Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency
Authors: Dr Wilmaré Gouws & Dr Mada Ferreira
Ampath Chat No. 95 – Version 2
Published: May 2025
Introduction
G6PD is a vital housekeeping enzyme in red blood cells (RBCs). It catalyses the oxidation of glucose-6-phosphate to 6-phosphoglucono-lactone, coupled with the reduction of NADP to NADPH. NADPH is essential for protecting cellular structures from oxidative damage caused by free radicals.
Genetics
G6PD deficiency is the most common human enzyme defect, affecting over 400 million people globally. It is an X-linked genetic disorder:
- Males have one allele and can be hemizygous deficient or normal.
- Females have two alleles and can be homozygous deficient, heterozygous (intermediate), or homozygous normal.
More than 200 mutations have been identified in the G6PD gene.
Clinical Presentation
RBCs in G6PD-deficient individuals are more vulnerable to haemolysis under oxidative stress. Most individuals only discover their condition after a haemolytic episode triggered by:
- Certain medications
- Specific foods (e.g., legumes like fava beans, soybeans, peanuts, peas, chickpeas)
- Infections (e.g., hepatitis A/B, pneumonia, typhoid fever)
Haemolytic episodes can range from mild to life-threatening, depending on the G6PD variant, trigger dose and duration, patient age, and coexisting conditions.
Both homozygous and heterozygous females, as well as hemizygous males, should avoid medications known to trigger haemolysis.
G6PD Deficiency in Neonates
Neonates may present with jaundice peaking 2–3 days after birth. If untreated, this can lead to:
- Bilirubin encephalopathy (kernicterus)
- Permanent neurological damage
- Death
G6PD-deficient neonates often have higher bilirubin levels than those with jaundice from other causes, increasing the need for exchange transfusion.
Neonates with a coexisting mutation in the UGT1A1 gene promoter (Gilbert syndrome) are at increased risk of severe jaundice.
Indications for G6PD Testing
- Before treatment with known trigger medications
- After haemolysis following exposure to triggers
- Neonatal haemolytic anaemia (non-spherocytic)
- Congenital non-spherocytic haemolytic anaemia
- Prolonged or severe neonatal jaundice
- Red cell morphology showing oxidative damage (e.g., bite cells)
- Sickle cell disease or thalassaemia
- Favism or family history of G6PD deficiency
- Before starting Rasburicase in oncology patients
- Acute haemolysis post stem cell transplant if donor is G6PD deficient
Diagnostic Testing
Qualitative (Screening) Test
- Rapid and commonly used
- Detects NADPH fluorescence proportional to G6PD levels
- Effective for severe deficiencies but less reliable for intermediate levels
Quantitative (Confirmatory) Test
- Uses a colorimetric system with photometric measurement
- Distinguishes between deficient, intermediate, and normal levels
- Recommended for accurate diagnosis and neonatal management
Test Information
- Mnemonic: G6RET
- Specimen: 1 x EDTA tube
- Turnaround Time: 24 hours (urgent requests must be arranged with a haematopathologist)
- Frequency: Daily
Conclusion
G6PD deficiency is the most common enzyme deficiency in humans. Early diagnosis and avoidance of triggers are essential to prevent haemolysis. Quantitative testing is especially important for managing neonatal jaundice.