Ann Lab Med.  2024 Nov;44(6):487-496. 10.3343/alm.2023.0477.

Exploring Appropriate Reference Intervals and Clinical Decision Limits for Glucose-6-Phosphate Dehydrogenase Activity in Individuals From Guangzhou, China

• Huang Z
• Li Z
• Li Y
• Cao Y
• Zhong S
• Liu J
• Lin Z
• Lin L
• Fang Y
• Zeng J
• Su Z
• Li H
• Liang J
• Zhu B
• Lin Z
• Huang Y
• Yang X
• Jiang L

• KMID: 2560795
• DOI: http://doi.org/10.3343/alm.2023.0477

Abstract

Background
Quantitative detection of glucose-6-phosphate dehydrogenase (G6PD) is commonly done to screen for G6PD deficiency. However, current reference intervals (RIs) of G6PD are unsuitable for evaluating G6PD-activity levels with local populations or associating G6PD variants with hemolysis risk to aid clinical decision-making. We explored appropriate RIs and clinical decision limits (CDLs) for G6PD activity in individuals from Guangzhou, China.
Methods
We enrolled 5,852 unrelated individuals between 2020 and 2022 and screened their samples in quantitative assays for G6PD activity. We conducted further investigations, including G6PD genotyping, thalassemia genotyping, follow-up analysis, and statistical analysis, for different groups.
Results
In Guangzhou, the RIs for the G6PD activities were 11.20–20.04 U/g Hb in male and 12.29–23.16 U/g Hb in female. The adjusted male median and normal male median (NMM) values were 15.47 U/g Hb and 15.51 U/g Hb, respectively. A threshold of 45% of the NMM could be used as a CDL to estimate the probability of G6PD variants. Our results revealed high hemolysis-risk CDLs (male: < 10% of the NMM, female: < 30% of the NMM), medium hemolysis-risk CDLs (male: 10%–45% of the NMM, female: 30%–79% of the NMM), and low hemolysis-risk CDLs (male: ≥ 45% of the NMM, female: ≥ 79% of the NMM).
Conclusions
Collectively, our findings contribute to a more accurate evaluation of G6PDactivity levels within the local population and provide valuable insights for clinical decisionmaking. Specifically, identifying threshold values for G6PD variants and hemolysis risk enables improved prediction and management of G6PD deficiency, ultimately enhancing patient care and treatment outcomes.

Keyword

Clinical decision limit; Glucose-6-phosphate dehydrogenase activity; Hemolysis risk, Mutation; Probability; Reference interval

Figure

• 

  Fig. 1 Study protocol. During our preliminary screening, we identified a thalassemia-negative group, a thalassemia-negative group with an abnormal G6PD genotype, and a thalassemia-negative group with a normal G6PD genotype (Groups A–C, respectively). Abbreviations: G6PD, glucose-6-phosphate dehydrogenase; MALDI-TOF MS, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry; MCH, mean corpuscular Hb; MCV, mean corpuscular volume; α, group with α-thalassemia; β, group with β-thalassemia; α/β, group with α/β complex thalassemia; Normal, group with thalassemia and a normal G6PD genotype. *The screening criteria were based on one of our previous studies [25].

• 

  Fig. 2 Distributions of glucose-6-phosphate dehydrogenase (G6PD) activities. (A and B) G6PD-activity distributions in the study population. (C and D) G6PD-activity distributions in Group A (thalassemia-negative group identified during preliminary screening). (E and F) G6PD-activity distributions in Group C (thalassemia-negative group with a normal G6PD genotype identified during preliminary screening). The distributions shown in panels A–D did not follow a normal distribution, whereas those in panels E and F exhibited a normal distribution. *The asterisks indicate the median of each peak.

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  Fig. 3 RIs and CDLs for G6PD activity in individuals from Guangzhou, China. For male, the CDLs were 10% and 45%, the RI was 72%–129%, and NMM2 was used as the 100% value. For female, the CDLs were 30%, 45%, and 79%; the RI was 79%–149%; and NMM2 was used as the 100% value. The G6PD activity (% of normal) is calculated as a percentage by dividing the G6PD (U/g Hb) result by the NMM2 value (15.51 U/g Hb). Abbreviations: RI, reference interval; CDL, clinical decision limit; G6PD, glucose-6-phosphate dehydrogenase; NMM2, normal male median in group 2.

Reference

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