Glucose-6-phosphate dehydrogenase deficiency
382801
225930151
2008-07-16T01:55:48Z
Sephiroth BCR
621952
Reverted edits by [[Special:Contributions/67.70.196.236|67.70.196.236]] to last version by Sephiroth BCR (using [[WP:HG|Huggle]])
{{DiseaseDisorder infobox |
Name = Glucose-6-phosphate dehydrogenase deficiency |
Image = G6PD - 3D structure - PDB1qki.png |
Caption = [[Glucose-6-phosphate dehydrogenase]] |
ICD10 = {{ICD10|D|55|0|d|55}} |
ICD9 = {{ICD9|282.2}} |
ICDO = |
OMIM = 305900 |
DiseasesDB = 5037 |
MedlinePlus = 000528 |
eMedicineSubj = med |
eMedicineTopic = 900 |
MeshID = D005955 |
}}
'''Glucose-6-phosphate dehydrogenase deficiency''' is an [[Sex-linked|X-linked recessive]] [[hereditary disease]] characterised by abnormally low levels of the [[glucose-6-phosphate dehydrogenase]] enzyme (abbreviated '''G6PD''' or '''G6PDH'''). It is a metabolic enzyme involved in the [[pentose phosphate pathway]], especially important in [[red blood cell]] metabolism. Individuals with the disease may exhibit nonimmune [[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.
== Signs and symptoms ==
Patients are almost exclusively male, due to the [[X-linked]] pattern of inheritance, but female carriers can be clinically affected due to [[lyonization]] where random inactivation of an X-chromosome in certain cells creates a population of [[G6PD]] deficient red cells coexisting with normal red cells. G6PD manifests itself in a number of ways:
* Prolonged [[neonatal jaundice]]
* [[Hemolysis|Hemolytic]] crises in response to:
** Certain [[medication|drugs]] (see below)
** Certain foods, most notably [[broad bean]]s
** Illness (severe infections)
** [[Diabetic ketoacidosis]]
* Very severe crises can cause [[acute renal failure]]
Favism is a disorder characterized by hemolytic anemia in response to ingestion of fava beans. Favism as a diagnosis has been known since antiquity, perhaps in relation to Pythagoras, among others (see Beutler review and below). All individuals with favism show G6PD deficiency. However, not all individuals with G6PD deficiency show favism. For example, in a small study of 757 Saudi men, more than 42% showed G6PD deficiency, but none reported symptoms of favism, despite fava in the diet.<ref>{{cite web |url=http://www.kfshrc.edu.sa/annals/166/95-371.html |title=Common G6PD variant from Saudi population |accessdate=2007-10-28 |format= |work=}}</ref> Favism is known to be more prevalent in infants and children, and G6PD genetic variant can influence chemical sensitivity. Other than this, the detailed chemical relationship between favism and G6PD is not well known.
Below is a list of things that can be harmful in people with G6PD deficiency.
Antimalarials:
* Primaquine
* Pamaquine
* Chloroquine
Analgesics (which contain aspirin or phenacetin):
* Aspirin
* Bufferin
* Anacin
* Excedrin
* Empirin
* APC Tablets
* Darvon Compound
* Coricidin
Antibiotics:
* Sulfanilamide
* Sulfapyridine
* Sulfadimidine
* Sulfacetamide
* Glucosulfone sodium
* Nitrofurantoin
* Furazolidone
* Nitrofurazone
* Dapsone
* Sulfoxone
* Sulfisoxazole
Anthelmintics:
* B-Naphthol
* Stibophen
* Niridazole
Miscellaneous:
* Probenecid
* Thiazide Diuretics
* Phenothiazine
* Chloramphenicol
* Orinase
* Dimercaprol
* Methylene blue
* Naphthalene (moth balls)
* Vitamin K
* [[Fava beans]] (Also, bell beans, broad beans, English dwarf beans, fever beans, haba beans, horse beans, lima beans, pigeon beans, silkworm beans, tick beans)
* [[Henna]] can cause a haemolytic crisis in G6PD deficient infants.<ref>{{cite journal |author=Raupp P, Hassan JA, Varughese M, Kristiansson B |title=Henna causes life threatening haemolysis in glucose-6-phosphate dehydrogenase deficiency |journal=Arch. Dis. Child. |volume=85 |issue=5 |pages=411–2 |year=2001 |pmid=11668106|doi=10.1136/adc.85.5.411}}</ref>
==Diagnosis==
The diagnosis is generally suspected when patients from certain ethnic groups (see below) develop [[anemia]], [[jaundice]] and symptoms of [[hemolysis]] after challenge to any of the above causes, especially when there is a positive family history.
Generally, tests will include:
* [[Complete blood count]] and [[reticulocyte]] count; in active G6PD, [[Heinz body|Heinz bodies]] can be seen in [[red blood cell]]s on a [[blood film]];
* [[Liver enzyme]]s (to exclude other causes of [[jaundice]]);
* [[Lactate dehydrogenase]] (elevated in hemolysis and a marker of its severity)
* [[Haptoglobin]] (decreased in hemolysis);
* A "[[Coombs test|direct antiglobulin test]]" (Coombs' test) - this should be negative, as [[hemolysis]] in G6PD is not immune-mediated;
* [[Thyroid-stimulating hormone|TSH]] measurement.
When there are sufficient grounds to suspect G6PD, a direct test for G6PD is the "Beutler fluorescent spot test", which has largely replaced an older test (the Motulsky dye-decolouration test). Other possibilities are direct DNA testing and/or sequencing of the G6PD gene.
