What is aldolase?

Aldolase: A Diagnostic Enzyme Marker for Muscle and Liver Disease

Aldolase is a glycolytic enzyme primarily used as a diagnostic marker for muscle disorders, with secondary utility in evaluating certain liver conditions and malignancies. It serves as an important biomarker in clinical practice, particularly when evaluating muscle injury or disease.

Definition and Biochemistry

• Aldolase (EC 4.1.2.13) is a 160 kDa enzyme that plays a crucial role in glucose metabolism by catalyzing the reversible cleavage of fructose-1,6-bisphosphate into glyceraldehyde-3-phosphate and dihydroxyacetone phosphate 1
• Three main isozymes exist:
  • Aldolase A: Predominant in muscle tissue and erythrocytes
  • Aldolase B: Predominant in liver tissue
  • Aldolase C: Predominant in brain tissue

Clinical Applications

Primary Use in Muscle Disorders

• Elevated serum aldolase (primarily A isozyme) is found in:
  • Myopathies such as progressive muscular dystrophy and polymyositis 1
  • Myocardial infarction (peaks within 24-48 hours, normalizes within 5 days) 1
  • Used alongside creatine phosphokinase (CK) to confirm muscle injury 2

Use in Immune Checkpoint Inhibitor (ICI) Therapy

• Aldolase testing is recommended in the workup of suspected immune-related myositis in patients receiving immunotherapy 2
• Blood testing for muscle inflammation should include CK and aldolase when evaluating patients with suspected myositis on ICI therapy 2
• Elevated aldolase with muscle weakness may warrant corticosteroid treatment starting at 0.5 mg/kg/day of prednisone 2

Liver Disease Applications

• Aldolase B isozyme rises significantly in acute hepatitis but only slightly in cirrhosis, chronic hepatitis, and obstructive jaundice 1
• Can help differentiate between hepatic and cardiac damage 3
• Aldolase B correlates closely with conventional biochemical markers of liver inflammation 3
• In non-alcoholic steatohepatitis (NASH) clinical trials, aldolase testing can help confirm non-hepatic origin of AST/ALT elevations when muscle injury is suspected 2

Malignancy Marker

• Aldolase A is overexpressed in numerous cancers including:
  • Hepatocellular carcinoma
  • Colorectal cancer
  • Breast cancer
  • Non-small cell lung cancer
  • Gastric cancer 4
• Serum aldolase A levels increase remarkably in patients with liver cell carcinoma and metastatic liver carcinoma 5
• However, sensitivity is not sufficient to be of clinical value as a standalone cancer marker 3

Interpretation of Results

• Normal serum aldolase A levels: approximately 171 ± 39 ng/ml 5
• Elevated levels suggest:
  1. Primary consideration: Muscle damage/disease
  2. Secondary considerations:
     • Acute hepatitis (especially aldolase B)
     • Malignancy (especially aldolase A)
     • Hemolytic anemia (due to high erythrocyte content) 1

Clinical Pearls

• When evaluating elevated liver enzymes, consider testing aldolase to help differentiate between muscle injury and true liver injury 2
• In patients with exercise-induced elevations of AST/ALT (e.g., weightlifting), aldolase testing can confirm muscle origin 2
• Statin-related muscle injury can also cause elevated liver enzymes, and aldolase testing can help confirm the muscle source 2
• Aldolase B appears to be a more sensitive marker of liver cell damage than aldolase A 3

Limitations

• Not specific enough to be used alone for cancer diagnosis 3
• Multiple conditions can cause elevations, requiring clinical correlation
• Not routinely included in standard liver function panels or muscle enzyme panels

Aldolase testing should be considered when evaluating patients with suspected muscle disorders, when differentiating between muscle and liver sources of enzyme elevations, and as part of a comprehensive evaluation of certain malignancies.