Glucose-6-Phosphate Dehydrogenase

Last Literature Review: October 2025 Last Update:

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common enzymatic disorders. Pathogenic variants in the X-linked gene, G6PD, can increase the risk for red blood cell (RBC) hemolysis, anemia, and other complications like neonatal jaundice. Individuals with G6PD deficiency may remain asymptomatic until exposed to an exogenous hemolytic trigger that induces oxidative stress, such as bacterial or viral infections, ingestion of fava beans, or certain medications.  Complete G6PD deficiency is incompatible with life so affected individuals exhibit a spectrum of partial enzyme deficiency. G6PD deficiency occurs worldwide but is most prevalent in individuals from malaria-endemic regions, as G6PD deficiency may confer a selective advantage against malaria. 

Indications for Use

This is the preferred initial screening test for G6PD deficiency.

For genetic testing in individuals of African descent, refer to Glucose-6-Phosphate Dehydrogenase (G6PD) 2 Mutations (0051684); for genetic testing in individuals with other high-risk ethnic backgrounds, refer to Glucose-6-Phosphate Dehydrogenase Deficiency (G6PD) Sequencing (3004457).

Test Interpretation

Methodology

This quantitative assay measures enzymatic activity of G6PD in whole blood, with results normalized to hemoglobin concentration to account for variability in RBC counts. G6PD activity is interpreted by comparing results to age-specific reference intervals (Table 1). Additionally, enzyme activity can be compared to the percentage of the median normal enzyme activity for that age group (Table 2), which aligns with the World Health Organization’s (WHO) criteria for correlating G6PD activity phenotype and G6PD genotype  (Table 3). However, confirmatory genetic testing is required to confirm the genotype and identify G6PD variants.

Interpretative Information

Table 1: Age-Specific Reference Intervals
Age RangeReference Interval
<8 days16.4-24.1
8-30 days13.6-23.9
1-6 months11.5- 21.5
7-12 months10.3- 17.9
1-17 years9.7- 16.9
≥18 years9.6- 16.3
Measured in U/g Hb (units of G6PD activity per gram of hemoglobin)
Table 2: Percentages of Normal Activity
Age100%80%30%
<8 days19.715.85.9
8-30 days18.214.615.5
1-6 months16.112.94.8
7-12 months13.811.04.1
1-17 years12.910.33.9
≥18 years12.710.23.8
Measured in U/g Hb
Table 3: G6PD Activity-Based Phenotype and Presumed Genotype Interpretation
 % of Normal ActivityG6PD Activity PhenotypePresumed G6PD genotype
Males<30%DeficientHemizygous for a G6PD deficient allele
≥30%NormalHemizygous for a G6PD normal allele
Females<30%DeficientHomozygous for G6PD deficient alleles or heterozygous for a G6PD deficient allele with a predominant G6PD deficient RBC population
≥80%NormalHomozygous for G6PD normal alleles or heterozygous for a G6PD normal allele with a predominant G6PD normal RBC population
30-80%IntermediateHeterozygous for a G6PD deficient allele and a G6PD normal allele
Source: WHO 

Factors Affecting Interpretation

  • A recent transfusion with non-G6PD deficient donor RBCs may mask G6PD deficiency.
  • Samples collected during or shortly after a hemolytic episode may yield falsely normal or elevated G6PD activity results as reticulocytes have significantly higher G6PD activity than mature RBCs. If no other cause of hemolysis is identified, repeat G6PD testing is recommended at least 2-3 months after a hemolytic episode. 

References