Glucose-6-Phosphate Dehydrogenase Deficiency - The Most Common Enzyme Disorder and Its Links to Anemia, Jaundice, and Malaria

Glucose-6-phosphate dehydrogenase deficiency is the most common enzyme disorder in humans. The life-long genetic disorder is highly common in malaria-endemic areas, yet it can make malaria treatment deadly. Should testing for a disorder so prevalent be a standard of antenatal care? 

In 1989, the World Health Organization stated that Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme disorder in humans, affecting approximately 400 million people around the globe. As G6PD deficiency is an X-linked disorder, the disorder affects mostly males. However, G6PD deficiency also affects a large number of females due to the high prevalence of the gene in malaria-endemic areas. G6PD deficiency is most common in malaria-endemic areas, which in some areas can affect over 20% of the population. These areas include Sub-Saharan Africa, the Middle East, the Mediterranean, and parts of southern Asia. Glucose-6-phosphate dehydrogenase deficiency can cause hemolytic anemia and is often responsible for neonatal jaundice, a condition that can cause brain damage, death, and or other disorders and complications. 

Glucose-6-phosphate dehydrogenase deficiency is an X-linked disorder that results in abnormally low levels of Glucose-6-phosphate dehydrogenase, an enzyme that is important to glycolysis and the protection of red blood cells from oxidative damage. Glycolysis is the breakdown of glucose (C6H12O6), an important source of energy in humans, into usable energy for the body. In the absence of Glucose-6-phosphate dehydrogenase, more red blood cells may be destroyed than are produced, causing hemolytic anemia. 

When hemolytic anemia is left untreated, a person may develop heart arrhythmias, cardiomyopathy, and heart failure. Acute hemolytic crises can occur in people with G6PD deficiency due to interactions with certain drugs and fava beans, infections, diabetic ketoacidosis, and spontaneously in neonates and may lead to acute renal failure and or death. 

Glucose-6-phosphate dehydrogenase deficiency may also cause neonatal jaundice. Neonatal jaundice, or neonatal hyperbilirubinemia, is a condition caused by excess bilirubin in the body. Bilirubin is a pigment that is released when red blood cells are destroyed, which can be harmful to the body in excess. Hence, the destruction of red blood cells and hemolytic anemia due to G6PD deficiency may cause neonatal jaundice. When left untreated, neonatal jaundice can cause hemorrhage, sepsis, infection, liver malfunction, spastic cerebral palsy, kernicterus, and biliary atresia (Mayo Clinic, 2020), disorders that can lead to brain damage, organ damage, and death. Neonatal jaundice can be easily and inexpensively treated with phototherapy. 

In pregnancy, women with G6PD deficiency experience a higher rate of spontaneous abortions and low erythrocyte counts during puerperal period than in women that are not G6PD deficient. Infants born to G6PD deficient mothers often have lower birth weights than those of non-G6PD deficient mothers. 

While many people that carry the gene for G6PD deficiency are asymptomatic, G6PD deficiency is a serious health concern for many, especially in malaria-endemic areas. Infection with malaria is complicated by G6PD deficiency, as people affected by the deficiency may have a life-threatening hemolytic crisis in reaction to drugs used in malaria treatment. People with G6PD deficiency may also experience hemolytic crises in reaction to other drugs such as sulphonamides, sulphones, and antibacterial compounds and fava beans. 

Many studies suggest that males with G6PD deficiency have higher immunity against Plasmodium falciparum malaria than those without G6PD deficiency, which lends itself to the high prevalence of genetic G6PD deficiency in areas where malaria is common or was previously common. 

Glucose-6-phosphate dehydrogenase deficiency is a major public health concern globally. Accessibility to information and testing for Glucose-6-phosphate dehydrogenase deficiency is crucial to the health and livelihood of people all over the world, but especially in malaria-endemic areas. G6PD deficiency screening of neonates and education of parents and guardians of G6PD deficiency and the dangers of neonatal jaundice has been found effective to prevent hemolytic crises from drug and fava bean interactions and kernicterus from untreated hyperbilirubinemia. Guardians of a child with G6PD deficient infants must be mindful of the drugs and food the child consumes and parents that breastfeed infants with G6PD deficiency should avoid ingestion of fava beans or drugs that could harm the child. Likewise, it is important for individuals to know if they are G6PD deficient. 

By Julia Doo, longtime collaborator and researcher with Maternova and with Meg Wirth, Founder

Sources

Beutler, E. (2001). Glucose-6-phosphate dehydrogenase deficiency and other red cell enzyme abnormalities. Williams Hematology, 6th edition. New York: McGraw-Hill, 527-545.

Guindo, A., Fairhurst, R. M., Doumbo, O. K., Wellems, T. E., & Diallo, D. A. (2007). X-linked G6PD deficiency protects hemizygous males but not heterozygous females against severe malaria. PLoS medicine, 4(3), e66.

Kaplan, M., & Hammerman, C. (2009). The need for neonatal glucose-6-phosphate dehydrogenase screening: a global perspective. Journal of Perinatology, 29(1), S46-S52.

Mayo Clinic. (2020). Infant jaundice. Diseases & Conditions. 

National Institutes of Health: National Heart, Lung, and Blood Institute. (2019). Hemolytic Anemia. Health Topics. 

National Organization for Rare Disorders. (2017). Glucose-6-Phosphate Dehydrogenase Deficiency. Rare Disease Database.  

Nkhoma, E. T., Poole, C., Vannappagari, V., Hall, S. A., & Beutler, E. (2009). The global prevalence of glucose-6-phosphate dehydrogenase deficiency: A systematic review and meta-analysis. Blood Cells, Molecules, and Diseases, 42(3), 267–278. doi:10.1016/j.bcmd.2008.12.005

Perkins, R. P. (1976). The significance of glucose-6-phosphate dehydrogenase deficiency in pregnancy. American journal of obstetrics and gynecology, 125(2), 215-223.

WHO Working Group. (1989). Glucose-6-phosphate dehydrogenase deficiency. Bulletin of the World Health Organization, 67(6), 601–611. 

Photograph:

Unique Identifier: UN7758687
Headline: UN Mission Gives Medical Treatment in Liberia
Caption Description: Medical staff of the Chinese Contingent of the United Nations Mission in Liberia
(UNMIL) perform an ultra-sound in their clinic, open to all national citizens in their area of operation in
Zwedru, Liberia.
Country: Liberia
Production Date: 4/23/2005 7:49:05 PM