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%).