Aldolase: A Myositis Biomarker
The month of May is devoted to myositis awareness, a muscle-wasting disease resulting in reduced muscle strength and fatigue. The term ‘myositis’ is an umbrella term referring to the “general inflammation or swelling of the muscle”. However, myositis is more often referred to as a disease involving chronic inflammation of the muscles which does not improve with rest. This condition is also known as idiopathic inflammatory myopathy (IIM) 1.
Myositis is an autoimmune disease characterised by pain, muscle weaknesses, swelling and extreme fatigue which often gradually appear. Myositis can be potentially life-threatening, especially dermatomyositis which affects the heart muscle and lungs. Whilst a rare disease, it is estimated that 75,000 Americans suffer from myositis, however, many are undiagnosed or misdiagnosed with more common autoimmune diseases. Most physicians are unfamiliar with the disease and symptoms and so the consequences of this can be catastrophic in terms of long-term physical muscle damage, disability and even death 1, 2, 3.
Table 1 reviews the different forms of myositis
Table 2 reviews complications with or due to myositis
It is vital that physicians are educated to include myositis despite it being a rare disease as it is essential that myositis patients are diagnosed quickly to ensure appropriate treatment plans are implemented.
Aldolase testing has been recognised as a marker in the differential diagnosis of muscle weakness as aldolase levels remain consistent where weakness is caused by neurological problems such as multiple sclerosis (MS). Aldolase is an enzyme specifically found in skeletal muscle and the liver. When either the muscle or liver are damaged, aldolase is released into the bloodstream 13 . A few studies support aldolase testing in the diagnosis of myositis:
1. Arthritis Research & Therapy (2012): Aldolase predicts subsequent myopathy occurrence in systemic sclerosis 14
A French monocentric 4-year study prospectively evaluated n=137 systemic sclerosis (SSc) patients without proximal muscle weakness to assess the risk of myopathy related systemic sclerosis (Myo-SSc) according to the European Neuro Muscular Centre criteria. Aldolase, creatine kinase (CK), C-reactive protein (CRP), alanine transaminase (ALT) and aspartate transaminase (AST) were evaluated.
Aldolase is a valuable diagnostic tool in the identification of SSc patients at a high risk of developing subsequent Myo-SSc. This enables clinicians to monitor at-risk patients as well as identifying Myo-SSc in its earliest stages, enabling the effective and swift implementation of an appropriate treatment plan when the muscle damage is still in a reversible stage.
2. Clinical and Experimental Rheumatology (2013): Isolated elevation of aldolase in the serum of myositis patients: a potential biomarker of damaged early regenerating muscle cells 15
The in vitro analysis of the gene and protein expression levels of aldolase and CK during muscle cell differentiation.
Aldolase A is expressed in the absence of CK in undifferentiated muscle cells and in the early differentiation process. Isolated elevated serum aldolase A in myositis patients reflects preferential immune-mediated damage of early regenerative cells. Aldolase is a biomarker of damaged early regenerating muscle cells.
Myositis can be a potentially life-threatening disease when undiagnosed or misdiagnosed. Aldolase is recognised as a biomarker in the diagnosis and monitoring of myositis. Randox are one of the only in-vitro diagnostic manufacturers to offer the aldolase assay in an automated and manual biochemistry format. Not only does the Randox methodology have an excellent correlation coefficient to r=0.9917 when compared against standard methods, the Randox assay is lyophilised for enhanced stability with an excellent measuring range of 1.73 – 106U/l. Moreover, applications are available detailing instrument-specific settings for the convenient use of the Randox aldolase assay on a wide range of clinical chemistry analysers.
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Clinical Chemistry Panel
 The Myositis Association. About Myositis. [Online] [Cited: May 3, 2019.] https://www.myositis.org/about-myositis/.
 Kobert, Linda. Myositis, a rare muscular inflammatory disease that ofen goes undiagnosed or misdiagnosed, disproportionally impacts women of color. s.l. : The Myositis Organisation.
 Muscular Dystophy UK. Myositis. [Online] [Cited: May 6, 2019.] https://www.musculardystrophyuk.org/about-muscle-wasting-conditions/myositis/.
 The Myositis Association. Types of Myositis. [Online] [Cited: May 3, 2019.] https://www.myositis.org/about-myositis/types-of-myositis/.
 —. Sporadic Inclusion Body Myositis. [Online] [Cited: May 3, 2019.] https://www.myositis.org/about-myositis/types-of-myositis/sporadic-inclusion-body-myositis/.
