Transcript HEREDITARY ANEMIAS

Enzymopathies = ENZYME DEFECTS
G6PD Deficiency
(Glucose 6 phosphate dehydrogenase Deficiency)
Objectives
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To review the role of G6PD enzyme, and the red
cell metabolism.
To define G6PD deficiency as a hemolytic anemia.
List the lab. Findings in G6PD deficiency.
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G6PD deficiency is an inherited condition.
Which cause a non immune hemolytic anemia.
Commonest red cell enzymopathy affecting over
400 million people world wide.
The G6PD enzyme catalyzes an
oxidation/reduction reaction.
G6PD in red cell essential for preventing
Oxidative damage to red cells
So cell lacking the enzyme are susceptible to
oxidant induced hemolysis.
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G6PD functions in catalyzing the oxidation of G6P to
6-phosphogluconate, while reducing NADP to
NADPH; this is the first step in the pentose phosphate
pathway.
So G6PD is responsible for maintaining adequate levels
of NADPH inside the cell.
NADPH is used to keep glutathione, in its reduced
form . Reduced glutathione acts as a scavenger ‫ ك ّناس‬for
dangerous oxidative metabolites in the cell; it converts
harmful hydrogen peroxide to water .
There are other metabolic pathways that can generate
NADPH in all cells, except in red blood cells where
other NADPH-producing enzymes are lacking.
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G6PD deficiency is also sometimes referred to
as favism since some G6PD deficient individuals
are also allergic to fava beans.
All patients with favism are
G6PD deficient, but many
G6PD-deficient individuals can
regularly eat fava beans
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Sex-linked inheritance. Affect males. Females
are carriers.(they have ½ of RBCs with normal
enzyme activity).
G6PD activity is  mostly in old cells.
CLINICALLY
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Usually a symptomatic.
Acute hemolysis due to oxidant stress. E.g. :
Drugs, Infection, fava beans.
Hemolysis is Intravascular. (Hemoglobinuria).
The anemia may be self-limiting because new
red cells (with normal enzyme activity) are
produced.
Neonatal jaundice.
Lab. Diagnosis
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Between crisis, blood count is normal.
During crisis, features of intravascular
hemolysis.
Blood film show : contracted & fragmented cells.
Bite/Blister cells : loss of cytoplasm with
separation of remaining Hb from cell membrane.
Subravital stain : Heinz bodies
oxidized
denatured Hb.
Reticulocytosis during hemolysis.
Bite cells/Blister cells
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Bite ‫ عضة أو قضمة‬cells are formed when Heinz
bodies (the product of oxidant stress on the
haemoglobin molecule) together with some red
cell content, are removed from red cells as they
pass through the spleen.
When the red cell membrane around the bite
repairs, a blister-like structure forms, hence the
term blister cell. Blister = ‫بثرة أو قرحة‬
arrow indicates a “bite” cell, or keratocyte
arrows indicate “blister cells,” and arrowheads
irregularly contracted cells
Heinz bodies are red cells’ inclusions composed of oxidized
denatured hemoglobin. Heinz bodies appear as small round
inclusions within the red cell, though when stained with
Romanowsky stains they may appear as projections from the
cell. They appear more clearly when supravitally stained
6. Screening Tests for G6PD Deficiency
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Flurescent Screening test. (G6PD will produce NADPH from
NADP+.These NADPHs will fluoresces under UV light. In G6PD deficiency,less fluoresces
occur due to less NADPH production)
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Methaemoglobin Reduction test .
During and immediately after a hemolytic
episode, tests may yield false-negative results
because of destruction of the older, more
deficient RBCs and the presence of reticulocytes
rich in G6PD.
7. Enzyme assay
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Spectrophotometric enzyme assays.
The activity of the enzyme is assayed by following the
rate of production of NADPH, which, unlike
NADP, has a peak of UV light absorption at 340
nm.