Health, medicine, healthy lifestyle. Congenital myopathy Myopathy in a child symptoms

Owners of patent RU 2400221:

The invention relates to medicine, in particular psychoneurology, and concerns the treatment of congenital structural myopathies and muscular dystrophies. For this purpose, energy tropic therapy is carried out, consisting of the administration of L-carnitine at a dose of 20-30 mg/kg/day, coenzyme Q10 at a dose of 60-90 mg/day, succinic acid - 200 mg/day, citric acid - 50 mg/kg per day. day, vitamin B1 - 100 mg/kg per day, vitamin B6 - 200 mg per day, vitamin B12 - 200 mg/day for two months, twice with a break of two months. This complex of drug therapy, including the administration of high doses of coenzyme Q10, in combination with the developed administration regimen, provides an increase in motor activity in children suffering from structural myopathies and congenital muscular dystrophies, due to a complex effect on various parts of mitochondrial metabolism. 7 ill.

The invention relates to medicine, in particular psychoneurology. The work is based on the idea of ​​the feasibility of using energotropic therapy to correct mitochondrial changes for the treatment of congenital structural myopathies and congenital muscular dystrophies.

Congenital structural myopathies are a heterogeneous group of genetically determined diseases with different types of inheritance and a variety of course options. Common manifestations of congenital structural myopathies are early onset (from birth or from the first months of life), generalized muscle hypotonia, decreased or absent tendon reflexes, muscle atrophy and structural skeletal abnormalities.

Congenital structural myopathies include “central core” disease, “multiple central core” disease, nemaline myopathy, centronuclear myopathy, congenital myopathy with disproportion of muscle fiber types, congenital myopathy with intracytoplasmic inclusions in the form of reduced bodies, myopathy with accumulation of bodies similar to fingerprints fingers, sarcotubular myopathy.

Congenital muscular dystrophies are a heterogeneous group of hereditary neuromuscular diseases, which are characterized by congenital muscle hypotonia and muscle weakness, multiple symmetric contractures of large joints and a progressive course. A characteristic morphological feature of the damaged muscle is dystrophic changes, atrophy and replacement with connective tissue.

All known forms of congenital muscular dystrophy are characterized by their onset at birth with a symptom complex of a “flaccid” child, including generalized muscle hypotonia, decreased deep tendon reflexes, delayed motor development, muscle atrophy, structural deformations of the skeleton, and multiple joint contractures.

Since a diagnosis that specifies the form cannot be reliably made clinically for congenital myopathies, an incisional biopsy of muscle tissue is performed, followed by morphological, histochemical and electron microscopic examination of the resulting biopsy.

Not only diagnosis, but also treatment, care, and social adaptation of patients with congenital structural myopathies present significant difficulties. The severe course, the presence of complications from the heart and skeletal deformities, the risk of re-birth in a family of a sick child, the lack of effective methods of therapy make the issues of diagnosis, determination of criteria for prognosis of the course of these diseases, and especially the introduction of new corrective therapy regimens extremely urgent.

In recent years, the Moscow Research Institute of Pediatrics and Pediatric Surgery has been the first in the world to describe mitochondrial changes in children with congenital structural myopathies and congenital muscular dystrophies and to conclude that these changes are compensatory.

In a morphological study of muscle biopsies from patients with congenital myopathies, the authors identified mitochondrial disorders in the form of an increase in the number of mitochondria in myons, changes in histochemical activity in myons, and the appearance of the RRF phenomenon.

The purpose of the invention is to develop a new method for the treatment of congenital myopathies in children by correcting secondary mitochondrial deficiency.

This goal is achieved by using drugs that normalize energy metabolism (Kazantseva L.Z., Yuryeva E.A., Nikolaeva E.A., etc. Basic methods of treating children suffering from mitochondrial diseases. Guidelines No. 99/160. M.: Ministry of Health RF, 2001, Materials of the 5 European Meeting on mitochondrial Pathology: Italy 2001. Mitochondrion 2001).

Drugs that normalize energy metabolism include:

L-carnitine - is an activator of fatty acid metabolism; transports fatty acids across the membrane from the cytoplasm into the mitochondria, where these acids undergo a process of beta-oxidation to produce large amounts of metabolic energy in the form of ATP.

Coenzyme Q10 - activates the transfer of electrons in the respiratory chain, yantavit is a powerful antioxidant, an intensive supplier of electrons in the respiratory chain, supports calcium transport.

Vitamin B complex (thiamine, pyridoxine, cyanocobalamin).

Thiamine (vitamin B1) - as a result of phosphorylation processes, it is converted into cocarboxylase, which is a coenzyme in many enzymatic reactions in carbohydrate, protein and fat metabolism.

Pyridoxine (vitamin B6) is necessary for the normal functioning of the central and peripheral nervous system, and in its phosphorylated form it is a coenzyme in the metabolism of amino acids.