 —. Dermatomyositis. [Online] [Cited: May 3, 2019.] https://www.myositis.org/about-myositis/types-of-myositis/dermatomyositis/.
 —. Polymyositis. [Online] [Cited: May 3, 2019.] https://www.myositis.org/about-myositis/types-of-myositis/polymyositis/.
 —. Necrotizing Myopathy. [Online] [Cited: May 3, 2019.] https://www.myositis.org/about-myositis/types-of-myositis/necrotizing-myopathy/.
 —. Juvenile Myositis. [Online] [Cited: May 3, 2019.] https://www.myositis.org/about-myositis/types-of-myositis/juvenile-myositis/.
 —. Cancer-associated myositis. [Online] [Cited: May 3, 2019.] https://www.myositis.org/about-myositis/complications/cancer-associated-myositis/.
 —. Infection. [Online] [Cited: May 3, 2019.] https://www.myositis.org/about-myositis/complications/infection/.
 —. Cardiovascular Disease. [Online] [Cited: May 3, 2019.] https://www.myositis.org/about-myositis/complications/cardiovascular-disease/.
 —. Blood Tests. [Online] [Cited: May 3, 2019.] https://www.myositis.org/about-myositis/diagnosis/blood-tests/.
 Aldolase predicts subsequent myopathy occurrrence in systemic sclerosis. Tolédano, Cécile, et al. Faubourg Saint-Antoine : Arthritis Research & Therapy, 2012.
 Isolated elevation of aldolase in the serum of myositis patients: a potential biomarker of damaged early regenerating muscle cells. Casciola-Rosen, Livia, et al. Baltimore : Clinical and Experimental Rheumatology, 2013.
Reagents | Zinc, Copper & Aldolase
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Randox offer an extensive range of 115 third party diagnostic reagents which are internationally recognised as being of the highest quality; producing accurate and precise results. Continually reinvesting in R&D, Randox continue to offer the opportunity to expand your test menu without expanding your lab. Not only does Randox offer superior performance assays, but also niche assays, meaning that Randox are one of the only manufacturers to offer the test in an automated biochemistry format.
A niche assay from Randox meaning that Randox are one of the only manufacturers to offer a clinical chemistry zinc assay
Strong correlation with standard methods as the Randox zinc assay showed a correlation coefficient of r=0.9946 when compared against standard methods
A measuring range of 11.3 – 159 µmol/l for the comfortable and accurate detection of abnormal levels
Liquid ready-to-use reagents for convenience and ease-of-use
Stable to expiry date when stored at +15 to +25°C
Applications are available detailing instrument-specific settings for the convenient use of the Randox zinc assay on a wide range of clinical chemistry analysers
An essential trace metal and the only metal present in all enzyme classes, zinc is the second most abundant micronutrient in humans after iron. Zinc is required for a healthy immune system, a healthy growth rate during pregnancy, childhood and adolescence, wound health and synthesizing DNA. Zinc can modulate brain excitability and is vital in the synaptic plasticity of the brain which is thought to contribute towards memory and learning. Zinc has also been identified as a neurotoxin which suggests that zinc homeostasis is involved in the normal functioning of the central nervous system and the brain 1.
Zinc deficiency is identified as a malnutrition problem worldwide, especially in areas of high cereal intake and low animal food intake. However, other factors may contribute to low zinc levels including: the bioavailability of zinc, chronic illnesses such as diabetes, malignancy, hepatic disease and sickle cell disease. Higher zinc requirements have been identified in infants, children, adolescents, and pregnant and lactating women compared to adults. During periods of growth, zinc deficiency can result in growth failure. The most common organs affected by zinc deficiency clinically include: central nervous system, gastrointestinal, epidermal, skeletal, immune, and reproductive systems 2 3.
A niche assay from Randox meaning that Randox are one of the only manufacturers to offer a clinical chemistry copper assay
Exceptional correlation with standard methods as the Randox copper assay showed a correlation coefficient of r=0.99 when compared against standard methods
A wide measuring range of 6.6 – 86 µmol/l for the comfortable and accurate detection of abnormal levels
Lyophilised reagents for enhanced stability
Excellent stability of 2 weeks when stored at +2 to +8°C
Applications are available detailing instrument-specific settings for the convenient use of the Randox copper assay on a wide range of clinical chemistry analysers
An essential trace metal, copper is the third most abundant micronutrient in humans after iron and zinc. Copper is mainly found in the brain, liver, kidneys, heart and skeletal muscle with the highest quantities found in the liver and muscles. It aids in some of the key bodily functions including: the production of red blood cells, the maintenance of nerve cells and the immune system, the formation of collagen to absorb iron for energy production, and the formation of melanin, bone and connective tissue. Ceruloplasmin is the protein responsible for the transportation of copper around the body 4.
