|
|
| (35 intermediate revisions by 2 users not shown) |
| Line 13: |
Line 13: |
| MeshID = D005955 | | | MeshID = D005955 | |
| }} | | }} |
| {{SI}} | | {{Glucose-6-phosphate dehydrogenase deficiency}} |
| {{CMG}}; '''Associate Editor(s)-In-Chief:''' [[Priyamvada Singh|Priyamvada Singh, M.D.]] [mailto:psingh@perfuse.org] | | {{CMG}}; '''Associate Editor(s)-In-Chief:''' [[Priyamvada Singh|Priyamvada Singh, M.D.]] [mailto:psingh13579@gmail.com] |
|
| |
|
| ==Overview== | | ==[[Glucose-6-phosphate dehydrogenase deficiency overview|Overview]]== |
| '''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.
| |
|
| |
|
| ==Epidemiology and Demographics== | | ==[[Glucose-6-phosphate dehydrogenase deficiency historical perspective|Historical Perspective]]== |
| * G6PDD is said to be the most common enzyme deficiency disease in the world, affecting approximately 400,000,000 people globally.<ref>http://www.rddiagnostics.com/g6pd_faq.htm</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 [[G6PD deficiency]] carriers an evolutionary advantage.
| |
|
| |
|
| ==Classification== | | ==[[Glucose-6-phosphate dehydrogenase deficiency classification|Classification]]== |
| There are four forms of [[G6PD]]:
| |
| # [[Hereditary nonspherocytic hemolytic anemia]]
| |
| # Severe deficiency
| |
| # Mild deficiency
| |
| # Non-deficient variant
| |
| # [[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. 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.
| |
|
| |
|
| ==Pathophysiology== | | ==[[Glucose-6-phosphate dehydrogenase deficiency pathophysiology|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).
| | ==[[Glucose-6-phosphate dehydrogenase deficiency causes|Causes]]== |
| * 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]] | | ==[[Glucose-6-phosphate dehydrogenase deficiency differential diagnosis|Differentiating Glucose-6-phosphate dehydrogenase deficiency from other Diseases]]== |
| <br clear="center"/>
| |
|
| |
|
| | ==[[Glucose-6-phosphate dehydrogenase deficiency epidemiology and demographics|Epidemiology and Demographics]]== |
|
| |
|
| | ==[[Glucose-6-phosphate dehydrogenase deficiency risk factors|Risk Factors]]== |
|
| |
|
| | ==[[Glucose-6-phosphate dehydrogenase deficiency screening|Screening]]== |
|
| |
|
| | | ==[[Glucose-6-phosphate dehydrogenase deficiency natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
| | |
| | |
| | |
| | |
| | |
| | |
| | |
| | |
| | |
| | |
| | |
| | |
| | |
| | |
| | |
| | |
| | |
| | |
| | |
| | |
| | |
| | |
| ==History and Symptoms== | |
| ===History===
| |
| * 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.
| |
| * History of [[hemolysis|hemolytic]] crises in response to:
| |
| ** Certain [[medication|drugs]]:
| |
| *** [[Primaquine]] (an [[malaria|antimalarial]])
| |
| *** [[Sulphonamide]] [[antibiotic]]s
| |
| *** Sulphones (e.g. [[dapsone]], used against [[leprosy]])
| |
| *** Other sulphur-containing drugs: [[glibenclamide]] (an [[anti-diabetic drug]])
| |
| *** [[Nitrofurantoin]] (an [[antibiotic]] often used for [[urinary tract infection]]s)
| |
| *** [[Vitamin K]] analogues
| |
| *** Several others<ref>{{cite web |url=http://www.rialto.com/g6pd/table2.htm |title=The G6PD Deficiency Homepage -- Table 2 |accessdate=2007-10-28 |format= |work=}}</ref>
| |
| *** [[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=}}</ref>
| |
| ** Certain foods, most notably [[broad bean]]s
| |
| ** Illness (severe infections)
| |
| ** [[Diabetic ketoacidosis]]
| |
| | |
| ===Symptoms===
| |
| * Prolonged [[neonatal jaundice]]
| |
| * Hemolytic features like dark colored urine
| |
| * Very severe crises can cause [[acute renal failure]]
| |
|
| |
|
| ==Diagnosis== | | ==Diagnosis== |
| ===Laboratory diagnosis===
| |
| The diagnosis is generally suspected when patients from certain ethnic groups develop [[anemia]], [[jaundice]] and symptoms of [[hemolysis]] after challenge to any of the above causes, especially when there is a positive family history. At 2 to 4 days after introduction of the oxidative stress in patients with G6PD deficiency, onset of jaundice and dark urine occurs, with or without abdominal and back pain. The hemoglobin level decreases by 3 to 4 g/dL (30 to 40 g/L), and there is an appropriate increase in reticulocytes. The hemolysis spontaneously resolves in approximately 1 week as the older enzyme-depleted cells are replaced by new cells with sufficient G6PD to prevent further hemolysis. Additional laboratory findings in patients with G6PD deficiency include a negative direct and indirect antiglobulin (Coombs) test and the presence of "bite" or "blister" cells, produced when accumulated oxidized hemoglobin remains adherent to the erythrocyte membrane with an adjacent membrane-bound clear zone. Such cells are visible on this patient's peripheral blood smear. Because reticulocytes can have normal G6PD levels, measuring G6PD levels during an acute episode may produce a false-negative result.
