Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the commonest red blood cell enzyme defect. It is more common in people from the Mediterranean and Africa and is inherited in an X-linked recessive fashion. Many drugs can precipitate a crisis as well as infections and broad (fava) beans
Pathophysiology
- G6PD is the first step in the pentose phosphate pathway, which converts glucose-6-phosphate→ 6-phosphogluconolactone
- this reaction also results in nicotinamide adenine dinucleotide phosphate (NADP) → NADPH
- i.e. glucose-6-phosphate + NADP → 6-phosphogluconolactone + NADPH
- NADPH is important for converting oxidizied glutathine back to it's reduced form
- reduced glutathine protects red blood cells from oxidative damage by oxidants such as superoxide anion (O2-) and hydrogen peroxide
- ↓ G6PD → ↓ reduced NADPH → ↓ reduced glutathione → increased red cell susceptibility to oxidative stress
Features
- neonatal jaundice is often seen
- intravascular haemolysis
- gallstones are common
- splenomegaly may be present
- Heinz bodies on blood films. Bite and blister cells may also be seen
Diagnosis is made by using a G6PD enzyme assay
- levels should be checked around 3 months after an acute episode of hemolysis, RBCs with the most severely reduced G6PD activity will have hemolysed → reduced G6PD activity → not be measured in the assay → false negative results
Some drugs causing haemolysis
- anti-malarials: primaquine
- ciprofloxacin
- sulph- group drugs: sulphonamides, sulphasalazine, sulfonylureas
Some drugs thought to be safe