There are various health problems that can cause abnormal copper levels, however deficiency is less likely than toxicity because a normal diet contains plenty of copper including: organic meats, beans and wholegrains. Deficiency is more likely to occur in those who are malnourished, more likely children.
Deficiency more commonly occurs in premature babies, resulting in bone abnormalities and fractures. Menkes Disease is a rare inherited genetic disorder of copper metabolism and is characterised by sparse and kinky hair as children with this disorder are unable to absorb enough copper 5.
Toxicity can be caused by consuming too many dietary supplements high in copper, from drinking contaminated water, or from fungicides containing copper sulphates. Wilson disease is a rare inherited disorder that prohibits the liver from safely storing and excreting copper resulting in it seeping out of the liver and building up in the eyes, liver, kidneys and brain causing nerve damage, and if untreated, it can be fatal 6.
A niche assay from Randox meaning that Randox are one of the only manufacturers to offer a clinical chemistry aldolase assay
Excellent correlation coefficient of r=0.9917 when compared against other commercially available methods
A wide measuring range of 1.73 – 106 µmol/l for the comfortable and accurate detection of abnormal levels
Lyophilised reagents for enhanced stability
Applications are available detailing instrument-specific settings for the convenient use of the Randox aldolase assay on a wide range of clinical chemistry analysers
There are three types of Aldolase enzymes that can be can be found throughout the body: A, B and C. It is responsible for converting glucose into energy.
A is primarily contained within the muscle and erythrocytes, whereas B is contained within the liver, enterocytes and kidney, and A and C can be found within the brain. Despite the Aldolase enzyme existing throughout the body, the highest concentration levels of it can be found in the liver and the skeletal muscle, although testing this enzyme is routinely used for skeletal muscle damage 7.
Elevated levels of type A aldolase in the blood can be found in patients with damage to the skeletal muscle as the result of a trauma which includes dermatpmyositis, infectious mononucleosis, muscular dystrophy, myocardial infarction, hepatic cancer due to the damaged cells triggering the release of A into the blood. On the other hand, the concentration levels of A in the blood remain normal in situations where weakness is caused as the result of a neurological disease such as multiple sclerosis. Measuring A concentration levels in the blood can therefore be used to determine the root cause of muscle weakness, whether muscle trauma or neurological myopathy, in patients 7.
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 Osredkar, Josko and Sustar, Natasa. Copper and Zinc, Biological Role and Significance of Copper/Zinc Imbalance. 1, s.l. : Journal of Clinical Toxicology, 2011, Vol. 3.
 Jockers, Dr. David. How To Test Zinc Levels At Home. DrJockers.com. [Online] 2019. [Cited: November 28, 2018.] https://drjockers.com/test-zinc-levels-home/..
 Roohani, Nazanin, et al. Zinc and its importance for human health: An integrative review. National Center for Biotechnology Information. [Online] J Res Med Sci, February 18, 2013. [Cited: November 28, 2018.] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3724376/..
 Nordqvist, Joseph. What are the health benefits of zinc? Medical News Today. [Online] December 5, 2017. [Cited: November 28, 2018.] https://www.medicalnewstoday.com/articles/263176.php.
 Macfarlane, Susan. Understanding Nutrient Ratios: Zinc/Copper. Susan Macfarlane. [Online] October 29, 2017. [Cited: November 28, 2018.] https://susanmacfarlanenutrition.com/understanding-nutrient-ratios-zinccopper/.
 National Center for Advancing Translational Sciences. Menkes disease. National Center for Advancing Translational Sciences. [Online] Genetic and Rare Disease Information Center, April 7, 2017. [Cited: November 30, 2018.] https://rarediseases.info.nih.gov/diseases/1521/menkes-disease.
 Berridge, Brian R, Van Vleet, John F and Herman, Eugene. Chapter 46 – Cardiac, Vascular, and Skeletal Muscle Systems. 2013.
The Randox Acusera Aldolase control is specifically designed to monitor the accuracy and precision of Aldolase assays on a wide range of clinical chemistry instruments.
Features & Benefits
- Lyophilised for enhanced stability
- Human based serum
- Stable to expiry date at 2°C – 8°C
- Reconstituted stability of 5 days at 2°C – 8°C