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pathophysiology-of-g6pd-deficiency


Epidemiology of G6PD Deficiency

G6PD deficiency is more common in people from the Mediterranean and Africa. Patients need to avoid factors that lead to the production of excess oxidants; these factors include some drugs and kidney beans.

Etiology and Pathogenesis of G6PD Deficiency

G6PD is caused by a point mutation or a deletion in the glucose-6-phosphate-dehydrogenase gene. It is an X-linked disease. Usually, women are carriers, while men are diseased.

The mutation decreases the half-life of the enzyme (t1/2 = 13 days, normal 62). The absence or lack of G6PD in the erythrocytes leads to production disorders of NADPH. Without sufficient NADPH, the erythrocytes lack protection from oxidation. As a consequence, they are prematurely degraded and hemolysis occurs.

Biochemistry of G6PD deficiency

biochemistry-of-g6pd-deficiency

Image: Biochemistry of G6PD deficiency. By Lecturio

Clinical Features of G6PD Deficiency

The clinical picture of G6PD is not clear and mainly depends on the degree of the enzymatic defect or deficiency. While some patients do not show any or only slight discomfort, others suffer from partially severe hemolytic crises with severe pain in the abdominal and back area. Moreover, fever and rigor are possible.

If infants suffer from the enzyme deficiency, they often show neonatal jaundice due to impaired liver function.

Neonatal jaundice

Image: Newborn infant undergoing phototherapy to treat neonatal jaundice. By Martin Pot, License: CC-BY 3.0

Since the erythrocyte possesses decreased or no protection against oxidation in G6PD deficiency, increased oxidative stress can quickly lead to hemolytic crises. The consumption of fava beans can break through the existing protective barrier against highly oxidative substances, which is why the disease has the epithet favism. Oxidative stress-triggering factors include acute infections, medications such as sulfonamides, ASA, vitamin K analogs, analgesics, and antibiotics.

heinz_bodies_cat

Image: Heinz body stain of feline blood, showing 3 distinct Heinz bodies. By Ailuromancy, License: Public domain

The pentose phosphate pathway is the only source of NADPH in RBCs. NADPH is required for the recycling of glutathione. Glutathione repairs oxidative damage. G6PD deficiency leads to oxidative damage, including hemoglobin precipitation (Heinz bodies) and membrane damage (bite cells). Heinz bodies are denatured hemoglobin. Bite cells are RBCs with membrane damage, partially consumed by macrophages. The damaged RBCs are cleared in the spleen (bite cells).

pathophysiology-of-g6pd-deficiency

Image: Pathophysiology of G6PD deficiency. By Lecturio

G6PD deficiency is most common in patients of African and Mediterranean descent. It causes episodic hemolytic anemia (pallor, fatigue, and jaundice) due to oxidative stress-triggering factors such as infection, oxidizing drugs (sulfonamides, nitrofurans, and antimalarials), and fava beans.

Diagnosis of G6PD Deficiency

g6pd_-_3d_structure

Image: Three-dimensional structure of protein/enzyme glucose-6-phosphate dehydrogenase (G6PD) derived from PDB-Datafile. By Christaras A (copier). Original Author is Jfdwolff, License: CC BY-SA 3.0

Since the blood count between the individual hemolytic crises can be inconspicuous, further tests for a definitive diagnosis are necessary. The detection of decreased or absent G6PD activity is diagnostic, preferably via a direct enzyme assay. Since contracted and fragmented cells can be seen in the blood smear during a crisis (bite cells and vesicular cells), this can also be used for diagnosis. Finally, Heinz bodies in the erythrocytes can be seen in the blood smear with a supravital stain out of oxidized, denatured hemoglobin.

Therapy for G6PD Deficiency

A possible, already existing medication should be checked for tolerance. If acute infection is present, it has to be treated. In severe cases, blood transfusion can be performed. Infants with neonatal jaundice could receive phototherapy and exchange transfusions.

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