G6PD Deficiency
A silent killer that can cause organ failure, but is easily managed.
Glucose-6-Phosphate-Dehydrogenase Deficiency (G-6-PD) is a genetic deficiency that causes red blood cells to hemolyze in the presence of certain drugs or chemicals, infections or other stressors. Statistically determined to affect more than four hundred million people globally, mostly people of South Asia, Middle East and sub-Saharan African descent. When triggered, symptoms include fever, dark colored urine, abdominal and back pain, fatigue, and pale skin.
The image shows global distribution of G6PD deficiency genes. The darker colors indicate regions of high prevalence. Don’t be fooled by the totally white regions because they are now homes to people from the regions of high deficiency.
G-6-PD (also G6PD) deficiency is a result of G6PD gene mutation. The gene provides instructions for making an enzyme called glucose-6-phosphate dehydrogenase. The enzyme (aka as G6PDH) is a cytosolic enzyme that catalyzes the chemical reaction
D-glucose 6-phosphate + NA dP+<----> 6-phosphate-D-glucano-1,5-lactone + NA dP H + H+
The enzyme participates in the pentose phosphate pathway, which is a metabolic pathway that supplies reducing energy to cells, such a erythrocytes, by maintaining the levels of the coenzyme nicotinamide adenine dinucleotide phosphate (NADPH). The NADPH the maintains the level of glutathione in these cells that help protect the red blood cells against oxidative damage from compounds like hydrogen peroxide.
The G6PDH enzyme is active in virtually all cell types and is involved in the normal processing of carbohydrates. It plays a critical role in red blood cells as described above. It helps protect red blood from premature destruction (hemolysis). It is responsible for the first step in the pentose phosphate pathway, a series of chemical reactions that convert glucose to another sugar, ribose-5-phosphate. Ribose-5-phosphate is an important component of nucleotides, which are the building blocks of DNA and it’s chemical cousin RNA. The chemical reaction produces NADPH as shown above, which plays a role in protecting cells from potentially harmful molecules called reactive oxygen species. These molecules are by products of normal cellular functions. Reactions involving NADPH produces compounds that prevent reactive oxygen species from building up to toxic levels within cells. The production of NADPH by G6PD is essential in red blood cells, which are particularly susceptible to damage by reactive oxygen species because they lack other NADPH-producing enzymes.
More than 200 mutations that cause glucose-6-phosphate dehydrogenase deficiency have been identified in the G6PD gene. Almost all these mutations lead to changes in single building blocks (amino acids) in the glucose-6-phosphate dehydrogenase enzyme. These changes disrupt normal structure and functions of the enzyme or reduce the amount of the enzyme produced in cells.
Without enough functional glucose-6-phosphate dehydrogenase, red blood cells are unable to protect themselves from the damaging effects of reactive species. The damaged cells are likely to rupture and break down prematurely (undergoing hemolysis). Factors such as infections, certain drugs, and ingesting fava beans can increase the levels of reactive oxygen species, causing red blood cells to hemolyze faster than they can be replaced by the body. Primary symptom of this condition is hemolytic anemia.
The gene is in the X chromosome. The deficiency is more common among men because men have one X chromosome inherited from their mother, while women have two, one from each parent. (The likelihood of both parents presenting bad X chromosomes is quit low). It is located in Xq28as shown above. The G6PD deficiency may cause neonatal jaundice, acute hemolysis, or severe and chronic non spherocytic hemolytic anemia. In rare cases, it may result in acute renal failure.
Women however do suffer from G6PD deficiency and their level of disease severity depends partly on if one X chromosome is affected or if it is both. Women with both X chromosomes being affected will generally pass it on to all their offsprings, while women with one affected X can pass it on to just some of their offsprings. Also, women with one affected X chromosome may never exhibit any disease signature.
G6PD deficiency is not all bad, actually the predominance in certain region (so call Malaria region) is the result of natural selection. Deficiency has also been associated with reduction in the risk of colorectal cancer1
2Uncited Reference : G6PD Deficiency Prevalence and Estimates of Affected Populations in Malaria Endemic Countries