Why Are There So Many False Negative G6PD Tests?

An estimated 700 million people (around 10% of the global population) is G6PD deficient. The diagnosis of G6PD deficiency is commonly made, by a rapid fluorescent spot test detecting the generation of NADPH from NADP.

The test is positive if the blood spot fails to fluoresce under ultraviolet light.

In patients who have recently hemolyzed, the test results for G6PD deficiency may be falsely negative because the older red blood cells with a higher enzyme deficiency have been hemolyzed (destroyed).

Young red blood cells have normal or near-normal enzyme activity even in G6PD deficiency.

Female heterozygotes (carriers) may be hard to diagnose because of X-chromosome mosaicism (being composed of cells of two genetically different types) leading to a partial deficiency that will not be detected reliably with screening tests.