2.3 G6PD phenotype based on genotype and activity
The procedures used for assigning G6PD phenotype based on genotype and clinical activity test are illustrated in Figure 2. For those with normal or deficient genotype, if an activity measure was present, their concordance was assessed. The results were considered concordant if the activity result was in the expected range predicted by genotype (i.e. ≥ 6.3 units/g Hgb for patients with a normal genotype and <6.3 units/g Hgb for patients with a deficient genotype); others were considered discordant. In patients with a normal or deficient genotype we estimated the sensitivity when using the patient’s activity result to predict G6PD phenotype.
Normal G6PD phenotype assignment Patients with no observed deficient alleles by genotype and either a normal activity, provisional normal activity, or provisional deficient activity result were assigned a normal G6PD phenotype (Fig. 2). Deficient G6PD phenotype assignment Patients with a deficient G6PD genotype, regardless of activity, were assigned a G6PD deficiency phenotype. In addition, patients with no observed deficient alleles by genotype but deficient by activity were assigned a G6PD deficiency phenotype, due to the possibility that the patient may have had a deficient G6PD allele not interrogated on the genotyping assay. All patients assigned a deficient phenotype had a G6PD deficiency problem list entry added to their electronic health record. Variable G6PD phenotype assignment Due to X chromosome inactivation, heterozygous females may exhibit G6PD activity ranging from normal to deficient, and G6PD activity may change throughout their lifetime;13,14 for this reason, genotype alone cannot predict G6PD phenotype and heterozygous females are assigned variable phenotype status, and a G6PD activity test was recommended5 if a result was not already present in the EHR. Even those with activity results were assigned a provisional phenotype based on activity, to reflect the potential for a change in G6PD activity and phenotype in the future (Fig. 2). Patients assigned a provisional deficient phenotype had a G6PD deficiency problem list entry added to their electronic health record.