Glucose 6 Phosphatase Dehydrogenase Deficiency
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Transcript of Glucose 6 Phosphatase Dehydrogenase Deficiency
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Glucose-6-phosphate
Dehydrogenase Deficiency
yG6PD Deficiency: an inherited disease
characterized by hemolyticanemiacaused by the inability to detoxify
oxidizing agents.
yMost common disease-producing
enzyme abnormality in humans.
yOver 200 million people.
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yHas the highest prevalence in theMiddle East, tropical Africa and Asia,and parts of the Mediterranean.
yX-linked
yLife span of individuals is shortenedas a result of complications arising
from chronic hemolysis.y Increased resistance to malaria
shown by female carriers.
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Note: red blood cell, while biochemically
complex, is a relatively simple cell (no
nucleus, organelles, and protein-synthesizing machinery).
ySo, defects in any of the remaining
components-enzymes, membrane, andhemoglobin-can lead to hemolysis.
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Pathogenesis ofHemolysis in G6PD
Deficiency
Glutathione: a tripeptide found in
nearly all cells, plays a variety of
roles.
Glutathione (GSH), is its reduced
forms, can chemically detoxify
free radicals.
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Free radicals: compounds with one or
more unpaired electron shell. Take
electrons from other compounds andare thus very destructive to cell
membranes, proteins, and DNA.
Implicated in cancer, inflammatory
disease, and aging.
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If the G6PD is missing, it can no longer
convert NADP+to NADPH.
Since NADPH is essential for the
maintenance of the reduced glutathione
pool, glutathione is now oxidized (GS-SG), not reduced (GSH).
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No protection against free radicals and
peroxides formed within the cell.
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Other tissues have alternative sources
ofNADPH production that can keep
glutathione reduced.
The erythrocyte has no nucleus or
ribosomes and can not renew itssupply of the enzyme.
Result: hemolytic anemia
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Clinical Symptoms
y Patient may complain of dyspneaor fatigue (caused by anemia)
y Dark urine and, occasionally, backpain may be reported by patients(caused by hemolysis).
y Skin appear jaundiced or pale.
y A resting heartbeat with a flowmurmur may be present if theanemia is pronounced.
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There are many variations of G6PD
Deficiency - most individuals never
show any clinical manifestations.
Some patients, however, develop
hemolytic anemia if they are
1) treated with an oxidant drug
2) ingest fava beans
3) contact a severe infection
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1) Oxidant drugs: commonly used drugs
that produce hemolytic anemia in
patients with G6PD deficiency arebest remembered from the mnemonic
AAA:
Antibiotics (e.g. sulfamethoxazole)Antimalarials (e.g. primaquine)
Antipyretics (e.g. acetanilid)
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2) Favism: some forms of G6PDDeficiency are susceptible to the
hemolytic effect of the fava bean,which is a staple in the Mediterraneanregion.
Note: favism is not observed in allindividuals with G6PD Deficiency, butall patients with favism have G6PDDeficiency.
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3) Infection: most common factor of
hemolysis in G6PD deficiency:
Reaction: infection inflammatory
response free radicals diffuse into
RBC oxidative damage.
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TreatmentStop taking AAA drugs
Stop eating fava beans
Treat infection promptly