| |
|
| |
|
| Generally, tests will include:
| | [[Glucose-6-phosphate dehydrogenase deficiency diagnostic study of choice|Diagnostic Study of Choice]] | [[Glucose-6-phosphate dehydrogenase deficiency history and symptoms|History and Symptoms]] | [[Glucose-6-phosphate dehydrogenase deficiency physical examination|Physical Examination]] | [[Glucose-6-phosphate dehydrogenase deficiency laboratory findings|Laboratory Findings]] | [[Glucose-6-phosphate dehydrogenase deficiency electrocardiogram|Electrocardiogram]] | [[Glucose-6-phosphate dehydrogenase deficiency chest x ray|Chest X Ray]] | [[Glucose-6-phosphate dehydrogenase deficiency CT|CT]] | [[Glucose-6-phosphate dehydrogenase deficiency MRI|MRI]] | [[Glucose-6-phosphate dehydrogenase deficiency echocardiography or ultrasound|Echocardiography or Ultrasound]] |
| * [[Complete blood count]]
| | | [[Glucose-6-phosphate dehydrogenase deficiency other imaging findings|Other Imaging Findings]] | [[Glucose-6-phosphate dehydrogenase deficiency other diagnostic studies|Other Diagnostic Studies]] |
| * [[Reticulocyte]] count
| |
| * [[Haptoglobin]] (decreased in hemolysis);
| |
| * A "[[Coombs test|direct antiglobulin test]]" (Coombs' test) - this should be negative, as [[hemolysis]] in G6PD is not immune-mediated;
| |
| * 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]])
| |
| * [[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.
| |
| ====Beutler fluorescent spot test: Late diagosis====
| |
| 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 false-positive in patients who are actively hemolysing. It can therefore only be done several weeks after a hemolytic episode.
| |
| ====Heinz bodies: Early diagnosis====
| |
| 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 [[RBC]]s 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.
| |
|
| |
|
| ==Treatment== | | ==Treatment== |
| * In the acute phase of hemolysis, [[blood transfusion]]s might be necessary. Blood transfusion is an important symptomatic measure, as the transfused red cells are generally not G6PD deficient.
| | [[Glucose-6-phosphate dehydrogenase deficiency medical therapy|Medical Therapy]] | [[Glucose-6-phosphate dehydrogenase deficiency surgery|Surgery]] | [[Glucose-6-phosphate dehydrogenase deficiency primary prevention|Primary Prevention]] | [[Glucose-6-phosphate dehydrogenase deficiency secondary prevention|Secondary Prevention]] | [[Glucose-6-phosphate dehydrogenase deficiency cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Glucose-6-phosphate dehydrogenase deficiency future or investigational therapies|Future or Investigational Therapies]] |
| * [[Dialysis]] in [[acute renal failure]]
| | ==Case Studies== |
| * Some patients benefit from removal of the [[spleen]] ([[splenectomy]]), as this is an important site of [[red blood cell]] destruction. * [[Folic acid]] should be used in any disorder featuring a high [[red blood cell]] turnover.
| | [[Glucose-6-phosphate dehydrogenase deficiency case study one|Case #1]] |
| * Although [[vitamin E]] and [[selenium]] have antioxidant properties, their use does not decrease the severity of [[G6PD deficiency]].
| |
| ==Primary Prevention== | |
| * 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.
| |
|
| |
|
| ==References== | | ==References== |
| {{reflist|2}} | | {{reflist|2}} |
|
| |
| {{Hematology}}
| |
|
| |
|
| [[bn:গ্লুকোজ-৬-ফসফেট ডিহাইড্রোজেনেজ স্বল্পতা]] | | [[bn:গ্লুকোজ-৬-ফসফেট ডিহাইড্রোজেনেজ স্বল্পতা]] |