Glucose-6-phosphate dehydrogenase deficiency pathophysiology
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Glucose-6-phosphate dehydrogenase deficiency Microchapters |
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Differentiating Glucose-6-phosphate dehydrogenase deficiency from other Diseases |
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Diagnosis |
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Treatment |
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Case Studies |
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Glucose-6-phosphate dehydrogenase deficiency pathophysiology On the Web |
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American Roentgen Ray Society Images of Glucose-6-phosphate dehydrogenase deficiency pathophysiology |
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FDA on Glucose-6-phosphate dehydrogenase deficiency pathophysiology |
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CDC on Glucose-6-phosphate dehydrogenase deficiency pathophysiology |
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Glucose-6-phosphate dehydrogenase deficiency pathophysiology in the news |
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Directions to Hospitals Treating Glucose-6-phosphate dehydrogenase deficiency |
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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: Mahda Alihashemi M.D. [2]
Overview
The exact pathogenesis of [disease name] is not fully understood.
OR
It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
OR
[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
OR
Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
OR
[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
OR
The progression to [disease name] usually involves the [molecular pathway].
OR
The pathophysiology of [disease/malignancy] depends on the histological subtype.
Pathophysiology
Physiology
The normal physiology of [name of process] can be understood as follows:
Pathogenesis
- The exact pathogenesis of [disease name] is not completely understood.
OR
- It is understood that G6PD deficiency is the result of reduced Glucose-6-phosphate dehydrogenase enzyme levels. G6PD deficiency is an X-linked disorder. It is the most common enzymatic disorder of red blood cells. Glucose-6-phosphate dehydrogenase enzyme oxidize glucose-6-phosphate to 6-phosphogluconolactone in pentose phosphate pathway ( HMP shunt). Glucose-6-phosphate dehydrogenase enzyme also reduces nicotinamide adenine dinucleotide phosphate (NADP) to NADPH. NADPH is an important cofactor in glutathione metabolism against oxidative injury in RBC.Reduced glutathione (GSH) convert to oxidized glutathione (GSSG) by glutathione peroxidase enzyme that prevent oxidant accumulation. Glutathione reductase catalyzes the reduction of GSSG to GSH by NADPH. In G6PD deficiency, oxidative stresses can denature hemoglobin and intravascular hemolysis in RBC can happen. Infection, some meication and foods with high level of convicine, vicine, divicine and isouramil such as fava beans can cause oxidative stress. Spleen is the organ for sequesteration damaged RBC. The hemoglobin is metabolized to bilirubin and cause jaundice.
- [Pathogen name] is usually transmitted via the [transmission route] route to the human host.
- Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
- [Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
- The progression to [disease name] usually involves the [molecular pathway].
- The pathophysiology of [disease/malignancy] depends on the histological subtype.
Genetics
G6PD deficiency is transmitted in x-linked disorder pattern.
The gene for G6PD is located on the X chromosome (band X q28) [8] and has been cloned and sequenced [9-11]. Even though females have two X chromosomes per cell, males and females have the same enzyme activity in their red cells because one of the X chromosomes in each cell of the female embryo is inactivated and remains inactive throughout subsequent cell divisions (Lyon hypothesis) [12].
G6PD deficiency is expressed in males carrying a variant gene, while heterozygous females are usually clinically normal. However, the mean red blood cell enzyme activity in heterozygous females may be normal, moderately reduced, or grossly deficient depending upon the degree of lyonization and the degree to which the abnormal G6PD variant is expressed [13]. A heterozygous female with 50 percent normal G6PD activity has 50 percent normal red cells and 50 percent G6PD-deficient red cells. The deficient cells are as vulnerable to hemolysis as the enzyme-deficient red blood cells in males.
It is of interest that the incidence of G6PD deficiency in Chinese females ≥80 years of age was several-fold greater than what was expected from population screening at birth [14]. It is thought that this is due to the skewed X-inactivation that occurs with aging.
G6PD and its variants — The monomeric form of G6PD contains 515 amino acids, but the active form of G6PD is a dimer that contains tightly bound NADP [15,16]. Amino acid 205 is the binding site for glucose-6-phosphate, while amino acids 386 and 387 may be involved in binding to NADP [15,17].
The normal or wild-type enzyme is called G6PD B, although over 400 variant enzymes have been identified [15,16,18,19]. By international agreement, standardized methods have been used to characterize these enzyme variants, which differ on the basis of their biochemical properties, such as kinetic activity and the Michaelis constant for its substrate glucose-6-phosphate and cofactor NADP [20,21]. However, differences between some variants are subtle and may not represent true enzyme differences.
The variants are almost all missense point mutations, although a few deletions have been described [15,18]. Large deletions or frame shift mutations have not been identified, suggesting that complete absence of G6PD may be lethal [15]. Most class I variants that are associated with chronic hemolytic anemia have abnormalities in the glucose-6-phosphate binding or NADP binding site of the enzyme (figure 2) [15].
OR
Genes involved in the pathogenesis of G6PD deficency include:
- [Gene1]
- [Gene2]
- [Gene3]
OR
The development of [disease name] is the result of multiple genetic mutations such as:
- [Mutation 1]
- [Mutation 2]
- [Mutation 3]
Associated Conditions
Gross Pathology
On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
Microscopic Pathology
On microscopic histopathological analysis, , Heinz bodies can be visualized as a result of denatured hemoglobin in peripheral blood smears with supravital staining. processed with supravital staining (Heinz body prep).
References
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Glucose-6-phosphate dehydrogenase deficiency Microchapters |
|
Differentiating Glucose-6-phosphate dehydrogenase deficiency from other Diseases |
|---|
|
Diagnosis |
|
Treatment |
|
Case Studies |
|
Glucose-6-phosphate dehydrogenase deficiency pathophysiology On the Web |
|
American Roentgen Ray Society Images of Glucose-6-phosphate dehydrogenase deficiency pathophysiology |
|
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. [3]; Associate Editor(s)-In-Chief: Priyamvada Singh, M.D. [4]
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Overview
Pathophysiology