The ''Beutler fluorescent spot test'' is a rapid and inexpensive test that visually identifies [[Nicotinamide adenine dinucleotide phosphate|NADPH]] produced by G6PD under [[ultraviolet light]]. When the blood spot does not fluoresce, the test is positive; it can be falsely negative in patients who are actively hemolysing. It can therefore only be done 2-3 weeks after a hemolytic episode.
When a macrophage in the spleen "sees" an RBC with a Heinz body, it removes the precipitate and a small piece of the membrane, leading to characteristic "bite cells". However, if a large number of Heinz bodies are produced, as in the case of G6PD deficiency, some Heinz bodies will nonetheless be visible when viewing RBCs that have been stained with crystal violet. This easy and inexpensive test can lead to an initial presumption of G6PD deficiency, which can be confirmed with the other tests.
==Classification==
There are four forms of G6PD:
# Hereditary nonspherocytic hemolytic anemia
# Severe deficiency
# Mild deficiency
# Non-deficient variant
==Pathophysiology==
[[image:G6PD_mechanism.png|450px|right|Mechanism of G6PD]]
Glucose-6-phosphate dehydrogenase (G6PD) is an [[enzyme]] in the [[pentose phosphate pathway]] (see image), 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]].{{Fact|date=February 2007}}
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).
==Epidemiology==
G6PDH is said to be the most common enzyme deficiency disease in the world, affecting approximately 400,000,000 people globally. African, Middle Eastern and South Asian people are affected the most along with those who are mixed with any of the above. <ref>[http://www.rddiagnostics.com/g6pd_faq.htm G-6-PD FAQ section<!-- Bot generated title -->]</ref> A side effect of this disease is that it confers protection against [[malaria]], in particular the form of malaria caused by ''[[Plasmodium falciparum]]'', the most deadly form of malaria. A similar relationship exists between malaria and [[sickle-cell disease]]. An explanation is that cells infected with the ''Plasmodium'' parasite are cleared more rapidly by the [[spleen]]. This phenomenon might give G6PDH deficiency carriers an evolutionary advantage.
==Treatment==
The most important measure is prevention - avoidance of the drugs and foods that cause hemolysis. [[Vaccination]] against some common pathogens (e.g. [[hepatitis A]]) may prevent infection-induced attacks.
In the acute phase of hemolysis, [[blood transfusion]]s might be necessary, or even [[dialysis]] in [[acute renal failure]]. Blood transfusion is an important symptomatic measure, as the transfused red cells are generally not G6PD deficient.
Some patients benefit from removal of the [[spleen]] ([[splenectomy]]), as this is an important site of red cell destruction. [[Folic acid]] should be used in any disorder featuring a high red cell turnover. Although [[vitamin E]] and [[selenium]] have antioxidant properties, their use does not decrease the severity of G6PD.
==Pythagorean teachings==
One theory for the [[Pythagoreanism|Pythagoreans']] avoidance of beans is avoidance of favism, but more likely, this was a philosophical matter, such as the belief that beans and humans were created from the same material.<ref>Gabrielle Hatfield, ''review'' of Frederick J. Simoons, ''Plants of Life, Plants of Death'', University of Wisconsin Press, 1999. ISBN 0-299-15904-3. In ''Folklore'' '''111''':317-318 (2000). [http://links.jstor.org/sici?sici=0015-587X%28200010%29111%3A2%3C317%3APOLPOD%3E2.0.CO%3B2-A at JSTOR]</ref><ref>{{cite book |author=Rendall, Steven; Riedweg, Christoph |title=Pythagoras: his life, teaching, and influence |publisher=Cornell University Press |location=Ithaca, N.Y |year=2005 |pages= |isbn=0-8014-4240-0 |oclc= |doi=}}</ref>
==References==
* {{cite journal |author=Beutler E |title=G6PD deficiency |journal=Blood |volume=84 |issue=11 |pages=3613–36 |year=1994 |pmid=7949118 |doi=}}
* {{cite journal |author=Mehta A, Mason PJ, Vulliamy TJ |title=Glucose-6-phosphate dehydrogenase deficiency |journal=Baillieres Best Pract. Res. Clin. Haematol. |volume=13 |issue=1 |pages=21–38 |year=2000 |pmid=10916676 |doi=}}
<references/>
==External links==
*[http://www.rialto.com/g6pd/ The G6PD homepage]
*[http://www.g6pd.org/ G6PD Deficiency Association]
*[http://www.rddiagnostics.com/g6pd_faq.htm A FAQ page on G6PD Deficiency by R&D Diagnostics]
*[http://www.fpnotebook.com/HEM203.htm Family Practice Notebook/G6PD Deficiency (Favism)]
{{Hematology}}
{{Inborn errors of carbohydrate metabolism}}
[[Category:Hematology]]
[[bn:গ্লুকোজ-৬-ফসফেট ডিহাইড্রোজেনেজ স্বল্পতা]]
[[bg:Глюкозо-6-фосфатдехидрогеназна недостатъчност]]
[[de:G6PD-Mangel]]
[[es:Deficiencia de glucosa-6-fosfato deshidrogenasa]]
[[fr:Déficit en glucose-6-phosphate déshydrogénase]]
[[hr:Manjak enzima glukoza-6-fosfat dehidrogenaze]]
[[it:Favismo]]
[[he:חוסר G6PD]]
[[ja:ソラマメ中毒]]
[[pl:Niedobór dehydrogenazy glukozo-6-fosforanowej]]
[[pt:Deficiência em glucose-6-fosfato desidrogenase]]
[[simple:Favism]]
[[th:โรคพร่องเอนไซม์ G-6-PD]]
[[zh:葡萄糖六磷酸鹽脫氫酶缺乏症]]