McArdle’s disease is an energy utilization disorder with a genetic cause. Affected individuals suffer from dark urine, muscle weakness, cramps, and skeletal muscle stiffness. To date, McArdle’s disease is incurable and is treated only symptomatically with dietary and physical therapies.
What is McArdle disease?
McArdle disease is also known as McArdle myopathy, McArdle disease, or McArdle syndrome. Sometimes the energy utilization disorder is also referred to as glycogen storage disease type V. The namesake of McArdle’s disease is its first describer, Brian McArdle. The pediatrician first documented a defect in alpha-glucan phosphorylase in 1951. This is the isoform of the enzyme glycogen phosphorylase. This enzyme is found specifically in human skeletal muscle, where it is responsible for glucose utilization. A genetic defect can impair the activity of glycogen phosphorylase and thus trigger an energy utilization disorder. The body stores the energy carrier glucose in the muscles in the form of glycogen. Glycogen phophorylase recycles glycogen back into glucose residues. Thus, the enzyme provides the body with material for energy production during glycolysis or the oxidative citrate cycle. In McArdle disease, this supply process is impaired.
Causes
McArdle disease results from a genetic defect and is a relatively rare inherited disorder. The genetic enzyme defect interferes with the deprotection of glycogen to glucose. As a result, glycogen accumulates and the organism is no longer supplied with sufficient energy. The term PGYM mutation is often used in connection with McArdle’s disease. McArdle’s disease is passed on in an autosomal recessive inheritance. Thus, only the offspring of two carriers of the genetic defect can suffer from the phenomenon. The probability of this is one in four for two gene defect carriers. However, the probability is just as high for a healthy child. The probability of a symptomless child with an annexation of the genetic defect is estimated at a ratio of about two to four.
Symptoms, complaints, and signs
McArdle syndrome usually becomes apparent at an early age in the form of fatigue and exhaustion. Symptoms appear in clusters no later than young adulthood. The energy utilization disorder is most noticeable in the skeletal muscles. Reduced muscle resilience, muscle cramps, stiffness and muscle pain are among the most common early symptoms. Many patients also report a dark discoloration of the urine. This discoloration is usually due to muscle breakdown products in the context of increasingly severe muscle damage. The symptoms described usually occur after extreme exercise or during prolonged muscular exertion such as hiking. Patients with McArdle’s disease therefore do not have to be permanently affected by the symptoms of the disease. The symptoms usually subside. There is often an improvement after about ten minutes. This improvement is related to the change in the muscle’s own energy metabolism. Even short breaks often cause the symptoms to recede momentarily.
Diagnosis and course of the disease
Establishing a diagnosis for McArdle disease is challenging. Anamnestic muscle strain pain is the primary factor. This pain can be assessed in more detail using a muscle stress test. However, they are extremely non-specific and therefore not really a sufficient indication of McArdle’s disease. In the serum, patients with this hereditary disease often show an elevated creatine kinase. Elevated uric acid and ammonia levels may also be pathological and indicative of McArdle’s disease. However, these factors are also rather nonspecific and also occur in other enzyme disorders. Therefore, when McArdle’s disease is suspected, a physician usually orders a muscle biopsy. In this biopsy, the detection of glycogen deposits in the muscle fibers is considered diagnostic. Enzyme histochemistry supports the diagnosis by the presence of unreactive or barely reactive phosphorylase. Molecular genetic studies can detect a PGYM mutation. The prognosis of McArdle’s disease is favorable. For example, the disease is not associated with a markedly reduced life expectancy.
Complications
As a result of McArdle’s disease, in most cases, affected individuals suffer from very pronounced fatigue and exhaustion. The patient’s ability to cope with stress also decreases significantly, resulting in fatigue and, not infrequently, exclusion from social life. Cramps also occur in the muscles and the affected person appears stiff and immobile. The muscles themselves can also hurt, leading to various restrictions in everyday life. It is not uncommon for the pain to occur at night in the form of pain at rest, leading to sleep problems. Pain and swelling occur especially during heavy exertion. However, the complaints themselves do not occur permanently and disappear after a short time. However, the patient’s quality of life is significantly reduced by the permanent pain caused by exertion. However, life expectancy is not limited by McArdle’s disease. The symptoms can be treated and limited with various therapies and training. There are no particular complications. However, a causal treatment of this disease is not possible.
When should one go to the doctor?
