Biology of Disease

GLUCOSE 6-PHOSPHATE DEHYDROGENASE DEFICIENCY (G6PD)

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Margin Note 13.9 Favism

Broad beans were the only edible

bean known in Europe until new

species were brought from the New

World. However, the philosopher

Pythagoras forbade his followers to

eat broad beans on the grounds that

the beans contained the souls of the

dead.

i

Group Examples

Antimalarials pamaquine, primaquine, pentaquine, atabrine, quinine*

Analgesics aspirin (high dose), phenacetin

Antibacterials chloramphenicol*, nitrofurantoin, furazolidine

Sulfonamides sulfacetamide, sulfanilamide, sulfapyridine

Sulfones dapsone, thiazolesulfone, diphenylsulfone

Arsenicals neoarsphenamine

Chemicals methylene blue, naphthalene, phenylhydrazine, toluidine blue, nitrite, ascorbic

acid (large doses), nalidixic acid

*only in the Mediterranean type.

Table 13.7Examples of drugs and chemicals that can cause acute hemolytic anemia in individuals
with G6PD deficiency

a toxic product of a number of reactions. Hydrogen peroxide can react with
unsaturated fatty acids in the erythrocyte membrane forming hydroperoxides,
damaging the membrane (Chapter 12) and leading to premature cell lysis.
The peroxides are eliminated by the action of glutathione peroxidase, which
requires glutathione as a reducing agent:

Glutathione peroxidase

2GSH + R-O-O-H GSSG + ROH + H 2 O

reduced peroxide oxidized glutathione
glutathione

There is only a limited amount of glutathione in the cell and the reduced
form must be regenerated. This takes place in an NADPH-requiring reaction,
catalyzed by glutathione reductase:

Glutathione reductase

GSSG + NADPH + H+ 2GSH + NADP+

Consequently a steady supply of NADPH is required for erythrocyte integrity.

Glucose 6-phosphate dehydrogenase activity is highest in the immature
erythrocytes or reticulocytes and declines as the mature erythrocytes age. In
a hemolytic crisis, the older erythrocytes are destroyed first, leaving behind
reticulocytes and so giving a higher reticulocyte count. Consequently,
measuring the G6PDH activity in the erythrocytes following a crisis can
lead to spuriously high values. If the patient survives the crisis, with or
without transfusions, recovery will usually occur quite rapidly as the
reticulocyte count increases even if the individual continues to take the
antimalarial, because the reticulocytes can synthesize glucose 6-phosphate
dehydrogenase.

Favism

Favism is a hemolytic crisis brought on by the consumption of fava or broad
beans (Vicia fava) by some, but not all, individuals with G6PD. Infants
are especially susceptible. It is not understood why only some patients are
susceptible but it has been suggested that another mutation must also be
present for favism to be shown. Broad beans contain small quantities of toxic
glycosides, which, like the antimalarials, increase the demand for NADPH.