G6PD deficiency: a classic example of pharmacogenetics with on‐going clinical implications

Abstract

That primaquine and other drugs can trigger acute haemolytic anaemia in subjects who have an inherited mutation of the glucose 6-phosphate dehydrogenase (G6PD) gene has been known for over half a century: however, these events still occur, because when giving the drug either the G6PD status of a person is not known, or the risk of this potentially life-threatening complication is under-estimated. Here we review briefly the genetic basis of G6PD deficiency, and then the pathophysiology and the clinical features of drug-induced haemolysis; we also update the list of potentially haemolytic drugs (which includes rasburicase). It is now clear that it is not good practice to give one of these drugs before testing a person for his/her G6PD status, especially in populations in whom G6PD deficiency is common. We discuss therefore how G6PD testing can be done reconciling safety with cost; this is once again becoming of public health importance, as more countries are moving along the pathway of malaria elimination, that might require mass administration of primaquine. Finally, we sketch the triangular relationship between malaria, antimalarials such as primaquine, and G6PD deficiency: which is to some extent protective against malaria, but also a genetically determined hazard when taking primaquine.

The Economics of Vivax Malaria Treatment

“…Spectrophotometry is the gold standard test of G6PD activity, but requires specialised staff and laboratory facilities [48,49]. Until recently, the only point-of-care test for G6PD deficiency was the fluorescent spot test (FST).…”

Letter to the Editor: Pharmacogenomics and drug therapy

“…2,3,5,6 I fear that its conspicuous absence in this Australian Prescriber article will only reinforce the mistaken triviality of this common condition in the psyche of prescribing doctors.…”

“…2 Its role in acute drug-induced haemolytic anaemia has been known for over half a century. 3 Medicines including primaquine and rasburicase are definite triggers for drug-induced haemolytic anaemia in patients with G6PD deficiency, but other commonly used drugs can also possibly cause it, including some sulphur-containing antibiotics, quinolones, high doses of aspirin and paracetamol.…”

An Audit on Management of G6PD Deficiency Acute Hemolytic Crisis

“…Although G6PD is a critical enzyme in the redox metabolism of all aerobic cells‚ yet its role in the RBCs is more critical because it is the only source of NADPH which directly and via GSH defends these cells against oxidative stress. G6PD deficiency is an example of hemolytic anemia due to interaction between an intra-corpuscular cause and an extra corpuscular cause‚ because in the majority of cases hemolysis is triggered by an exogenous agent [1][2][3][4][5][6][7][8]. The severity of hemolytic anemia varies among individuals with G6PD deficiency.…”