G6pd deficiency means?
G6PD deficiency is a genetic disorder where the enzyme glucose-6-phosphate dehydrogenase is absent or reduced. This enzyme protects red blood cells from oxidative damage. Without it, red blood cells break down prematurely (hemolysis) when exposed to triggers like certain drugs, infections, or foods (notably fava beans). It is X-linked recessive, so it mostly affects males.
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G6PD deficiency mechanism clinical features treatment 2024
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Here is a thorough explanation of G6PD deficiency sourced from Harrison's and Lippincott Illustrated Biochemistry:
G6PD Deficiency (Glucose-6-Phosphate Dehydrogenase Deficiency)
What Is It?
G6PD deficiency is the most common disease-producing enzyme abnormality in humans, affecting over 400-500 million people worldwide. It is a hereditary condition caused by mutations in the G6PD gene on the X chromosome, resulting in reduced or absent activity of the G6PD enzyme in red blood cells.
- Inheritance: X-linked recessive - affects mostly males (hemizygous)
- Epidemiology: Highest prevalence in persons from tropical Africa, the Middle East, Asia, and the Mediterranean region
- Evolutionary advantage: G6PD deficiency confers partial protection against Plasmodium falciparum malaria, which explains its geographic distribution
The Biochemical Mechanism
The diagram below (from Lippincott Biochemistry) explains it visually:
- G6PD is the first enzyme of the pentose phosphate pathway (PPP)
- It converts glucose-6-phosphate to 6-phosphogluconolactone, producing NADPH
- NADPH is needed by glutathione reductase to keep glutathione in its reduced (active) form (G-SH)
- Reduced glutathione (G-SH) neutralizes H2O2 and other free radicals via glutathione peroxidase
- Without G6PD: no NADPH → no reduced glutathione → oxidative damage accumulates → hemolysis
Red blood cells are uniquely vulnerable because:
- The PPP is their only source of NADPH
- They have no nucleus or ribosomes and cannot renew enzyme supply
- Lippincott Biochemistry, 8th ed., p. 445-449
Triggers (Precipitating Factors)
Most people are asymptomatic until exposed to an oxidant stress:
| Trigger | Examples |
|---|---|
| Oxidant drugs | Sulfa antibiotics, primaquine, dapsone, nitrofurantoin, some analgesics/antipyretics |
| Fava beans (Favism) | Especially the Mediterranean variant |
| Infection | Inflammatory response generates free radicals in macrophages that diffuse into RBCs |
Classification by Severity
| Class | Symptoms | Residual Enzyme Activity |
|---|---|---|
| I | Very severe - chronic non-spherocytic hemolytic anemia (CNSHA) | <10% |
| II | Severe - acute hemolytic anemia (e.g., G6PD Mediterranean) | <10% |
| III | Moderate (e.g., G6PD A-, most common in Africans) | 10-60% |
| IV | No symptoms | >60% |
Classes II and III are the most common forms.
Clinical Features
- Acute hemolytic anemia (AHA) - triggered by above factors, usually self-limiting in 8-14 days (because younger red cells have more G6PD activity and are spared)
- Neonatal jaundice (NNJ) - appears 1-4 days after birth, due to elevated unconjugated bilirubin; may be severe
- Heinz bodies - denatured hemoglobin forms insoluble masses (visible on special staining), leading to rigid, less deformable RBCs that are removed by the spleen and liver
- Chronic non-spherocytic hemolytic anemia (CNSHA) - only in Class I (rare)
- "Bite cells" - RBCs with a chunk removed by the spleen (seen on peripheral smear)
Diagnosis
- G6PD enzyme assay (quantitative) - gold standard
- Peripheral blood smear showing Heinz bodies and bite cells
- Note: Do NOT test during an acute hemolytic episode - the oldest (most deficient) cells are destroyed first, leaving younger cells with normal G6PD levels, giving a false-normal result
Management
- Acute episodes: Mostly supportive; remove the offending trigger. Blood transfusion if anemia is severe. Hemodialysis if acute renal failure develops
- Favism: Completely preventable by avoiding fava beans
- Drug-induced: Screen before prescribing known oxidant drugs; use alternative drugs
- Neonatal jaundice: Phototherapy or exchange transfusion (same management as NNJ from other causes)
- CNSHA (Class I): Folic acid supplements, hematologic surveillance; splenectomy has been beneficial in severe cases
- Harrison's Principles of Internal Medicine, 22E (2025), p. treatment section
Key Point Summary
G6PD deficiency = no NADPH → no reduced glutathione → RBCs cannot fight oxidative stress → hemolysis when triggered. Most people are fine until exposed to drugs, infections, or fava beans.
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