Glucose 6 Phosphate Dehydrogenase Deficiency
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Introduction
Glucose 6 Phosphate Dehydrogenase (G6PD) deficiency is the most common enzymatic disorder worldwide, affecting more than 200 million individuals. It causes bouts of acute hemolytic anemia following exposure to oxidizing substances, and it is important to have a high index of suspicion in at-risk populations who develop anemia after a possible trigger.
Disease severity is classified by the magnitude of enzyme deficiency and degree of hemolysis.
The Case of...
a simple case introducing clincial presentation and calling for a differential diagnosis. To get students thinking.
Causes and Risk Factors
G6PD is an X-linked disease, with multiple identified mutations. As such, it primarily affects males.
It has the highest prevalence in the Middle East, Africa and Asia, and parts of the Mediterranean. G6PD deficiency is thought to protect against infection by malaria.
Oxidants known to precipitate acute hemolytic anemia include:
- fava beans
- antimalarials such as primiquine
- sulfonamide antibiotics
- dapsone
- aspirin
- phenacetin
- infections
- acidosis
Pathophysiology
G6PD is a critical enzyme in the HMP shunt pathway, and is required to maintain reduced glutathione and protect RBCs from oxidation. Enzyme deficiency therefore leads to RBCs that are unable to protect themselves against oxidative stress. When oxidized, hemoglobin precipitates out of solution and forming Heinz bodies.
Splenic macrophages phagocytose these Heinz bodies to form 'bite cells' or 'cookie cells'. These cells are eventually destroyed, leading to anemia.
Signs and Symptoms
- history
- physical exam
History
Patients present with acute hemolytic anemia after a triggering event.
Anemia causes:
- fatigue
- shortness of breath
- pallor
Hemolysis can lead to:
- dark urine (hemoglobinuria)
- jaundice
A careful inquiry into the potential causes (as above) should be carried out.
Neonatal jaundice can be seen.
Physical Exam
Investigations
- lab investigations
- diagnostic imaging
Lab Investigations
A complete blood count shows anemia that is often normocytic.
A blood smear shows characteristic bite cells and Heinz bodies.
evidence of hemolytic anemia:
- hemoglobinuria
- decreased haptoglobin
- increased LDH
- increased indirect bilirubin
G6PD levels can also be measured.
Diagnostic Imaging
Differential Diagnosis
Other causes of anemia should be considered.
Treatments
Following acute attacks, treatment is supportive, especially through hydration. Transfusions are given as required. Phototherapy can be used to degrade bilirubin.
Prevention, through the avoidance of known precipitants, is extremely important.
Splenectomy may be considered for patients with severe episodes of hemolysis.
Consequences and Course
Chronic anemia is rare.
Resources and References
Topic Development
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