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.