Lecture: G6PD Deficiency

Introduction

• Discussing G6PD deficiency
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Normocytic Anemias

Classification

• Defined by an MCV that is normal (80-100)
• Subdivided into:
  • Non-hemolytic anemias
  • Hemolytic anemias
    • Intrinsic causes
    • Extrinsic causes

Intrinsic Hemolytic Anemia Causes

• Issues within the red blood cell:
  • Membrane defects
  • Enzyme deficiencies
  • Hemoglobinopathies

Extrinsic Hemolytic Anemia Causes

• Issues outside the red blood cell
  • Autoimmune issues
  • Microangiopathic and macroangiopathic disorders
  • Infections

Reticulocyte Count

• Bone marrow response to hemolysis: increased production of red blood cells
• Increased reticulocyte count (>2%) in hemolytic anemia
• Normal reticulocyte count (1-2%) in non-hemolytic anemia

G6PD Deficiency

Overview

• X-linked recessive disorder
• Leads to intravascular and extravascular hemolysis
• Renders red blood cells more susceptible to oxidative stress

Pathogenesis

• High-stress environment in red blood cells
  • Presence of substances like oxygen, carbon monoxide, and hydrogen peroxide (H2O2)
• NADPH and glutathione pathway:
  • NADPH produced by the HMP shunt, dependent on G6PD
  • NADPH reduces glutathione into its active form
  • Reduced glutathione neutralizes H2O2
• Deficiency in G6PD:
  • Impaired NADPH production
  • Decreased reduced glutathione
  • Increased oxidative stress and red blood cell damage

Causes of Oxidative Stress

• Infections
• Drugs: primaquine, dapsone, sulfa drugs
• Fava beans

Clinical Presentation

• Symptoms triggered by oxidative stress
• Hemoglobinuria
• Back pain (due to nephrotoxic effects of hemoglobin)
• Jaundice, dark urine, anemia

Variants

• African variant: Mildly reduced G6PD half-life, mild intravascular hemolysis
• Mediterranean variant: Significantly reduced G6PD half-life, severe intravascular hemolysis

Protection against Malaria

• Role in protection against Plasmodium falciparum (malaria)
• Infection with malaria increases oxidative stress, leading to destruction of red blood cells

Diagnosis and Treatment

• Diagnosis:
  • Heinz preparation to detect precipitated hemoglobin (Heinz bodies)
  • Blood smear to see bite cells (degmacytes)
  • Enzyme studies post-hemolytic episode
• Treatment:
  • Avoid oxidative stress triggers (fava beans, certain drugs, infections)

Summary

• G6PD Deficiency: Impaired ability to handle oxidative stress due to NADPH pathway disruption
• Key triggers: Infections, certain drugs, fava beans
• Diagnostic features: Heinz bodies, degmacytes
• Treatment: Avoid triggers to prevent oxidative stress

Conclusion

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