Glucose-6-Phosphate-Dehydrogenase Deficiency (Copy)

Certain antimalarial drugs, such as the 8-aminoquinoline primaquine, may be contraindicated (or require dosage adjustment) in subjects with glucose-6-phosphate-dehydrogenase (G6PD) deficiency. 

G6PD deficiency testing is most commonly based on phenotype, which can be assessed using qualitative or quantitative tests.

• Qualitative test results are categorized as normal or deficient. Some semi-quantitative tests also provide an intermediate result. Examples of currently available tests include the Fluorescence Spot Test and G6PD rapid diagnostic tests. Performance of marketed qualitative point-of-care tests varies. In addition, the test inherent G6PD activity threshold levels for defining deficiency vary depending on the test applied. Therefore, recording the trade name, manufacturer, batch, etc. is important.
• Quantitative test results are expressed as international units (IU or U) and need to be normalized by grams of hemoglobin (Hgb) per deciliter (dL) or RBC count. Minimal study population characteristics that need to be assessed during field evaluation include the proportion of G6PD-deficient cases in the study population, mean and median G6PD activity of the study population. Mean and median values of G6PD activity need to be stratified by gender and adjusted for ambient temperature and the proportion of G6PD-deficient study participants.^[4] In order to put G6PD activity into context, quantitative results are frequently reported as the fraction (in %) of a population-specific median (the adjusted male median, AMM). Recording the underlying AMM is important; the AMM is defined as the median G6PD activity of all male members of a population after excluding samples with less than 10% of the overall median activity of all males.^[5] Examples of currently available methods include spectrophotometry, handheld quantitative G6PD measurement devices and ELISA based quantitative G6PD assays. Flow cytometry can also be used to determine the proportion of cells that are deficient or not deficient.^[6]

G6PD genotyping is complex and generally not used to guide treatment. There are over 185 G6PD variants associated with a varying degrees of G6PD activity. Symptomatic subjects are usually male, due to the X-linked pattern of inheritance. Females carry two copies of the G6PD gene. Heterozygous females carry one wild type and one mutant version, giving rise to two distinct RBC populations: a G6PD normal and G6PD-deficient population. See the SDTM Implementation Guide for Pharmacogenomics/Genetics (PGx) version 1.0, Section 4.4, Example 1 for additional information on this topic.