6PD levels checked before initiating therapy, testing may be considered in patients who are from ethnic backgrounds with high G6PD variant rates such as those from Mediterranean, African, or Asian descent.

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. WHO class I (chronic) and class II (episodic) variants are associated with baseline enzyme levels less than 10% of mean normal.(1,3) Enzyme levels between 10% and 60% of mean normal can be seen in class III (episodic) variants or female carrier states. Enzyme levels greater than 60% are considered sufficient and can be seen in normal persons, female carrier states or G6PD variants with subclinical effect (WHO class IV). Although G6PD deficiency is an X-linked recessive disorder and most often seen in hemizygous males, some females are affected. In addition, elderly women heterozygotes can develop deficiency due to differential X-skewing with age.(2) It is important to note that clinically significant G6PD deficiency can be masked in the setting of significant reticulocytosis, markedly elevated WBC 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, please order G6PDB / Glucose-6-Phosphate Dehydrogenase (G6PD) Full Gene Sequencing, Varies.

Testing Algorithm

The following algorithms are available in Special Instructions:

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

 

For more information, see Newborn Screening Act Sheet Glucose-6-Phosphate Dehydrogenase Deficiency in Special Instructions.

Analytic Time

1 day

Day(s) and Time(s) Performed

Monday through Sunday

Clinical Reference

1. Cappellini MD, Fiorelli G: Glucose-6-phosphate dehydrogenase deficiency. Lancet 2008 Jan;371(9606):64-74. doi: 10.1016/S0140-6736(08)60073-2

2. 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 Aug 30;129A(2):208-211

3. 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 Mar 15;48(3):154-165. doi: 10.1016/j.bcmd.2012.01.001

4. Food and Drug Administration: Accessed 04/08/2020; Available at: www.accessdata.fda.gov/drugsatfda_docs/label/2009/103946s5083lbl.pdf

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. doi: 10.1038/clpt.2014.97

6. 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 June;19(3):305–314. doi:10.1038/s41397-018-0043-3

7. 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 Mar;70(3):481-485. doi: 10.1002/acr.23296

8. 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 Jan;10(1):32-38

Method Name

Kinetic Spectrophotometry (KS)

Specimen Type

Whole Blood ACD-B


Specimen Required


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 transfer blood to other containers.


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: 8.8-13.4 U/g Hb

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

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

82955

LOINC Code Information

Test ID Test Order Name Order LOINC Value
G6PD G-6-PD, QN, RBC 32546-4

 

Result ID Test Result Name Result LOINC Value
G6PD_ G-6-PD, QN, RBC 32546-4

Forms

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

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