Glucose-6-Phosphate Dehydrogenase Deficiency (G6PD deficiency)

Epidemiology and Etiology:

• Hexose monophosphate shunt abnormalities
• Glutathione metabolism abnormalities
• Reduction in ability of red cells to protect themselves against oxidative injuries and lead to hemolysis (intravascular and extravascular)
• X-linked recessive (G6PD) most commonly
• Episodes caused by exposures that generate oxidant stress
• Infections (most common)
• Oxygen-derived free radicals are produced by activated leukocytes
• Viral hepatitis
• Pneumonia
• Typhoid fever
• Drugs
• Antimalarials
• Sulfonamides
• Nitrofurantoins
• others
• Foods
• Fava bean (Favism)

Common sites:

Gross features:

Microscopic features:

• Peripheral Blood:
• Heinz bodies (revealed by supravital staining)
• Dark inclusions within red cells stained with crystal violet
• Bite cells
• Spherocytes
• Reticulocytosis (recovery phase)

Immunophenotype:

Marker:

Sensitivity:

Specificity:

Molecular features:

• Glucose-6-phosphate dehydrogenase (G6PD) variants (most common)
• G6PD ^– (10% of American blacks)
• G6PD Mediterranean (prevalent in the Middle East, more severe phenotype)
• Many other harmless variants
• Note these two variants also result in protective effect against Plasmodium falciparum malaria
• Result in misfolding of the protein making it more susceptible to proteolytic degradation

Other features:

• Episodic hemolysis
• Acute intravascular hemolysis 2-3 days after exposure to oxidants
• Anemia
• Hemoglobinemia
• Hemoglobinuria
• ABSENT - Features of chronic hemolysis (splenomegaly, cholelithiasis)

References:

• Kumar V, Abbas AK, Fausto N, Aster JC, eds. Robbins and Cotran Pathologic Basis of Disease, 8^th ed. (2010)