Genotype-Phenotype Correlations of Glucose-6-Phosphate-Deficient Variants Throughout an Activity Distribution

Area of Science:

• Genetics
• Biochemistry
• Hematology

Background:

• Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked genetic disorder.
• It can cause neonatal jaundice and acute hemolytic anemia.
• Accurate diagnosis requires quantitative assessment of G6PD enzyme activity in erythrocytes.

Purpose of the Study:

• To investigate the association between G6PD genotype and phenotype.
• To establish enzyme activity cutoffs to predict the likelihood of G6PD deficiency.

Main Methods:

• Analyzed DNA from 95 residual samples using Sanger sequencing.
• Employed Receiver Operating Characteristic (ROC) curves to determine diagnostic cutoffs.
• Correlated G6PD enzyme activity levels with identified genetic variants.

Main Results:

• Identified 13 G6PD variant alleles, including one novel variant.
• Established a G6PD activity cutoff of <7.85 U/g Hb for males (100% sensitivity, 94% specificity).
• Established a G6PD activity cutoff of <8.95 U/g Hb for females (90% sensitivity, 82% specificity).

Conclusions:

• Enzyme activity cutoffs can effectively identify G6PD deficiency in males and females.
• These cutoffs may assist in deciding when to pursue genetic testing.
• Observed activity groupings were independent of specific G6PD variant classes.