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Aldolase
(Fructose-Bisphosphate Aldolase — Muscle & Liver Enzyme)
Synonyms
- Aldolase
- Fructose-1,6-bisphosphate aldolase
- ALD
- FBP Aldolase
- Aldolase A (muscle), Aldolase B (liver), Aldolase C (brain)
Units of Measurement
nkat/L, µkat/L, nmol/(s•L), µmol/(s•L), U/L, IU/L, µmol/(min•L), µmol/(h•L), µmol/(h•mL)
Description
Aldolase is a glycolytic enzyme that catalyzes the cleavage of:
Fructose-1,6-bisphosphate→Dihydroxyacetone phosphate (DHAP)+Glyceraldehyde-3-phosphate (G3P)\text{Fructose-1,6-bisphosphate} \rightarrow \text{Dihydroxyacetone phosphate (DHAP)} + \text{Glyceraldehyde-3-phosphate (G3P)}Fructose-1,6-bisphosphate→Dihydroxyacetone phosphate (DHAP)+Glyceraldehyde-3-phosphate (G3P)
It exists in three major isoforms:
- Aldolase A - Muscle (highest serum activity)
- Aldolase B - Liver
- Aldolase C - Brain
Aldolase measurement is clinically useful for:
- Muscle disorders
- Myopathies
- Dermatomyositis & polymyositis
- Muscular dystrophies
- Hepatic diseases
- Certain hematologic conditions
Physiological Role
- Key role in glycolysis
- Highly expressed in skeletal muscle, heart, liver, and brain
- Enzyme release increases with muscle damage or hepatocellular injury
- Used historically before CK testing became widespread but still valuable in myositis monitoring
Clinical Significance
Elevated Aldolase
1. Muscle Disorders
- Polymyositis
- Dermatomyositis
- Duchenne & Becker muscular dystrophy
- Inflammatory myopathies
- Rhabdomyolysis
- Post-seizure state
- Strenuous exercise
(ALT/CK may be normal while Aldolase is high in early dermatomyositis.)
2. Liver Diseases
- Acute hepatitis
- Cirrhosis
- Liver metastases
- Fatty liver (mild elevation)
3. Hemolysis-related elevations
- Hemolytic anemias (RBCs contain aldolase)
4. Malignancies
- Leukemia
- Lymphoma
- Solid tumors (variable)
Low Aldolase
Not commonly clinically significant.
Seen in:
- Late muscular dystrophy (muscle mass severely reduced)
- Advanced liver failure
- Some congenital enzyme deficiencies
Reference Intervals
(Tietz 8E + IFCC + Mayo Clinic verified; method dependent)
Typical Adult Range
- 1.0 – 7.5 U/L
- SI equivalent: 17 – 125 nkat/L
Children
Levels may be higher due to growing muscle tissue.
Note: Reference intervals vary significantly among analyzers due to substrate differences. Each lab must validate its reference range.
Diagnostic Uses
1. Myositis Evaluation
Aldolase is often elevated even when CK is normal, especially in:
- Dermatomyositis
- Overlap myositis
- Early polymyositis
2. Muscle vs Liver Differentiation
Both CK and Aldolase rise in muscle disease, whereas AST/ALT rise more in liver conditions.
Isoenzyme analysis further distinguishes Aldolase A (muscle) vs B (liver).
3. Monitoring Disease Activity
Used to monitor:
- Idiopathic inflammatory myopathies
- Muscle regeneration
- Treatment response to steroids/immunosuppressants
Isoenzymes
| Isoenzyme | Tissue Distribution | Clinical Use |
| Aldolase A | Skeletal muscle, RBCs | Myopathies, hemolysis |
| Aldolase B | Liver | Hepatitis, hereditary fructose intolerance |
| Aldolase C | Brain | Not used clinically |
Aldolase B deficiency → Hereditary fructose intolerance (HFI).
Unit Meanings
| Unit | Meaning |
| nkat/L | nanokatal per liter |
| µkat/L | microkatal per liter |
| nmol/(s•L) | nanomole per second per liter |
| µmol/(s•L) | micromole per second per liter |
| U/L or IU/L | enzyme units per liter |
| µmol/(min•L) | micromole per minute per liter |
| µmol/(h•L) | micromole per hour per liter |
| µmol/(h•mL) | micromole per hour per milliliter |
Time conversions:
- µmol/(min•L) × 60 = µmol/(h•L)
- µmol/(h•L) ÷ 1000 = µmol/(h•mL)
Analytical Notes
- Measured by kinetic enzymatic assays.
- Hemolysis falsely increases aldolase (RBC source).
- Not as specific as CK for muscle injury but more sensitive in myositis.
- Sample should be non-hemolyzed for accuracy.
Clinical Pearls
- Aldolase elevated + normal CK strongly suggests dermatomyositis.
- Persistent elevation is associated with active inflammatory muscle disease.
- Useful in pediatric myopathies where CK may be variable.
- High aldolase with signs of liver disease → consider Aldolase B contribution.
Interesting Fact
Aldolase was discovered in 1934 as one of the earliest mapped enzymes of glycolysis. Its isoenzyme patterns helped unravel tissue-specific metabolism long before CK was discovered.
References
- Tietz Clinical Chemistry and Molecular Diagnostics, 8th Edition - Enzyme Chapter.
- IFCC - Enzyme Measurement Standardization Guidelines.
- Mayo Clinic Laboratories - Aldolase, Serum Interpretation.
- ARUP Consult - Myositis Testing and Aldolase Utility.
- NIH / MedlinePlus - Muscle Enzyme Tests.
- Neurology & Rheumatology Reviews - Aldolase in Inflammatory Myopathies.