Glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency)

G6PD deficiency is the most common enzyme defect in humans. It is caused by a deficiency of glucose-6-phosphate dehydrogenase, an enzyme present in red blood cells. The most frequent symptoms are jaundice and hemolytic anemia.

Glucose-6-phosphate dehydrogenase or G6PD is an enzyme involved in a mitochondria-independent metabolic pathway that produces energy in the form of NADPH. Since red blood cells or erythrocytes do not have mitochondria, this metabolic pathway is of great importance for these blood cells as the only source of energy.

The presence of pathogenic variants in the G6PD gene results in the production of an enzyme with reduced activity which affects the erythrocytes and manifests itself in the form of hemolytic anemia and jaundice (yellowing of the skin, mucous membranes or eyes), especially when there is an external triggering agent. G6PD deficiency is a pathology that is inherited from the mothers as the G6PD gene is located on the X chromosome.

The global distribution of G6PD deficiency is similar to that of malaria, suggesting that G6PD deficiency confers protection against infection. G6PD deficiency is most prevalent in Africa, Asia, the Mediterranean region and the Middle East. However, due to migration, it has spread to the Americas and Europe.

Symptoms

When oxidative stress occurs in red blood cells, if there is a deficiency in G6PD and, therefore, a reduction in NADPH levels, the reactions that facilitate the elimination of the substances that produce this stress (superoxide anion and hydrogen peroxide) are inhibited, so that they accumulate and destroy the red blood cells, causing hemolytic anemia.The reactions that facilitate the elimination of the substances that produce this stress (superoxide anion and hydrogen peroxide) are inhibited so that they accumulate and destroy the red blood cells, causing hemolytic anemia.

Patients with glucose-6-phosphate dehydrogenase deficiency are more likely to develop acute hemolytic anemia after taking certain medications, for example, some antibiotics such as erythromycin and drugs used to treat malaria such as primaquine. Hemolytic anemia is also triggered by eating fava beans (vicia faba). This reaction is known as fabism and can be very severe in some cases even requiring transfusions.

Disease management

Fabismus, which is the acute reaction produced by consumption of beans in people with G6PD deficiency, can be avoided, especially in children, by knowing their status and avoiding consumption of these legumes.

Current WHO guidelines recommend that people with malaria should be screened for G6PD deficiency before starting primaquine treatment, so that people at higher risk of hemolysis can receive alternative treatment.

Genes analyzed

G6PD

Bibliography

Cappellini MD, Fiorelli G. Glucose-6-phosphate dehydrogenase deficiency. Lancet. 2008 Jan 5;371(9606):64-74.

Zhong Z, Wu H, Li B, et al . Analysis of Glucose-6-Phosphate Dehydrogenase Genetic Polymorphism in the Hakka Population in Southern China. Med Sci Monit. 2018 Oct 13;24:7316-7321.

Kashmoola MA, Eissa AA, Al-Takay DT, Al-Allawi NA. Molecular Characterization of G6PD Deficient Variants in Nineveh Province, Northwestern Iraq. Indian J Hematol Blood Transfus. 2015 Mar;31(1):133-6.

Luzzatto L, Arese P . Favism and Glucose-6-Phosphate Dehydrogenase Deficiency. N Engl J Med. 2018 Jan 4;378(1):60-71.

Manjurano A, Clark TG, Nadjm B, et al . Candidate human genetic polymorphisms and severe malaria in a Tanzanian population. PLoS One. 2012;7(10):e47463.

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