G6PD Deficiency
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Direct answer
G6PD deficiency is an X-linked recessive defect of the glucose-6-phosphate dehydrogenase enzyme, leaving red cells unable to regenerate NADPH and protect haemoglobin from oxidant stress. Affected males and homozygous females develop acute haemolysis after triggers such as fava beans, infection or certain drugs, with Heinz bodies and bite cells on the blood film. Its main clinical links in India are neonatal jaundice and screening before primaquine.
What you must remember
- Inheritance: X-linked recessive, so males are affected, while heterozygous females are carriers whose enzyme activity varies with X inactivation.
- Trigger-driven haemolysis: acute intravascular haemolysis, often 24 to 72 hours after exposure, with dark urine and anaemia.
- Blood film: Heinz bodies, which need a supravital stain, along with bite cells and blister cells.
- Triggers: fava beans (favism), infections, and drugs such as primaquine, dapsone, sulfonamides, nitrofurantoin, rasburicase and methylene blue.
- Neonatal jaundice: a recognised cause of unconjugated hyperbilirubinaemia in endemic regions, sometimes needing exchange transfusion in severe cases.
- Diagnosis: quantitative enzyme assay, ideally after the haemolytic episode, because reticulocytosis can give a falsely normal result.
A trigger-based approach to diagnosis and care
The clinical course is driven by exposure, so the key skill is identifying the trigger and then planning avoidance and screening.
- Take an exposure history: ask about fava beans, recent infection, antimalarials, antibiotics and any new drug or topical agent, since the trigger is often the diagnosis.
- Examine the blood film: Heinz bodies and bite cells support oxidative haemolysis, and the reticulocyte count shows marrow compensation.
- Check haemolysis markers: indirect bilirubin, LDH and haptoglobin, with a direct Coombs test to exclude autoimmune haemolysis.
- Measure enzyme activity: a quantitative assay is done once the child is stable, because recent transfusion or reticulocytosis can mask deficiency.
- Support and treat: supportive care, transfusion for severe anaemia, and phototherapy for neonatal hyperbilirubinaemia.
- Counsel and screen family: avoid triggers, carry a list of unsafe drugs, and screen at-risk relatives.
Mild deficiency may cause no symptoms until a trigger appears, so a normal clinical life does not exclude the diagnosis. Screening before primaquine and before rasburicase is the most valuable preventive step.
Where the exam tries to catch you
G6PD questions often hinge on a single drug or a single neonatal clue.
- Trap: giving primaquine without G6PD screening Correct: primaquine can cause severe haemolysis in deficient patients, so status must be known first.
- Trap: labelling neonatal jaundice physiological without considering G6PD Correct: especially with a haemolytic picture, G6PD deficiency is a recognised cause.
- Trap: testing enzyme activity during acute haemolysis Correct: young reticulocytes carry more enzyme and can make the assay falsely normal, so repeat testing later.
- Trap: assuming heterozygous females are unaffected Correct: they can show variable haemolysis through random X inactivation.
Frequently asked questions
Why is G6PD deficiency more common in males?
G6PD deficiency is X-linked recessive, so males who inherit one defective gene are affected. Females usually carry the defect without symptoms, although variable X inactivation can cause haemolysis in heterozygous females.
Which drugs must be avoided in G6PD deficiency?
Primaquine, dapsone, sulfonamides such as cotrimoxazole, nitrofurantoin and rasburicase are classic drugs to avoid in G6PD deficiency. The standard drug list should be checked before prescribing for any at-risk child.
What is the classic neonatal presentation of G6PD deficiency?
Neonatal G6PD deficiency presents with unconjugated hyperbilirubinaemia, often in the first days of life, sometimes with haemolytic anaemia. It is an important cause of jaundice in endemic regions, particularly when onset is early or severe.
Why can a G6PD assay be falsely normal?
During acute haemolysis or after transfusion, the red cell population includes young reticulocytes with more enzyme, which can give a falsely normal result. Repeating the assay after recovery avoids this error.
Which blood film finding is typical of oxidant haemolysis?
Heinz bodies, which are denatured haemoglobin inclusions seen with supravital staining, and bite cells are typical after an oxidant trigger in G6PD deficiency. These findings are not specific, so the enzyme assay confirms the diagnosis.