Glucose 6-phosphate dehydrogenase deficiency in an elite long-distance runner.

Glucose 6-phosphate dehydrogenase deficiency in an elite long-distance runner Glucose 6-phosphate dehydrogenase (G6PD) deficiency is the world's most common enzymopathy 1 and caused by mutations in the X-chromosomal G6PD gene. The enzyme catalyzes the first reaction of the hexose monophosphate shunt, which results in 2 main products: pentose phosphate sugars and the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH). The latter is involved in reductive processes. G6PD deficiency is most pronounced in erythrocytes, compared with other cells, because red blood cells lack biosynthetic capacity. Therefore, G6PD-deficient erythrocytes are less able to withstand oxidative stress, leading to (acute) hemolytic anemia. 1 We recently studied a 37-year-old white man who is an elite long distance runner and has attained high class rankings in European, world, and Olympic competitions in the last 15 years while being severely G6PD-deficient. He never showed any clinical signs of hemolysis, and the G6PD deficiency was detected by chance. Routine laboratory investigations showed no abnormalities, except for low haptoglobin and slightly elevated unconjugated bilirubin levels over the years, suggesting the presence of mild chronic hemolysis (Table 1). The athlete's erythrocytes were found to exhibit strongly reduced G6PD activity. G6PD activity in leukocytes was also decreased, though less pronounced. These findings were confirmed by Western blot analysis (Figure 1). DNA analysis revealed a missense mutation in exon 8 (c.844 GϾC: Asp282His) of G6PD. This mutation has been previously found to underlie several biochemically unique G6PD variants. 2 To further characterize the G6PD variant, kinetic measurements were performed using leukocyte-derived G6PD (Table 1). These results led us to conclude that the kinetic properties of the mutant enzyme were only slightly altered. Hence, G6PD deficiency in this athlete appears to be mainly due to the mutant protein's instability, in particular in erythrocytes (Figure 1). Heavy exercise can accelerate the generation of reactive oxygen species (ROS), exceeding the capacity of antioxidant defenses. 3 Because this may result in hemolysis and muscle Table 1. Representative results of routine and specialized laboratory investigations