G6PD Variants and Haemolytic Sensitivity to Primaquine and Other Drugs

Abstract

Restrictions on the cultivation and ingestion of fava beans were first reported as early as the fifth century BC. Not until the late 19th century were clinical descriptions of fava-induced disease reported and soon after characterised as “favism” in the early 20th century. It is now well known that favism as well as drug-induced haemolysis is caused by a deficiency of the glucose-6-phosphate dehydrogenase (G6PD) enzyme, one of the most common enzyme deficiency in humans. Interest about the interaction between G6PD deficiency and therapeutics has increased recently because mass treatment with oxidative 8-aminoquinolines is necessary for malaria elimination. Historically, assessments of haemolytic risk have focused on the clinical outcomes (e.g., haemolysis) associated with either a simplified phenotypic G6PD characterisation (deficient or normal) or an ill-fitting classification of G6PD genetic variants. It is increasingly apparent that detailed knowledge of both aspects is required for a complete understanding of haemolytic risk. While more attention has been devoted recently to better phenotypic characterisation of G6PD activity (including the development of new point-of care tests), the classification of G6PD variants should be revised to be clinically useful in malaria eliminating countries and in populations with prevalent G6PD deficiency. The scope of this work is to summarize available literature on drug-induced haemolysis among individuals with different G6PD variants and to highlight knowledge gaps that could be filled with further clinical and laboratory research.

Prevalence of Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency among Malaria Patients in Southern Thailand: 8 Years Retrospective Study

“…The previous studies also identified G6PD Mahidol and Viangchan variants as the major variants among healthy individuals in southern Thailand [17,18]. These variants were also commonly present in neighboring countries, including Cambodia, Laos, Myanmar [23,42]. We detected a small portion of G6PD Kaiping (1,388G> A), Union (1,360C> T), and Mediterranean (563C> T).…”

Basic Research of Plasmodium vivax Biology Enabling Its Management as a Clinical and Public Health Problem

“…All of the variants are sensitive to 8aminoquinolines, with life threatening drug-induced severe acute haemolytic anaemia occurring even in patients with socalled mild variants (Pamba et al, 2012;Monteiro et al, 2016). The clinical complexity of the event in part explains the danger of oversimplified rules of thumb regarding this serious problem (Chu and Freedman, 2019;Bancone and Chu, 2021).…”

Cell and Gene Therapy for Anemia: Hematopoietic Stem Cells and Gene Editing

“…G6PD deficiency affects more than 400 million people worldwide [78][79][80]. A deficiency that occurs secondary to the mutation of the G6PD gene on the X chromosome was discovered in the 1950s, when American soldiers experienced acute hemolytic anemia due to antimalarial treatment; this deficiency is known as primaquine sensitivity syndrome [81,82].…”