G6PD Deficiency Flashcards
A 25-year-old African American man presents to the emergency department with dark-colored urine, yellowing of the eyes, and fatigue for the past 2 days. He recently recovered from a respiratory infection and was prescribed trimethoprim-sulfamethoxazole (TMP-SMX). He has no significant past medical history and does not take any chronic medications. On examination, his conjunctivae are icteric, and he has mild pallor. Vital signs are normal. Laboratory studies reveal the following:
Hemoglobin: 9.2 g/dL (normal: 13.5-17.5 g/dL) Hematocrit: 28% (normal: 41-53%) Reticulocyte count: 6% (elevated) Total bilirubin: 5.2 mg/dL (normal: 0.1-1.2 mg/dL) Direct (conjugated) bilirubin: 0.4 mg/dL Lactate dehydrogenase (LDH): elevated Haptoglobin: decreased
A peripheral blood smear reveals bite cells and Heinz bodies.
Which of the following is the most likely cause of this patient’s condition?
a. Decreased erythropoietin production
b. Autoimmune hemolysis
c. Impaired erythrocyte cytoskeletal proteins
d. Glutathione depletion due to enzyme deficiency
e. Hemoglobin polymerization under hypoxic conditions
Correct Answer:
d. Glutathione depletion due to enzyme deficiency
Explanation:
This patient has classic signs and symptoms of acute hemolysis (jaundice, anemia, dark-colored urine) triggered by exposure to an oxidative stressor (use of trimethoprim-sulfamethoxazole, a known oxidizing agent). The key peripheral smear findings of bite cells and Heinz bodies strongly support a diagnosis of Glucose-6-phosphate dehydrogenase (G6PD) deficiency. G6PD is required to produce NADPH, which maintains the supply of reduced glutathione in RBCs. Glutathione neutralizes oxidative stress inside RBCs, and in G6PD deficiency, this protection is lost. Without reduced glutathione, reactive oxygen species (ROS) cause oxidation of hemoglobin, leading to the formation of Heinz bodies (clumps of denatured hemoglobin), which are “bitten out” by splenic macrophages, creating bite cells.
Why does G6PD deficiency have an evolutionary advantage?
G6PD deficiency is more prevalent in regions with malaria because Plasmodium falciparum is less able to infect G6PD-deficient RBCs.
It provides protective benefits against malaria infection.
What are the key differences between G6PD deficiency and hereditary spherocytosis (HS)?
G6PD Deficiency:
Enzyme deficiency (G6PD), Episodic (Oxidative stress), Bite cells, Heinz bodies, Coombs Test Negative, X-linked Recessive Inheritance, Triggered by Infections, Drugs, Fava beans.
Hereditary Spherocytosis:
Cytoskeletal defect (Ankyrin, Spectrin), Chronic hemolysis, Spherocytes (small, round RBCs), Coombs Test Negative, Autosomal Dominant Inheritance, No trigger instead continuous hemolysis
What are the key triggers for G6PD deficiency-related hemolysis?
Infections (increased oxidative stress).
Drugs (primaquine, dapsone, sulfa drugs, nitrofurantoin, isoniazid).
Fava beans (Favism).
What drugs should be avoided in patients with G6PD deficiency?
Antimalarials: Primaquine, chloroquine.
Sulfonamides: Sulfa drugs, TMP-SMX (trimethoprim-sulfamethoxazole).
Nitrofurantoin (for UTI).
Aspirin (high doses).
Dapsone (for leprosy or PCP prophylaxis).
What findings are seen on a peripheral smear in G6PD deficiency?
Heinz bodies (denatured hemoglobin).
Bite cells (due to removal of Heinz bodies by splenic macrophages).
What are Heinz bodies, and how are they visualized?
Heinz bodies are clumps of denatured hemoglobin found inside RBCs.
They are seen on supravital staining (e.g., crystal violet or methylene blue), but not on Wright-Giemsa stain.
What is the enzyme deficiency in G6PD deficiency, and what does it affect?
Deficiency of Glucose-6-phosphate dehydrogenase (G6PD).
Leads to reduced production of NADPH, impairing the reduction of glutathione and making RBCs vulnerable to oxidative stress.
What type of hyperbilirubinemia is seen in G6PD deficiency?
Unconjugated hyperbilirubinemia (due to hemolysis).
Why is hemolysis in G6PD deficiency episodic rather than chronic?
G6PD deficiency only leads to hemolysis in the presence of oxidative stress (e.g., infections, drugs, fava beans).
Between episodes, patients are typically asymptomatic.
How is G6PD deficiency diagnosed?
Peripheral smear: Heinz bodies, bite cells.
G6PD enzyme assay.
When should the G6PD enzyme assay be performed to evaluate for G6PD deficiency?
Performed after resolution of hemolytic episode to avoid false negatives. During active hemolysis, most of the deficient RBCs are destroyed, and only young, healthy RBCs remain, leading to a false-negative G6PD enzyme assay.
How do you differentiate G6PD deficiency from autoimmune hemolytic anemia (AIHA) on peripheral smear?
G6PD deficiency: Bite cells and Heinz bodies.
AIHA: Spherocytes (round, dense RBCs) due to RBC membrane loss from macrophages.
AIHA also has a positive Coombs test, while G6PD does not.
What are the complications of G6PD deficiency if left untreated?
Severe hemolysis requiring transfusion.
Hyperbilirubinemia leading to kernicterus in neonates.
How does G6PD deficiency present in neonates?
Neonatal jaundice within 2-3 days of birth due to hemolysis.
Risk of kernicterus (bilirubin-induced brain dysfunction).
