G6PD Deficiency

Glucose-6-phosphatase dehydrogenase (G6PD) deficiency is the most common disease-

producing enzymopathy in humans. Inherited as an X-linked disorder, glucose-6-phosphatase
dehydrogenase (G6PD) deficiency affects 400 million people worldwide. The disease is
highly polymorphic, with more than 300 reported variants. It confers protection against
malaria, which probably accounts for its high gene frequency.
[1, 2]
See image below.
Heinz bodies. Acute hemolysis from glucose-6-phosphatase dehydrogenase deficiency
is linked to the development of Heinz bodies, which are composed of denatured hemoglobin.
For excellent patient education resources, visit eMedicineHealth's Children's Health Center.
Also, see eMedicineHealth's patient education article Newborn Jaundice.
Pathophysiology
The G6PD enzyme catalyzes the oxidation of glucose-6-phosphate to 6-phosphogluconate
while concomitantly reducing the oxidized form of nicotinamide adenine dinucleotide
phosphate (NADP
+
) to nicotinamide adenine dinucleotide phosphate (NADPH). NADPH, a
required cofactor in many biosynthetic reactions, maintains glutathione in its reduced form.
Reduced glutathione acts as a scavenger for dangerous oxidative metabolites in the cell. With
the help of the enzyme glutathione peroxidase, reduced glutathione also converts harmful
hydrogen peroxide to water. Red blood cells rely heavily upon glucose-6-phosphatase
dehydrogenase (G6PD) activity because it is the only source of NADPH that protects the
cells against oxidative stresses; therefore, people deficient in glucose-6-phosphatase
dehydrogenase (G6PD) are not prescribed oxidative drugs, because their red blood cells
undergo rapid hemolysis under this stress.
The 5 classes of glucose-6-phosphatase dehydrogenase (G6PD) deficiency include low,
normal, or increased levels of the enzyme.
Epidemiology
Frequency
International
The highest prevalence rates (with gene frequencies from 5-25%) of glucose-6-phosphatase
dehydrogenase (G6PD) deficiency are found in tropical Africa, the Middle East, tropical and
subtropical Asia, some areas of the Mediterranean, and Papua New Guinea.
[3, 4, 5]

Mortality/Morbidity
The most common clinical feature of glucose-6-phosphatase dehydrogenase (G6PD) deficiency is a
lack of symptoms. Symptomatic patients present withneonatal jaundice and acute hemolytic anemia.
Neonatal jaundice: Jaundice usually appears by age 1-4 days, at the same time as or slightly earlier
than so-called physiologic jaundice and later than in in-blood group alloimmunization.
[6, 7]
Kernicterus
is a rare complication.
[8]

Acute hemolytic anemia: Clinical expression results from stress factors such as oxidative drugs or
chemicals, infection, or ingestion of fava beans.
[3, 4, 9, 10]

Race
Glucose-6-phosphatase dehydrogenase (G6PD) deficiency affects all races. The highest prevalence
is among persons of African, Asian, or Mediterranean descent.
[3, 4]
The severity of glucose-6-
phosphatase dehydrogenase (G6PD) deficiency varies significantly among racial groups because of
different variants of the enzyme. Severe deficiency variants primarily occur in the Mediterranean
population. The enzymatic variants in the African population have more activity and produce a milder
form of the disease.
Sex
Glucose-6-phosphatase dehydrogenase (G6PD) deficiency is an X-linked inherited disease that
primarily affects men.
Homozygous women are found in populations in which the frequency of glucose-6-phosphatase
dehydrogenase (G6PD) deficiency is quite high.
Heterozygous (carrier) women can develop hemolytic attacks.