Metabolic myopathy are a large group of diseases manifested by a decrease in exercise tolerance due to metabolic disorders in muscle tissue or a lack of enzymes. Symptoms of the disease are muscle weakness, pain, cramps, paresis, difficulty performing prolonged physical activity, the formation of contractures. The diagnosis is established on the basis of anamnesis, a study of the content of enzymes in the bloodstream, a muscle biopsy. Treatment includes dietary and vitamin therapy, the use of steroids and orthopedic correction.
General information
Metabolic myopathy are an extensive group of hereditary and acquired diseases associated with metabolic disorders (glycogen, lipid fractions or ATP) in the muscles. The pathological process manifests itself in both children and adults. Hereditary forms are prone to the progression of the pathological process. The relevance of metabolic myopathy is associated with the possibility of the development of transient contractures in response to the inability of muscle tissue to use the energy potential from glucose (McArdle’s disease) or lipids (carnitine deficiency) with the breakdown of ATP. Metabolic myopathy develop in about 5 clinical cases out of 10,000.
Causes
The main cause of the development of congenital myopathies with metabolic disorders in muscle tissues is hereditary predisposition (therefore they are also called familial myopathies); the transmission of the defective gene is autosomal recessive, less often dominant or maternal. There may be random or sporadic gene mutations. The pathological process in myopathies of this kind may be associated with the pathology of ion channels of muscle membranes (familial periodic paralysis), with impaired mitochondrial function (caused by mutations in the mitochondrial genome). With glycogenoses, there is a deficiency of enzymes involved in the exchange of glycogen, followed by the accumulation of the latter in tissues, primarily in the liver and skeletal muscles. For example, in McArdle’s disease, the pathological process is associated with a deficiency of the enzyme muscle phosphorylase, as a result of which the glycolysis process necessary to provide muscles with energy is disrupted.
Acquired metabolic myopathy can be caused by endocrine diseases (hyperthyroidism, hypothyroidism, hyperaldosteronism, Cushing’s and Addison’s diseases, parathyroid hyperfunction, acromegaly, etc.), be a consequence of chronic intoxication (alcoholism, iatrogenic effects, etc.); chronic lung diseases, kidneys (uremia, chronic renal failure, electrolyte disorders), liver (liver failure) and cardiovascular system; malabsorption syndrome; vitamin D and E deficiency.
Classification
There are primary (or congenital) disorders of the metabolism of muscle tissue. This group should include diseases associated with impaired glycogen metabolism: Pompe disease, Andersen disease, Corey-Forbes disease, McArdle disease, Tauri disease, phosphorylase b kinase deficiency, FGC deficiency, phosphoglyceromutase deficiency, LDH deficiency. The group of hereditary disorders of lipid metabolism in muscles includes: carnitine deficiency, acetyl-CoA dehydrogenase deficiency and CBT deficiency. Mitochondrial myopathies are: deficiency of reductase enzymes, cytochrome b, b 1; deficiency of ATP. Disorders of purine metabolism include: deficiency of the enzyme MADA (myoadenyl deaminase).
In addition, secondary (acquired) metabolic myopathy are also isolated, which are the result of endocrine diseases or other pathological conditions of the body.
Symptoms
Disorders of glycogen and glucose metabolism. With excessive accumulation of glycogen, patients feel quite well at rest, outside of physical activity. With increased activity, enzyme deficiency prevents the formation of energy from carbohydrates. Usually, a few minutes after the start of physical work, patients begin to complain of fatigue, muscle weakness. If the intensity of the load is not reduced, muscle contracture may occur, which can develop into severe damage to muscle tissue.
In McArdle’s disease, severe muscle pain, proximal muscle hypotrophy, as well as painful compaction and muscle weakness with the subsequent development of contracture occur. The latter is caused by a violation of muscle relaxation, due to a lack of energy. Under stress, muscle breakdown may form with the development of myoglobinuria, the phenomena of severe renal failure. Possible weakness of the heart muscles with the development of heart failure.
Andersen and Cory-Forbes disease, lead to severe liver, heart, contractures; disorders of physical development in childhood, combined with moderate muscle damage.
