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Glucose 6 phosphate dehydrogenase is an enzyme in the Hexose Monophosphate shunt.
This shunt generates reduced glutathione that protects sulfhydryl groups of hemoglobin and
the red cell membrane from oxidation by the oxygen radicals. Defects in the shunt leads to
inadequate protection against oxidation, resulting in oxidation of sulfhydryl groups and
precipitation of hemoglobin as Heinz bodies and in lysis of the red cell membrane.
The Hexose
Monophosphate Shunt
Deficiency of Glucose 6
phosphate dehydrogenase is the most common among the congenital shunt defects, affecting
more than 200 million people in the world. There is considerable genetic heterogeneity
among affected individuals with over 400 variants of the enzyme identified. Therefore the
severity of the problem can vary from hemolysis even in the absence of oxidative stress to
hemolysis only on exposure to mild to marked oxidant stress.
The normal G6PD is called as
Type B. Type A- has two base substitutions and is seen in people from central Africa. A
second variant is seen among the people of the Mediterranian and is more severe than Type
A-. The third variant that is relatively more common but less severe is seen in southern
China.
The defect is known to
provide partial protection against malaria, by providing defective environment in the
affected red cells.
The G6PD gene is located on
the X chromosome. Thus the deficiency state is an sex-linked trait seen only in hemizygote
males. Most female carriers are asymptomatic.
Hemolytic episodes may be
triggered by viral or bacterial infections and by drugs or toxins that have an oxidating
potential. Antimalarials like primaquine, pamaquine, dapsone, sulfonamides like
sulfamethoxazole, nitrofurantoin, vitamin K, doxorubicin, methylene blue, nalidixic acid,
furazolidone etc. and naphthalene balls can cause hemolysis in defective
individuals.
The hemolytic crisis may
manifest within hours of exposure to oxidant stress. In severe cases, hemoglobinuria and
peripheral circulatory collapse can occur. Since only older red cells are affected most,
the problem is usually self-limiting. There will be a rapid drop in hematocrit, rise in
plasma hemoglobin and unconjugated bilirubin. Heinz bodies can be seen on crystal violet
staining. These are removed in the spleen in a day or two and 'bite cells', with loss of a
portion of the periphery of the red cell, may be seen.
The diagnosis can be
confirmed by G6PD assay. The test may be negative during a hemolytic crisis when the older
and defective RBCs are replaced by younger cells. In such cases, the test has to be
repeated.
No specific treatment is
needed since the condition is usually self limiting. Rarely blood transfusions are
indicated. Adequate urine output should be ensured.
In patients with mild
deficiency of G6PD, primaquine can be given at a dose of 0.6 mg/kg once weekly for 8
weeks. Primaquine and Pyrimethamine+sulfadoxine should not be administered on the same day
to avoid a possible hemolysis.
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