Abstract
Background : Glucose-6-phosphate dehydrogenase (G6PD) deficiency
is a common X-linked enzyme disorder associated with hemolytic anemia
after exposure to certain medications or foods. Activity testing is the
gold standard for detecting G6PD deficiency; however, this test is
affected by various hematologic parameters. Clinical G6PDgenotyping is included in pharmacogenetic arrays and clinical sequencing
and may be reconciled with activity results.
Methods : Patients (n=1,391) enrolled on an institutional
pharmacogenetic testing protocol underwent clinical G6PDgenotyping for 164 G6PD variants. For the 446 patients with G6PD
activity results, algorithms were designed to assign G6PD status,
accounting for known interferences with the activity assay and forG6PD genotype results. We developed clinical decision support
alerts to inform prescribers when high-risk medications were prescribed,
warning of gene-drug interactions and recommending therapy alteration.
Results : Of 1,391 patients with genotype, 1,334 (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 5 patients with discordant genotype
and activity results: 3 switched from normal to deficient, and 2
switched from deficient to normal.
Conclusion : G6PD activity and genotyping are two independent
testing methods which can be used in conjunction to assign a more
informed G6PD phenotype than either method alone.