What are the causes of elevated aldolase levels beyond muscle damage?

Causes of Elevated Aldolase Beyond Muscle Damage

Elevated serum aldolase levels can be caused by various conditions beyond muscle damage, including liver diseases, malignancies, hemolytic disorders, and certain inflammatory conditions.

Primary Causes of Elevated Aldolase

Liver Disorders

• Acute hepatitis causes significant elevation of aldolase, particularly the B isozyme 1
• Fulminant hepatitis shows remarkable increases in serum aldolase A levels 2
• Liver cell carcinoma and metastatic liver carcinoma consistently show elevated aldolase A levels 2
• Cirrhosis, chronic hepatitis, and obstructive jaundice cause mild aldolase elevations 1

Inflammatory and Autoimmune Conditions

• Dermatomyositis can present with isolated aldolase elevation despite normal creatine kinase (CK) levels 3
• Overlap myositis shows selective aldolase elevation in some cases 3
• Eosinophilic fasciitis frequently presents with elevated aldolase (11 out of 12 patients in one study) even when other inflammatory markers are normal 4
• Immune-mediated myopathy with perimysial pathology may show isolated aldolase elevation 3

Hematologic Disorders

• Hemolytic anemia causes elevated aldolase due to the high concentration of the enzyme in erythrocytes 1
• Multiple blood transfusions can lead to increased aldolase levels 5

Cardiac Conditions

• Myocardial infarction causes aldolase elevation that peaks within 24-48 hours and normalizes within five days 1

Malignancies

• Various malignant tumors can cause elevated aldolase levels, with isozyme A predominating in serum 1
• Primary liver cell carcinoma shows increased aldolase A levels more frequently than alpha-fetoprotein elevations 2

Clinical Significance and Diagnostic Considerations

Distinguishing Features

• In muscular diseases, aldolase A isozyme is predominantly elevated 1
• In liver diseases, particularly acute hepatitis, aldolase B isozyme shows significant elevation 1
• Isolated aldolase elevation with normal CK may indicate early regenerating muscle damage rather than established myopathy 6

Diagnostic Value

• Testing for blood levels of creatine phosphokinase (CK), aldolase, or other muscle-related enzymes can help confirm the non-hepatic origin of liver enzyme elevations 5
• Aldolase elevation may be a more sensitive marker than peripheral eosinophilia or elevated ESR in conditions like eosinophilic fasciitis 4
• In patients with nonalcoholic steatohepatitis (NASH), intensive exercising can lead to acute elevation in AST and ALT due to muscle injury, which can be confirmed by testing aldolase levels 5

Clinical Pitfalls and Considerations

• Aldolase elevation may be the only abnormal finding in early or treated inflammatory myopathies 3
• Dermatomyositis with isolated aldolase elevation may have different clinical features compared to cases with elevated CK, including less frequent cutaneous involvement 3
• When evaluating liver function test abnormalities, consider testing aldolase to differentiate between hepatic and non-hepatic causes of enzyme elevations 5
• In glycogen storage diseases, elevated aldolase may be present alongside other enzyme abnormalities and should be considered in the differential diagnosis 5

Monitoring and Management Implications

• Aldolase may be useful for monitoring disease activity in conditions like eosinophilic fasciitis, particularly after treatment initiation 4
• In clinical trials, especially for NASH patients, aldolase testing can help differentiate between drug-induced liver injury and muscle-related causes of enzyme elevations 5
• The pattern of aldolase isozyme elevation (A vs B) can provide clues about the tissue origin of the enzyme increase 1, 2