Glucose-6-phosphate dehydrogenase deficiency pathophysiology

Glucose-6-phosphate dehydrogenase deficiency Microchapters
Home
Patient Information
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating Glucose-6-phosphate dehydrogenase deficiency from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
Diagnostic Study of Choice
History and Symptoms
Physical Examination
Laboratory Findings
Electrocardiogram
Chest X Ray
CT
MRI
Echocardiography or Ultrasound
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Surgery
Primary Prevention
Secondary Prevention
Cost-Effectiveness of Therapy
Future or Investigational Therapies
Case Studies
Case #1
Glucose-6-phosphate dehydrogenase deficiency pathophysiology On the Web
Most recent articles
Most cited articles
Review articles
CME Programs
Powerpoint slides
Images
American Roentgen Ray Society Images of Glucose-6-phosphate dehydrogenase deficiency pathophysiology All Images X-rays Echo & Ultrasound CT Images MRI
Ongoing Trials at Clinical Trials.gov
US National Guidelines Clearinghouse
NICE Guidance
FDA on Glucose-6-phosphate dehydrogenase deficiency pathophysiology
CDC on Glucose-6-phosphate dehydrogenase deficiency pathophysiology
Glucose-6-phosphate dehydrogenase deficiency pathophysiology in the news
Blogs on Glucose-6-phosphate dehydrogenase deficiency pathophysiology
Directions to Hospitals Treating Glucose-6-phosphate dehydrogenase deficiency
Risk calculators and risk factors for Glucose-6-phosphate dehydrogenase deficiency pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Priyamvada Singh, M.D. [2]

Please help WikiDoc by adding content here. It's easy! Click here to learn about editing.

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.
• 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).

Mechanism of G6PD

References

Template:WikiDoc Sources Need content