U01.01.097 Glucose-6-phosphate dehydrogenase deficiency

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked recessive disorder affecting red blood cells (RBCs). It leads to hemolytic anemia due to impaired RBC defense against oxidative stress.

Key Functions of G6PD

NADPH Production: G6PD is a crucial enzyme in the pentose phosphate pathway, responsible for generating nicotinamide adenine dinucleotide phosphate (NADPH).
Role of NADPH:
- Maintains reduced glutathione (GSH), which detoxifies free radicals and peroxides.
- Protects RBCs from oxidative damage.

Pathophysiology

Mechanism	Impact
NADPH Deficiency	Reduced levels of GSH, leading to increased vulnerability to oxidative stress.
Hemolysis	Poor RBC defense against oxidizing agents results in hemolytic anemia.
Common Triggers	– Oxidative drugs (e.g., sulfonamides, nitrofurantoin, primaquine)

markdownCopy code                                  - Infections (most common cause, producing free radicals).  
                                  - Fava beans (oxidizing agents).   |

Clinical Features

Feature	Description
Hemolytic Anemia	Occurs due to oxidative damage to RBCs.
Heinz Bodies	Denatured hemoglobin precipitates in RBCs during oxidative stress.
Bite Cells	RBCs with “bites” removed by splenic macrophages after phagocytosis of Heinz bodies.

Mnemonic: “Bite into some Heinz ketchup” to remember bite cells and Heinz bodies.

Epidemiology

Most common enzyme deficiency worldwide.
Prevalence: Higher among African Americans and individuals from malaria-endemic regions (confers malarial resistance).

Biochemical Pathway

The biochemical pathway involving G6PD deficiency:

Enzyme	Substrate/Product	Function
Glucose-6-Phosphate Dehydrogenase	Glucose-6-Phosphate → 6-Phosphogluconolactone	Produces NADPH.
Glutathione Reductase	NADP⁺ + 2 GSH → GSSG + NADPH	Regenerates reduced glutathione.
Glutathione Peroxidase	H₂O₂ + 2 GSH → 2 H₂O + GSSG	Neutralizes hydrogen peroxide.

Points to Remember

NADPH is critical for maintaining reduced glutathione, detoxifying free radicals.
Hemolytic anemia arises due to oxidative stress from drugs, infections, or dietary triggers.
Heinz bodies and bite cells are characteristic findings on peripheral blood smear.
G6PD deficiency is X-linked recessive and provides partial protection against malaria.

Bibliography

Kaplan Medical USMLE Step 1 Review Books
First Aid for the USMLE Step 1
Harrison’s Principles of Internal Medicine

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