Maltase deficiency can develop in the form of an infant form (immediately after birth) with the phenomena of muscle weakness and congestive phenomena in the heart. The disease progresses and most often leads to death; patients do not live up to 2 years. The second form of the disease begins to manifest itself in early childhood. Most often associated with respiratory disorders and pronounced weakness of the muscles of the lower extremities. The adult form of the disease is characterized by painless weakness of the muscular girdle of the upper and lower extremities and respiratory muscles.
Disorders of lipid metabolism. A greater number of neurological diseases are associated with a deficiency of lipid fractions. Some of them may manifest themselves only in a decrease in the ability to tolerate physical exertion. Carnitine deficiency and the enzyme CBT are classic examples of lipid metabolism disorders. Carnitine deficiency syndrome is manifested by progressive muscle weakness; limb muscles, as well as facial and pharyngeal muscles are affected. The CBT deficiency syndrome is characterized by bouts of pain during physical exertion. Men are most often ill, they may have pronounced muscle weakness and pain.
Mitochondrial myopathies. Limb muscles, muscle fibers of the eyeball are affected (ptosis, ophthalmoplegia). It is involved in the pathological process of the central nervous system (cerebellar ataxia, epileptic seizures, myoclonia, dementia, etc.), heart (cardiomyopathy), kidneys (tubulopathy), liver, auditory analyzer (sensorineural hearing loss). Usually children and adolescents get sick, although the pathological process may debut later. Muscle weakness is either widespread (increased fatigue, poor exercise tolerance), or more limited (local damage to the muscles of the extremities, face, or only the external muscles of the eyeball). Shortness of breath during physical exertion, headaches resembling migraines are characteristic.
Diagnostics
Diagnosis is impossible without collecting a complete anamnestic picture and a thorough clinical examination. The difficulty is due to the fact that patients do not complain at rest. Significant clinical manifestations are: severe muscle pain, weakness, convulsions, changes in urine color (myoglobinuria). The symmetry of the muscle lesion is characteristic. A thorough neurological examination is also required to identify other clinical syndromes.
A study of enzymatic activity is prescribed (blood for the enzymes CK, AST, ALT, LDH, aldolase, etc.), an ischemic test on the forearm (allows to detect glycogenoses). Electromyography or electroneurography can identify abnormalities that are characteristic of myopathies. An MRI or CT scan of the brain is prescribed in order to exclude organic changes that can also cause muscle weakness. According to the indications, a tomographic examination of the internal organs is carried out. The most significant in the diagnosis is a muscle biopsy followed by morphological, histochemical and microscopic examination (allows you to make a final diagnosis). Consultation of the following specialists is required: neurologist, cardiologist, ophthalmologist, nephrologist; with the manifestation of metabolic myopathy in early childhood – pediatric neurologist, geneticist and others.
Treatment
Treatment of congenital metabolic disorders is not possible. Only symptomatic help is used, which is expressed in diet therapy with the use of foods with a high protein content and the intake of fructose. In combination with multivitamins, this can improve the condition of patients with glycogenoses. With myoglobinuria, an additional amount of fluid is injected to maintain diuresis and prevent renal failure. In mitochondrial myopathies, medications that improve energy metabolism (L-carnitine, ubiquinone, riboflavin, thiamine, vitamins C and E) are prescribed. The use of glucocorticosteroids shows good therapeutic results. Orthopedic correction is also indicated.
In secondary or acquired myopathies, treatment is aimed at treating the underlying disease: correction of endocrine pathologies, systemic diseases, intoxications.
Prognosis and prevention
The prognosis of primary myopathies is quite unfavorable, especially for infant forms and diseases that manifest themselves from the first weeks of life. Such patients die in early childhood. Later or adult forms have a more favorable prognosis. The course and outcome of the pathological process also depends on the involvement of other organs and systems (heart, liver, kidneys, etc.). Acquired metabolic myopathy have a fairly favorable prognosis, since the main symptoms of the pathological process regress after correction of the causal disease and condition.
Prevention of primary metabolic myopathy consists in medical and genetic counseling of a couple before conception and in the first trimester of pregnancy. Timely detection and therapy of secondary myopathies helps to avoid the development of metabolic disorders in muscle tissue.