3.2 G6PD phenotype based on genotype and activity
Four hundred forty-six patients had a G6PD activity result in the medical record at the time the genotype result was obtained. Of these, 8 female heterozygous patients (2 with A-(202A_376G)/A genotype, and 6 with A-(202A_376G)/B, A/Asahi genotype) had a normal or provisional normal activity result and were assigned a provisional normal G6PD activity phenotype (Fig. 2).
Four hundred seventeen patients with a normal genotype had activity test results: 415 patients had a concordant normal G6PD activity phenotype and 2 patients had discordant results. Of the 2 with discordant results, 1 was a male with a class IV A variant and 1 was a male with no observed variants, but both had provisional deficient activity (due to initial critically low hemoglobin) and both were subsequently assigned a normal phenotype (Fig. 2). Of the 415 patients with concordant normal genotype and activity results, no variant was observed in 238 males and 154 females, consistent with the wild-type genotype results of B and B/B (class IV), respectively; 10 males were hemizygous for the class IV A variant, 11 females were heterozygous and 2 females were homozygous for the class IV A variant.
Twenty-one patients with deficient genotype (15 males hemizygous and 4 females homozygous for the A-(202A_376G) variant, 1 female homozygous for the A-(968C_376G) variant, and 1 female compound heterozygous for the A-(202A_376G) and A-(968C_376G) variants) had activity test results; 18 patients had a concordant deficient activity result and were assigned a G6PD deficiency phenotype; 3 patients had discordant results, with normal or provisional normal G6PD activity results, and were subsequently reassigned a G6PD deficiency phenotype (Fig. 2). Of these 3 with possible discordances, one patient experienced hemolysis after receiving rasburicase despite having a normal activity result, and two had provisional normal activity results due to a recent RBC transfusion and elevated reticulocyte count, respectively.
Thus, of 446 patients with both activity and genotype measures, having a genotype result changed G6PD status in 5 patients (1.1%): status changed from provisional deficient to normal in 2 patients and from normal or provisional normal to G6PD deficient in 3 patients. In 4 of the 5 cases, abnormal hematologic parameters at the time of the G6PD activity measure could explain the unreliable activity measure, and in the fifth case, drug-induced anemia confirmed a genotype-based diagnosis of G6PD deficiency missed by the activity measure.
In 173 females, the sensitivity of the activity test was 83.33% (35.88-99.58%) and in 265 males the sensitivity was 86.67% (59.54-98.34%).