Background

Aldolase is a part of a fructose and glucose metabolism process. It is a cytoplasmic enzyme. It converts fructose 1,6-biphosphate into glyceraldehyde 3-phosphate and dihydroxyacetone phosphate (DHAP).

This enzyme catalyzes 6 reversible reactions in glycolysis and gluconeogenesis. In glycolysis, it converts fructose 1,6-bisphosphate to phosphoenolpyruvate by an oxidative process. In gluconeogenesis, it converts phosphoenolpyruvate to fructose 1,6-bisphosphate by reduction process. It also cleaves into fructose 1-phosphate to dihydroxyacetone phosphate and glyceraldehyde.

Aldolase A presents in the erythrocytes and muscle. Aldolase B presents in enterocytes, kidney, and liver. Aldolase A and aldolase C present in the brain. Aldolase B focuses on glycolysis and gluconeogenesis. Aldolase A and C focus on glycolysis process.

Indications/Applications

To produce more energy as an increased demand, glycolysis process upregulated by the cancer cells. As per the recent study, aldolase A function was studied. Level of mRNA expression of aldolase A was increased in colon cancer tissues. Increased level of aldolase A expression linked to the metastasis and progression of the colon cancer.

Improper functioning of the aldolase B can lead to the genetic disease like hereditary fructose intolerance (HFI). It leads to improper functioning of fructose-1-phosphate (F1P). Body tissue accumulate F1P which produce toxicity. As a result, phosphate remains in an unstable state, which cannot produce a phosphate chain. This leads to the low level of phosphate and low ATP production and storage. This causes suppression in the glycogenolysis process in the liver and leads to the hypoglycemia.

The gluconeogenesis process is also affected by the accumulation of F1P. It reduces the availability of the glucose. Hepatic and renal damage and inhibition of synthesis of protein is caused by the loss of ATP. To live with the symptoms free, one should avoid foods which contain fructose, sucrose, and sorbitol.

Autosomal recessive mutations affect the A149P allele. This provides the base to classify the disease.

Aldolase test is performed to diagnose myopathies like:

Inflammatory muscle diseases like dermatomyositis and polymyositis

Muscular dystrophy

Rhabdomyolysis

Muscle problems because of the use of certain medications

Weakness and muscle pain because of the infectious diseases

The symptoms which are associated with the myopathy diseases are like:

Muscle pain known as myalgia

Weakness in muscle

Stiffness

Cramps

Spasms

Clinical Significance:

With age, aldolase level may vary. Newborns have higher level of aldolase and as the adulthood arrives, it decreases. Normal values also depend on the how the lab is conducting the tests. Fasting for less than 8 hours and certain medications may also lead to false positive result. Increased serum level of aldolase may be a sign of a damage to many organs system.

As the cardiac enzyme panel and liver function tests introduced, aldolase test is no longer ordered as a routine to assess the function of the liver or heart. Aldolase A level may be used to determine the basic causes of the neurological myopathy vs muscle symptoms.

Reference Range

The normal value of aldolase in adult is 3 to 8.2 Sibley-Lehninger units/dL or in SI units, it is 22 to 59 mU/L at 37 °C.

In newborn, aldolase level is approximately 4 times higher than the adult values and in children, it is 2 times higher than the adult values.

Interpretation

An aldolase test is used to assess any injury present in the organs like liver, muscle, heart, or kidney. Aldolase level measures in U/L and the range is between 1.0 to 16.0. The normal values are change between males and females on the basis of weight, height, muscle mass, and the laboratory methods.

Increased level of aldolase is associated with the conditions like skeletal muscle damage (trauma), polymyositis, dermatomyositis, muscular dystrophy, infectious mononucleosis, no spherocytic hemolytic anemia, myocardial infarction, auto or viral immune hepatitis cancer, pancreatic cancer, colon cancer, osteosarcoma, and prostate cancer.

To interpret the result accurately, it is necessary to understand the subtypes of aldolase. When any damage occurs to the cells which contains aldolase, aldolase releases in the blood at an increased level. Assessing the aldolase can guide to the treatment therapy. As an example, Aldolase A is present in the muscle tissue, and it is used to assess the muscular dystrophy.

Aldolase A level may be used to determine the basic causes of the neurological myopathy vs muscle symptoms. If the aldolase A level is increased, it is because of the inflammation of the muscle. If the aldolase A level is not increased, the secondary cause is related to the pathology. As an example, patients who has a history of multiple sclerosis have muscle weakness but has a normal level of aldolase A.

An increased level of aldolase B is associated with the heart or liver disease like myocardial infraction. This marker is not used as there are many other tests have more specificity for the heart and liver diseases like liver function test (LFT) and cardiac enzymes panel.

Collection And Panels

Serum aldolase test

Sample type: Blood

Sample collection method: Routine venipuncture

Sample collection container: Red top tube (no gel tube, plain tube)

Sample volume: 3.0 ml blood, minimum 0.2 ml for testing

Unacceptable samples: Hemolyzed samples and samples in serum gel tubes are unacceptable.

Considerations: Before the collection of samples, fast for at least 8 hours and avoid any intense physical activity. No fasting or intense physical activity may cause breakdown of the muscles. It leads to the falsely increased aldolase level and false positive result. This test assesses the total enzyme activity. It can not measure the specific activity of aldolase A, B, or C.

Panels: This test is performed separate from the other blood test panels.

Other tests may be performed to assess the liver function damage are AST (aspartate aminotransferase) test and ALT (alanine aminotransferase) test. Other tests may be performed to assess the muscle cell damage are LDH (lactate dehydrogenase) test and CPK (creatine phosphokinase) test.

Modifying factors: Certain medications like statin and steroid may lead to the falsely increased level of aldolase. One should stop taking the medications before the test, as per the information provided by the healthcare provider.

References

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115481/