Incorporating G6PD genotyping to identify patients with G6PD deficiency

Glucose-6-phosphate-dehydrogenase (G6PD) deficiency is a common X-linked enzyme disorder associated with hemolytic anemia after exposure to fava beans or certain medications. Activity testing is the gold standard for detecting G6PD deficiency; however, this test is affected by various hematologic parameters. Clinical G6PD genotyping is now included in pharmacogenetic arrays and clinical sequencing efforts and may be reconciled with activity results. Patients (n = 1391) enrolled on an institutional pharmacogenetic testing protocol underwent clinical G6PD genotyping for 164 G6PD variants. An algorithm accounting for known interferences with the activity assay is proposed. We developed clinical decision support alerts to inform prescribers when high-risk medications were prescribed, warning of gene-drug interactions and recommending therapy alteration. Of 1391 patients with genotype results, 1334 (95.9%) patients were predicted to have normal G6PD activity, 30 (2.1%) were predicted to have variable G6PD activity and 27 (2%) were predicted to have deficient G6PD activity. Of the 417 patients with a normal genotype and an activity result, 415 (99.5%) had a concordant normal G6PD phenotype. Of the 21 patients with a deficient genotype and an activity result, 18 (85.7%) had a concordant deficient activity result. Genotyping reassigned phenotype in five patients with discordant genotype and activity results: three switched from normal to deficient, and two switched from deficient to normal. G6PD activity and genotyping are two independent testing methods that can be used in conjunction to assign a more informed G6PD phenotype than either method alone.

Automated summary

G6PD deficiency is a common enzyme disorder associated with hemolytic anemia. Clinical G6PD genotyping and activity testing are two commonly used methods that can be used together to determine the G6PD phenotype more accurately.