What are normal Glucose-6-Phosphate Dehydrogenase (G6PD) levels?

Normal G6PD Levels

Normal G6PD enzyme activity in adults is approximately 3.50 ± 0.8 μmol/min/g tissue in liver, while in blood the reference range is approximately 11.7-13.6 U/g Hb for individuals without G6PD mutations, though this varies by age and testing methodology.

Reference Values by Population and Age

Adults and Older Infants (>30 days)

• Normal individuals without G6PD mutations: 11.7 ± 3.4 U/g Hb 1
• Liver tissue: 3.50 ± 0.8 μmol/min/g tissue 2

Neonates and Young Infants (<30 days)

• Normal individuals without G6PD mutations: 13.6 ± 3.7 U/g Hb 1
• G6PD enzyme activity is negatively correlated with age, with higher levels in younger infants 1

Deficiency Thresholds

Severe Deficiency

• <10% of normal activity is considered severe deficiency, typically detected by qualitative fluorescent spot tests 3
• Hemizygous males: 0.9-2.4 U/g Hb depending on age and variant 4, 1
• In liver tissue, most individuals with GSD Ia show <10% of normal (less than 0.35 μmol/min/g tissue) 2

Intermediate Deficiency

• 10-30% of normal activity represents moderate deficiency 3
• 30-70% activity with non-Mediterranean variants may allow modified treatment regimens with close monitoring 3

Heterozygous Females

• 6.0-6.5 ± 2.0-2.7 U/g Hb across age groups 1
• Enzyme levels range from 6.5-20.1 U/g Hb with no significant difference among different heterozygous variants 4

Critical Testing Considerations

Timing of Testing

• Avoid testing during or immediately after acute hemolytic episodes, as reticulocytes and young RBCs contain near-normal enzyme levels that mask deficiency 3
• Wait at least 50 days after RBC transfusion before performing enzyme assays, as 6-12% donor RBC contamination causes false-negative results 3
• Testing 120 days post-transfusion is ideal but often impractical in frequently transfused patients 3
• In P. vivax infection, G6PD activity remains stable over time (D1, D3, D7, D14, D21, D28), allowing testing on D1 instead of waiting until D14 5

Assay Selection

• Qualitative tests work well for males and homozygous females with severe deficiency 3
• Quantitative assays or flow cytometry are necessary for heterozygous females and patients with concurrent hematological conditions 3
• For tafenoquine use in P. vivax radical cure, quantitative G6PD testing is required—do not use if activity is <70% 2, 3

Sample Processing

• Buffy coat removal or filtration is essential for accurate RBC enzyme measurement 3
• Testing whole blood without removing white cells and platelets prevents detection of deficiency in all cases 3

Clinical Context for Interpretation

Borderline Results

• Calculate the PK/G6PD ratio or compare to controls with similar reticulocyte counts when interpreting borderline results 3
• In the presence of hemolysis, G6PD levels can be elevated, obscuring diagnosis in the newborn period, so a normal level in a hemolyzing neonate does not rule out G6PD deficiency 2
• Repeat testing at 3 months of age if G6PD deficiency is strongly suspected but initial testing is normal 2

Variant-Specific Considerations

• Mediterranean variant (Gdmed) causes life-threatening hemolysis requiring strict oxidant drug avoidance 3
• African variant (GdA-) produces milder, self-limited hemolysis 3
• Molecular analysis may be required in heterozygous females when enzymatic testing is inconclusive 3
• The c.1024C>T (Chinese-5) mutation shows higher enzyme activity than other mutations due to altered kinetic parameters 4

Drug Contraindications

• Primaquine, rasburicase, and methylene blue are absolutely contraindicated in G6PD deficiency 2, 3
• Qualitative screening is recommended before starting oxidant drugs (dapsone, primaquine, sulfonamides) in patients of Mediterranean, African, Indian, or Southeast Asian descent 3