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Deficiency of glucose-6-phosphate dehydrogenase — Clinical Guidelines

Overview

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked enzymopathy characterized by reduced activity of G6PD, leading to increased susceptibility to oxidative stress-induced hemolytic anemia 1 3.

Diagnosis

Quantitative Point-of-Care Tests: Recommended for G6PD activity measurement; SD Biosensor STANDARD G6PD Test shows pooled sensitivity of 0.82 (capillary) and 0.93 (venous) for detecting activity <30% of normal 1.

Capillary vs Venous Blood: Venous blood samples may offer higher sensitivity compared to capillary samples 1.

Laboratory Confirmation: Spectrophotometry serves as the reference method for definitive diagnosis 1.

Management

Avoid Oxidative Stressors: Prevent exposure to drugs like 8-aminoquinolines and high-dose vitamin C, which can trigger hemolysis 2 4.

Supportive Care: Includes packed cell transfusions and management of acute complications like methemoglobinemia 2 4.

Monitoring: Regular monitoring of hemoglobin levels and reticulocyte counts in symptomatic patients 2 4.

Special Populations

Transfusion Medicine: Increased vigilance required in transfusion settings due to risk of hemolysis from oxidative stressors or G6PD-deficient donor RBCs 3.

Elderly: High-dose vitamin therapy should be approached cautiously, given the risk of severe hemolysis 2.

Key Recommendations

Pre-Treatment Screening: Perform G6PD testing before administering 8-aminoquinoline treatments to prevent severe hemolysis (Evidence: Strong 1).

Avoid High-Dose Vitamin C: Exercise caution with high-dose vitamin C infusions, especially in G6PD-deficient individuals, to prevent hemolytic anemia (Evidence: Moderate 2).

Screening in Transfusion Settings: Consider screening for G6PD deficiency in populations at higher risk for transfusion-related complications (Evidence: Expert opinion 3).

References

1 Sadhewa A, Satyagraha AW, Alam MS, Adissu W, Anvikar A, Bancone G et al.. Performance of quantitative point-of-care tests to measure G6PD activity: An individual participant data meta-analysis. PLoS neglected tropical diseases 2025. link 2 Lo YH, Mok KL. High dose vitamin C induced methemoglobinemia and hemolytic anemia in glucose-6-phosphate dehydrogenase deficiency. The American journal of emergency medicine 2020. link 3 Francis RO, Jhang JS, Pham HP, Hod EA, Zimring JC, Spitalnik SL. Glucose-6-phosphate dehydrogenase deficiency in transfusion medicine: the unknown risks. Vox sanguinis 2013. link 4 Livshits Z, Hoffman RS, Hymes KB, Nelson LS. If vitamins could kill: massive hemolysis following naturopathic vitamin infusion. Journal of medical toxicology : official journal of the American College of Medical Toxicology 2011. link 5 Chiang WL, Chu SC, Lai JC, Yang SF, Chiou HL, Hsieh YS. Alternations in quantities and activities of erythrocyte cytosolic carbonic anhydrase isoenzymes in glucose-6-phosphate dehydrogenase-deficient individuals. Clinica chimica acta; international journal of clinical chemistry 2001. link00682-9) 6 Cummings AM, Barker KL. Isolation of a precursor and a nascent chain form of glucose-6-phosphate dehydrogenase from rat uterus and regulation of precursor processing by estradiol. Biochimica et biophysica acta 1986. link90084-x) 7 González R, Estrada M, García M, Gutierrez A. G6PD Ciudad de la Habana: a new slow variant with deficiency found in a Cuban family. Human genetics 1980. link 8 Gerli GC, Agostoni A, Fiorelli G. G-6PD loading of G-6PD-deficient erythrocytes. Experientia 1978. link 9 Richard F, Belhani M, Legay JM, Colonna P. Phenotypic variation in red cell G-6PD deficiency in heterozygotes. Biomedicine / [publiee pour l'A.A.I.C.I.G.] 1977. link

Deficiency of glucose-6-phosphate dehydrogenase