Chronic non-spherocytic haemolytic disorders associated with glucose-6-phosphate dehydrogenase variants

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common huma n enzyme defect, being present in over 400 million people world wide. In a small number of cases, G6PD deficiency can lead to mild-to-severe chronic h aemolysis, which is further exacerbated by oxidative stress. Such G6PD vari ants have been described all over the world and are responsible for chronic non-spherocytic haemolytic anaemia (CNSHA). To date 61 G6PD molecular vari ants associated with CNSHA have been identified, only some of which can cau se the severe reduction in stability of the red blood cell enzyme. The dist ribution of the different mutations shows a predominance of small mutationa l events, and many have been found repeatedly in different parts of the wor ld. By revisiting the 61 class I variants described so far, we can observe that a low inhibition constant (K-i) for NADPH, a higher K-m for substrates and a reduced thermostability are common.