Glucose-6-phosphate dehydrogenase deficiency pathophysiology: Difference between revisions
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'''Glucose-6-phosphate dehydrogenase (G6PD) deficiency''' is an [[Sex-linked|X-linked recessive]] [[hereditary disease]] featuring abnormally low levels of the [[G6PD]] enzyme, which plays an important role in [[red blood cell]] function. Individuals with the disease may exhibit non-immune [[hemolytic anemia]] in response to a number of causes. It is closely linked to '''[[favism]]''', a disorder characterized by a hemolytic reaction to consumption of [[Vicia faba|broad bean]]s, with a name derived from the [[Italian language|Italian]] name of the broad bean (''fava''). Sometimes the name, [[favism]], is alternatively used to refer to the enzyme | '''Glucose-6-phosphate dehydrogenase (G6PD) deficiency''' is an [[Sex-linked|X-linked recessive]] [[hereditary disease]] featuring abnormally low levels of the [[G6PD]] enzyme, which plays an important role in [[red blood cell]] function. Individuals with the disease may exhibit non-immune [[hemolytic anemia]] in response to a number of causes. It is closely linked to '''[[favism]]''', a disorder characterized by a hemolytic reaction to consumption of [[Vicia faba|broad bean]]s, with a name derived from the [[Italian language|Italian]] name of the broad bean (''fava''). Sometimes the name, [[favism]], is alternatively used to refer to the enzyme | ||
deficiency as a whole. | deficiency as a whole. | ||
==Pathophysiology== | |||
* [[Glucose-6-phosphate dehydrogenase]] ([[G6PD]]) is an [[enzyme]] in the [[pentose phosphate pathway]], a [[metabolic pathway]] that supplies reducing energy to cells (most notably [[erythrocyte]]s) by maintaining the level of the [[co-enzyme]] [[nicotinamide adenine dinucleotide phosphate|nicotinamide adenine dinucleotide phosphate]] (NADPH). | |||
* The NADPH in turn maintains the level of [[glutathione]] in these cells that helps protect the red blood cells against [[oxidation|oxidative]] damage. G6PD converts [[glucose-6-phosphate]] into [[6-phosphoglucono-δ-lactone]] and is the rate-limiting enzyme of the ''pentose phosphate pathway''. | |||
* Patients with [[G6PD deficiency]] are at risk of [[hemolytic anemia]] in states of [[oxidative stress]]. This can be in severe infection, [[medication]] and certain foods. [[Broad bean]]s contain high levels of vicine, divicine, convicine and isouramil — all are [[oxidant]]s. | |||
* In states of oxidative stress, all remaining [[glutathione]] is consumed. Enzymes and other proteins (including [[hemoglobin]]) are subsequently damaged by the oxidants, leading to [[electrolyte]] imbalance, membrane cross-bonding and [[phagocytosis]] and [[spleen|splenic]] sequestration of red blood cells. The hemoglobin is metabolized to [[bilirubin]] (causing [[jaundice]] at high concentrations) or excreted directly by the [[kidney]] (causing [[acute renal failure]] in severe cases). | |||
* Deficiency of G6PD in the alternative pathway causes the build up of glucose and thus there is an increase of [[advanced glycation endproduct]]s (AGE). The deficiency also causes a reduction of NADPH which is necessary for the formation of Nitric Oxide (NO). The high prevalence of [[diabetes mellitus type 2]] and [[hypertension]] in Afro-Caribbeans in the West could be directly related to G6PD deficiency.<ref>{{cite journal |author=Gaskin RS, Estwick D, Peddi R |title=G6PD deficiency: its role in the high prevalence of hypertension and diabetes mellitus |journal=Ethnicity & disease |volume=11 |issue=4 |pages=749–54 |year=2001 |pmid=11763298 |doi=}}</ref> | |||
* Some other epidemiological reports have pointed out, however, that G6PD seems to decrease the susceptibility to [[cancer]], [[cardiovascular disease]] and [[stroke]]. | |||
* Although female carriers can have a mild form of G6PD deficiency (dependent on the degree of inactivation of the unaffected X chromosome - see ''[[lyonization]]''), homozygous females have been described; in these females there is co-incidence of a [[rare disease|rare]] [[immunology|immune disorder]] termed [[chronic granulomatous disease]] (CGD). | |||
[[image:G6PD_mechanism.png|550px|left|Mechanism of G6PD]] | |||
<br clear="center"/> | |||
==References== | ==References== | ||
{{reflist|2}} | {{reflist|2}} | ||
Revision as of 18:11, 21 September 2012
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Priyamvada Singh, M.D. [2]
Overview
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive hereditary disease featuring abnormally low levels of the G6PD enzyme, which plays an important role in red blood cell function. Individuals with the disease may exhibit non-immune hemolytic anemia in response to a number of causes. It is closely linked to favism, a disorder characterized by a hemolytic reaction to consumption of broad beans, with a name derived from the Italian name of the broad bean (fava). Sometimes the name, favism, is alternatively used to refer to the enzyme deficiency as a whole.
Pathophysiology
- Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme in the pentose phosphate pathway, a metabolic pathway that supplies reducing energy to cells (most notably erythrocytes) by maintaining the level of the co-enzyme nicotinamide adenine dinucleotide phosphate (NADPH).
- The NADPH in turn maintains the level of glutathione in these cells that helps protect the red blood cells against oxidative damage. G6PD converts glucose-6-phosphate into 6-phosphoglucono-δ-lactone and is the rate-limiting enzyme of the pentose phosphate pathway.
- Patients with G6PD deficiency are at risk of hemolytic anemia in states of oxidative stress. This can be in severe infection, medication and certain foods. Broad beans contain high levels of vicine, divicine, convicine and isouramil — all are oxidants.
- In states of oxidative stress, all remaining glutathione is consumed. Enzymes and other proteins (including hemoglobin) are subsequently damaged by the oxidants, leading to electrolyte imbalance, membrane cross-bonding and phagocytosis and splenic sequestration of red blood cells. The hemoglobin is metabolized to bilirubin (causing jaundice at high concentrations) or excreted directly by the kidney (causing acute renal failure in severe cases).
- Deficiency of G6PD in the alternative pathway causes the build up of glucose and thus there is an increase of advanced glycation endproducts (AGE). The deficiency also causes a reduction of NADPH which is necessary for the formation of Nitric Oxide (NO). The high prevalence of diabetes mellitus type 2 and hypertension in Afro-Caribbeans in the West could be directly related to G6PD deficiency.[1]
- Some other epidemiological reports have pointed out, however, that G6PD seems to decrease the susceptibility to cancer, cardiovascular disease and stroke.
- Although female carriers can have a mild form of G6PD deficiency (dependent on the degree of inactivation of the unaffected X chromosome - see lyonization), homozygous females have been described; in these females there is co-incidence of a rare immune disorder termed chronic granulomatous disease (CGD).
