What is the significance of elevated aldolase (enzyme) levels in a lab test?

Significance of Elevated Aldolase Levels in Laboratory Testing

Elevated aldolase levels primarily indicate muscle damage or injury, and can be a valuable diagnostic marker particularly when creatine kinase (CK) levels are normal, helping identify early muscle regeneration issues or specific myopathies. 1, 2

Primary Clinical Significance of Elevated Aldolase

• Elevated aldolase serves as a marker for muscle damage, often complementary to CK testing, but can be elevated when CK remains normal 3
• Aldolase testing is particularly useful in diagnosing muscle-related disorders when CK falls within normal range 3, 2
• In myositis patients, isolated aldolase elevation may reflect immune-mediated damage of early regenerating muscle cells 2

Specific Clinical Contexts Where Aldolase Testing is Valuable

Muscle Disorders

• Aldolase elevation can predict subsequent myopathy occurrence in systemic sclerosis with higher accuracy than CK (area under ROC curve 0.80 vs 0.75) 4
• Dermatomyositis is the most common myopathy associated with selective aldolase elevation with normal CK levels 5
• Eosinophilic fasciitis often shows elevated aldolase even when peripheral eosinophilia is transient or absent 6

Distinguishing Muscle vs Liver Injury

• Aldolase testing helps differentiate between muscle injury and liver injury when liver enzymes (ALT/AST) are elevated 1
• In patients with nonalcoholic steatohepatitis (NASH) who show elevated liver enzymes, testing for aldolase can confirm whether the elevation is due to muscle injury rather than liver damage 1
• Intensive exercise (especially weight lifting) or statin therapy can cause elevations in ALT and AST due to muscle injury rather than liver damage, which aldolase testing can help confirm 1

Immune Checkpoint Inhibitor Therapy

• In patients receiving immune checkpoint inhibitor therapy, elevated aldolase along with CK can help diagnose immune-related myositis 1
• For grade 1 myositis with mild weakness, elevated CK and/or aldolase may warrant oral corticosteroid treatment 1
• Blood testing for aldolase is part of the standard workup for suspected immune-related myositis along with CK testing 1

Interpretation Considerations

• Aldolase is expressed earlier in muscle cell differentiation than CK, making it a more sensitive marker for damage to early regenerating muscle cells 2
• A cut-off value of aldolase >9 U/L (higher than the upper normal limit of 7 U/L) has been identified as predictive of subsequent myopathy development in systemic sclerosis patients 4
• Perimysial pathology (inflammation, fragmentation, vasculitis) is found in approximately 50% of patients with myopathies showing isolated aldolase elevation 5

Clinical Approach to Elevated Aldolase

• When elevated aldolase is detected, evaluate for muscle disorders even in the absence of CK elevation 3, 2
• Consider dermatomyositis, overlap myositis, and other inflammatory myopathies in the differential diagnosis 5
• In patients with NASH or those on clinical trials for liver disease, elevated transaminases with normal aldolase suggest liver injury, while elevated aldolase suggests muscle origin of enzyme elevations 1
• For patients on statins with elevated liver enzymes, aldolase testing can help determine if the elevation is due to statin-related muscle injury rather than hepatotoxicity 1

Common Pitfalls

• Relying solely on CK for diagnosing muscle disorders may miss cases where aldolase is the only elevated muscle enzyme 3, 2
• Failing to consider muscle injury as a cause of elevated liver enzymes, particularly in patients who exercise intensively or are on statins 1
• Not recognizing that isolated aldolase elevation may indicate early or specific types of muscle damage, especially in inflammatory myopathies 2, 5