As a rarely occurring glycogen storage disease, McArdle’s disease is rarely correctly diagnosed before the age of 30. The metabolic disease glycogenosis type 5 is mainly manifested by muscle pain. These occur even with mild and short exercise intensity. These symptoms of McArdle’s disease are not infrequently underestimated or misinterpreted by sufferers or medical professionals. Sufferers often treat such muscle problems by resting or giving magnesium. Even if sufferers go to the doctor in time, this often does them no good. If the disease progresses untreated, the muscular problems increase. Cramps, myalgias or severe muscular fatigue occur. Many muscle cells are now destroyed by the glycogen storage problems. So far, only symptomatic treatment of McArdle’s disease is feasible. Before athletic exertion, ketogenic nutrition can have a symptom-relieving effect. With endurance training the individual load limit is maintained. Without special knowledge about the nature of the disease, patients can hardly behave properly. More than a relief of symptoms can not be achieved even with a known diagnosis and medical or physiotherapeutic treatment.
Treatment and therapy
The cause of McArdle’s disease cannot be cured to date. Therefore, only symptomatic therapies are available for treatment to date. These include, first and foremost, a dietary approach. Patients should actively ingest glucose and fructose, especially shortly before or during periods of exertion. This measure is usually combined with exercise therapies. In this way, permanent muscle weakness can possibly be reduced by physiotherapeutic measures in conjunction with the dietary measures. In this context, the anaerobic threshold plays an important role. Endurance training below this threshold has been shown by studies to produce the best results. The anaerobic threshold is the balance between the breakdown and formation of lactate. Endurance training should therefore take place below the maximum load intensity as a therapeutic measure in McArdle’s disease. In individual cases, drug therapies are also used as a therapeutic measure. These include, above all, the administration of low-dose creatine. This drug treatment has led to a significant improvement in performance for patients in clinical studies. Because gene therapy is highly valued in modern research, it may be possible to develop a causative treatment option for McArdle disease within the next few decades.
Outlook and prognosis
The life expectancy of affected individuals with McArdle disease is not limited. Due to the disease, patients suffer in most of the cases from very pronounced fatigue and permanent exhaustion. The resilience of those affected also drops significantly and there is often a feeling of exhaustion. Not infrequently, this leads to a downright exclusion from everyday social life. Muscle cramps can also occur, making patients appear very stiff and unnaturally immobile. The muscles themselves can also be very painful and thus lead to various restrictions in the patient’s everyday life.Often, this pain also occurs during sleep at night. In the form of pain at rest, they often lead to severe sleep complaints. Particularly with very strong loads it comes to swellings and pains with the ill ones. However, these complaints do not occur permanently. Often they disappear again after a short time as if by itself. However, the patients’ quality of life is significantly reduced by the permanent pain caused by exertion. The complaints can, however, be treated and slowed down. This is done with the help of various therapies and special training. In McArdle’s disease, there are no complications worth mentioning. However, a complete cure of the disease is not possible.
Prevention
McArdle disease cannot be prevented because it is an automal recessive inherited disease.
Follow-up care
As a rule, follow-up care for McArdle’s disease proves to be relatively difficult, with very few, if any, specific measures of follow-up care available to the affected individual in some cases. Since it is a genetic disease, there is no complete cure. Affected individuals should therefore undergo genetic testing and counseling if they wish to have children, in order to better assess the risk of passing on the disease to offspring. As a rule, those affected by this disease are dependent on the help and care of their own family, whereby loving and intensive conversations are also very important. This can prevent depression and other psychological upsets. Likewise, the measures of physiotherapy or physiotherapy are very important to alleviate and limit the symptoms of McArdle’s disease. The affected person can also repeat many exercises from such therapies at home and thereby increase mobility. In many cases of McArdle’s disease, contact with other people affected by the disease is also very useful, as it can lead to an exchange of information, which can facilitate the everyday life of the affected person. As a rule, the patient’s life expectancy from this disease remains unchanged.
This is what you can do yourself
Dietary measures are in the foreground of the therapy. The patient must pay attention to a healthy diet rich in glucose or fructose. Especially shortly before or during physical exertion, the healing process can be positively influenced by the intake of the corresponding substances. In addition, alcohol and caffeine should be avoided. Ideally, the diet plan is drawn up together with the responsible physician and a nutrition expert. Since McArdle’s disease predominantly affects the muscles, sports should be practiced. Endurance training below the anaerobic threshold can significantly improve performance. In combination with creatine treatment, muscle symptoms can be effectively reduced. Other self-help measures focus on a healthy lifestyle with sufficient exercise, a balanced diet and the avoidance of stress. Physical stress in particular should be avoided, as this can quickly lead to a worsening of symptoms. Patients who experience severe muscle discomfort despite the above measures are best advised to speak to the doctor in charge. Often the creatine therapy must be readjusted or supplemented with other preparations. Alternative measures such as massage or acupuncture can also help in individual cases of McArdle’s disease.
