Glucose-6-phosphate dehydrogenase (G6PD) deficiency

What fundamental process is impaired in Glucose-6-phosphate dehydrogenase (G6PD) deficiency?

The regeneration of reduced glutathione, an important antioxidant. Summary 1

What is the main consequence of impaired glutathione regeneration in G6PD deficiency for red blood cells (RBCs)?

RBCs become more susceptible to oxidative stress, potentially resulting in episodic hemolytic anemia. Summary / Patho 2

How is Glucose-6-phosphate dehydrogenase (G6PD) deficiency inherited?

In an X-linked recessive pattern. Summary / Patho 3

What is the global prevalence status of Glucose-6-phosphate dehydrogenase (G6PD) deficiency?

It is the most common human enzyme deficiency worldwide. Summary / Epi 4

Which populations are primarily affected by Glucose-6-phosphate dehydrogenase (G6PD) deficiency?

Primarily males of African, Asian, and Mediterranean descent. Summary / Epi 5

What is the typical clinical state for individuals with G6PD deficiency?

Usually asymptomatic. Summary / Clin 6

What can trigger a hemolytic crisis in individuals with G6PD deficiency?

A sudden surge in oxidative stress (e.g., after infection, consumption of fava beans, or various drugs). Summary / Patho 7

What are key diagnostic findings in G6PD deficiency related to hemolysis and blood smear?

Signs of intravascular hemolysis (normocytic anemia, ↑ LDH, ↓ haptoglobin), Heinz bodies, and bite cells on blood smear. Summary / Dx 8

What is the cornerstone of managing Glucose-6-phosphate dehydrogenase (G6PD) deficiency?

Prevention of hemolysis by avoiding triggers. Summary / Tx 9

Approximately how many people worldwide have Glucose-6-phosphate dehydrogenase (G6PD) deficiency?

Approximately 400 million people worldwide. Epidemiology 10

What is the role of G6PD enzyme in cellular metabolism?

It is the rate-limiting enzyme of the pentose phosphate pathway (hexose monophosphate shunt). Pathophysiology 11

What crucial molecule is produced by the pentose phosphate pathway, facilitated by G6PD?

NADPH (Nicotinamide adenine dinucleotide phosphate). Pathophysiology 12

Why is NADPH essential for red blood cell protection?

It is required to convert oxidized glutathione back to its reduced form. Pathophysiology 13

What is the protective function of reduced glutathione in red blood cells?

It neutralizes reactive oxygen species (ROS) and free radicals, protecting RBCs from oxidative damage. Pathophysiology 14

In G6PD deficiency, what makes RBCs susceptible to damage leading to hemolysis?

The absence (or deficiency) of reduced glutathione makes RBCs susceptible to oxidative stress, damaging erythrocyte membranes and causing hemolysis. Pathophysiology 15

What type of hemolysis occurs in G6PD deficiency?

Both intravascular and extravascular hemolysis can occur due to RBC damage from oxidative stress. Pathophysiology 16

Name a specific food item known to trigger hemolytic crises in G6PD deficiency.

Fava beans. Pathophysiology 17

List categories or specific examples of drugs that can trigger hemolysis in G6PD deficiency.

Antimalarials (chloroquine, primaquine), sulfa drugs (TMP-SMX), nitrofurantoin, isoniazid, dapsone, NSAIDs, ciprofloxacin, chloramphenicol. Pathophysiology 18

What is the most common trigger for hemolytic crises in individuals with G6PD deficiency?

Bacterial and viral infections. Pathophysiology 19

How can inflammation trigger hemolysis in G6PD deficiency?

Free radicals produced during inflammation can diffuse into RBCs, causing oxidative stress. Pathophysiology 20

How can severe G6PD deficiency affect phagocytic immune cells?

Reduced NADPH production can inhibit respiratory burst activity in phagocytes. Pathophysiology 21

When do symptoms of a hemolytic crisis typically arise after exposure to a trigger in G6PD deficiency?

Within 2-3 days after increased oxidative stress. Clinical Features 22

What are the acute symptoms experienced during a hemolytic crisis in G6PD deficiency?

Sudden onset of back or abdominal pain, jaundice, and dark urine. Clinical Features 23

What physical finding related to the spleen might occur during a hemolytic crisis in G6PD deficiency?

Transient splenomegaly. Clinical Features 24

What other clinical manifestation (besides hemolysis) can occur in G6PD deficiency, mimicking another disorder?

Recurrent severe infections, causing symptoms similar to chronic granulomatous disease (due to impaired respiratory burst). Clinical Features 25

What specific inclusions are seen on a blood smear in G6PD deficiency due to hemoglobin precipitation?

Heinz bodies (formed from precipitated, denatured hemoglobin due to oxidative stress). Diagnosis 26

What characteristic red blood cell morphology results from macrophage removal of Heinz bodies in G6PD deficiency?

Bite cells. Diagnosis 27

What are the typical laboratory findings indicating intravascular hemolysis in G6PD deficiency?

Normocytic anemia, increased reticulocyte count, increased unconjugated bilirubin, increased LDH, decreased haptoglobin, and potentially hemoglobinuria. Diagnosis 28

What screening test is used for G6PD deficiency, and what does it measure?

The fluorescent spot test; it measures the production of fluorescent NADPH from NADP when G6PD is active. Diagnosis 29

What result on the fluorescent spot test indicates G6PD deficiency?

A lack of fluorescence (as NADPH is not adequately produced). Diagnosis 30

What is the confirmatory test for diagnosing G6PD deficiency?

Quantitative G6PD enzyme analysis (assay). Diagnosis 31

When is the ideal time to perform diagnostic tests (screening or confirmatory) for G6PD deficiency?

Ideally during remission (when enzyme levels reflect baseline, not falsely elevated by reticulocytosis during a crisis). Diagnosis 32

What is the primary treatment strategy for G6PD deficiency?

Strict avoidance of known triggers (specific foods like fava beans, certain drugs, prompt treatment of infections). Treatment 33

When are blood transfusions indicated in G6PD deficiency?

Only in rare, severe cases of hemolytic anemia. Treatment 34

What evolutionary advantage might G6PD deficiency confer in certain regions?

It may provide a selective advantage by offering partial protection against malaria, especially from Plasmodium falciparum. Miscellaneous 35