Can Glucose-6-phosphate dehydrogenase (G6PD) deficiency cause elevated Creatine Phosphokinase (CPK) levels?

G6PD Deficiency and Elevated CPK Levels

Yes, G6PD deficiency can cause elevated CPK levels, particularly during hemolytic episodes or when the deficiency affects muscle tissue. While G6PD deficiency is primarily known for causing hemolytic anemia, there is evidence supporting its association with elevated creatine phosphokinase (CPK) levels in certain cases.

Mechanisms of CPK Elevation in G6PD Deficiency

G6PD deficiency can lead to elevated CPK through several mechanisms:

1. Muscle G6PD Deficiency

   • G6PD deficiency can affect muscle tissue, not just red blood cells
   • Research has documented cases of muscle G6PD deficiency with elevated CPK levels 1
   • The Mediterranean variant of G6PD deficiency has been specifically linked to muscle involvement

2. Oxidative Stress Effects

   • G6PD deficiency reduces the ability to mitigate oxidative stress due to lower NADPH levels 2
   • This oxidative vulnerability extends beyond red blood cells to other tissues, including muscle
   • During oxidative stress episodes, muscle damage can occur, releasing CPK into circulation

3. Hemolysis-Related Secondary Effects

   • Severe hemolytic episodes can lead to systemic metabolic disturbances
   • These metabolic alterations can affect multiple organ systems, including muscle tissue 3

Clinical Presentations

G6PD deficiency with elevated CPK may present in several ways:

• Exercise-induced myoglobinuria with dark urine and elevated CPK 1
• Episodes of muscle pain and weakness during oxidative stress
• Elevated CPK following exposure to oxidative triggers (medications, fava beans, infections)

Diagnostic Considerations

When evaluating elevated CPK in patients with G6PD deficiency:

• Quantitative enzyme activity testing is recommended for diagnosing G6PD deficiency 4
• Consider the timing of testing in relation to hemolytic episodes
• Evaluate for other causes of elevated CPK (medications, trauma, exercise)
• Consider measuring the ratio of G6PD activity to other enzymes for more accurate assessment 5

Management Implications

For patients with G6PD deficiency and elevated CPK:

• Avoid medications known to trigger hemolysis, including dapsone, methylene blue, nitrofurantoin, phenazopyridine, primaquine, rasburicase, and tolonium chloride 6
• Maintain adequate hydration, especially during illness or physical exertion 4
• Monitor for signs of hemolysis and muscle damage
• Consider dietary modifications, including avoiding fava beans 4

Important Caveats

• CPK elevation may be more pronounced in certain G6PD variants, particularly the Mediterranean variant 1
• Heterozygous females may have intermediate deficiency that can still cause clinical symptoms under severe oxidative stress 4
• The relationship between G6PD deficiency and CPK elevation may be underrecognized in clinical practice
• CPK elevation may be transient and correlate with hemolytic episodes or oxidative stress

The connection between G6PD deficiency and elevated CPK highlights the systemic nature of this enzymopathy beyond its well-known hematologic manifestations, affecting multiple metabolic pathways and organ systems.