G6PD activity patterns and a stable adjusted male median derived from 16 years of clinical laboratory data.

Authors

Muhammad Shariq Shaikh, Zeeshan Ansar Ahmed

Published in

Blood research. Volume 61. Issue 1. Aug 14, 2026. Epub Aug 14, 2026.

Abstract

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common enzymopathy worldwide, poses significant clinical and public health challenges, particularly in malaria-endemic regions. Despite the importance of quantitative G6PD activity assessments, clinically meaningful deficiency thresholds remain difficult to define owing to biological variability related to age, sex, and X-linked inheritance. The adjusted male median (AMM) is a recommended framework for defining 100% activity and deriving assay- and region-specific thresholds. However, large-scale evaluations of AMM stability and G6PD activity patterns in Pakistan are limited.
We retrospectively analyzed all quantitative G6PD assays performed at a national reference laboratory in Pakistan between January 2009 and December 2024. Records with valid G6PD activity (U/g hemoglobin (Hb)), age, and sex information were included. Age- and sex-stratified distributions were examined across predefined clinical age groups. The calculated AMM was based on adult males aged 18-45 years (excluding those with ≤ 10% of the initial median). Sensitivity analyses were used to assess AMM stability across alternative adult male age windows (15-50 and 18-60 years). The G6PD activity categories were defined as severe (< 10%), moderate (10-30%), intermediate (30-60%), and normal (> 60%) relative to the AMM.
In total, 51,748 specimens (41,397 from males and 10,351 from females) were analyzed. The median (interquartile range) G6PD activity was 10.3 (7.8-12.6) U/g Hb among males and 10.7 (8.5-12.9) U/g Hb among females. The AMM derived from 7,436 adult males was 9.2 U/g Hb and remained highly stable across alternative age windows (9.2-9.3 U/g Hb; ~ 1% variation). Based on AMM thresholds, 15.4% (95% CI: 15.1-15.7%) of the tested population had < 60% activity, including 6.8% with severe and 4.9% with moderate deficiency. G6PD activity was highest in neonates and infants and declined progressively with age.
The locally derived AMM provides a robust reference standard that reflects the enzymatic capacity within the specific clinical catchment area and serves as a foundation for future clinical validation studies. Age- and sex-specific activity patterns aligned with known physiological and genetic determinants. Although this study provided a locally validated laboratory reference framework, prospective studies correlating the enzymatic categories with clinical outcomes and genotypic data are needed before its broader clinical or public health implementation.

PMID:
42599549
Bibliographic data and abstract were imported from PubMed on 15 Aug 2026.

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