Cyanocobalamin (vitamin B12) - participates in a number of biochemical reactions that ensure the vital functions of the body - the transfer of methyl groups, the synthesis of nucleic acids, proteins, the metabolism of amino acids, carbohydrates, lipids.

Succinic acid is a powerful antioxidant, an intensive supplier of electrons in the respiratory chain, and supports calcium transport. These effects are enhanced by the catecholamine-mimetic, antitoxic, hepatoprotective, and anti-ketogenic effects of succinic acid.

Citric acid is a necessary link in the system of biochemical reactions of cellular respiration, taking part in the tricarboxylic acid cycle. Citric acid is found in small quantities in the mitochondria of all cells, has metabolic, antihypoxic and antioxidant properties, stimulates redox reactions, respiration processes and ATP synthesis. Another function of citric acid is to maintain acid-base balance and ionic composition in the body. The intake of succinic and citric acids was ensured by the administration of lemontar.

The method for correcting mitochondrial deficiency in children with congenital myopathies has no analogues, since mitochondrial deficiency in congenital myopathies was described for the first time.

Description of the treatment method

The course of energotropic therapy included drugs such as L-carnitine (20-30 mg/kg/day), coenzyme Q10 (daily dose 60-90 mg/day), succinic acid (200 mg/day), citric acid (50 mg/day). day), B1 (100 mg/day), B6 ​​(200 mg/day), B12 (200 mcg/day).

The selected combination of drugs provided an optimal effect on various parts of mitochondrial metabolism.

The duration of the course of energotropic therapy in our patients was two months, the interval between courses was also two months. A total of two courses of energy-tropic therapy were carried out, after which the effectiveness of its use was assessed.

The effectiveness of energotropic therapy was analyzed according to three groups of indicators - clinical, biochemical and cytochemical.

Assessment of the dynamics of motor development before and after a course of energotropic therapy was carried out in 39 patients with congenital myopathies (20 patients with congenital structural myopathy of the “central core” and 19 patients with congenital muscular dystrophy) and was carried out using motor scales:

Functional Classification Overall Progressive Childhood Muscular Dystrophy Profile scale According to Vignos, 1960 (FC to Vignos). Using this scale, patients were classified into 10 functional classes according to their ability to move.

Muscular Dystrophy Score According to Scott et al., 1982 (MDS to Scott). The maximum possible number of points on this scale is 40 points, and the minimum is 0 points.

To assess motor abilities and identify manifestations of myopathic techniques, our patients underwent the Gowers test. The patient, from a sitting position on the floor with legs extended, had to stand up with maximum speed. It is believed that the patient, when performing the Gowers test, uses myopathic techniques when getting up from the floor; Normally, the Gowers test is performed for up to 5 seconds.

Test with climbing stairs 8 standard steps (the time spent on performing the test is recorded).

Test of walking on a plane at a distance of 9 meters (the time spent on performing the test is recorded).

Analysis of the dynamics of the motor skills of patients in accordance with objective scales and tests showed a significant improvement in motor functions in 35% of patients with “central core” disease and in 63% of patients with congenital muscular dystrophies according to the FC to Vignos scale (Fig. 1, 3). Positive changes in motor development were statistically significant (p<0,05) и у пациентов с врожденными структурными миопатиями «центрального стержня», и у пациентов с врожденными мышечными дистрофиями.

In addition, 15 out of 20 patients with “central core” disease managed to improve their MDS to Scott score by 1-4 points, which was also statistically significant (p<0,05). (Фиг.2). Еще более очевидна положительная динамика в двигательном развитии у пациентов с врожденными мышечными дистрофиями (Фиг.4). Все 19 пациентов без исключения дали позитивные сдвиги на 2-12 баллов. Очевидна положительная динамика двигательных нарушений, что подтверждается статистически (р<0,05). Следует отметить, что данная группа заболеваний всегда прогрессирует (быстро или медленно) и добиться улучшения у данной категории пациентов чрезвычайно тяжело.

The dynamics of the Gowers test performance indicators were also positive - 13 patients out of 20 (65%) with the disease of the “central core” began to climb the stairs faster, although they did not reach the standard indicators. The trend was not statistically significant (p=0.103) in our sample. In a group of patients with congenital muscular dystrophy, the study of the Gowers test is not advisable, since most patients are not able to stand up independently.

There was also a decrease in the rate of ascent on 8 standard steps before and after treatment in specific patients with congenital structural myopathy of the “central rod”, which was statistically significant (p<0,05) (Фиг.5).

There was also a statistically significant (p<0,05) улучшение показателей ходьбы по плоскости на 9 метров у 18 пациентов из 20 (90%) до и после лечения с врожденной структурной миопатией «центрального стержня».

Thus, analysis of the dynamics of motor indicators demonstrates clinical improvement in 60% of patients with disease of the “central” rod and in all patients with congenital muscular dystrophies.

When studying biochemical parameters, it was not possible to detect a statistically significant improvement in patients with congenital structural myopathy of the “central core” in lactic and pyruvic acid. However, there is a tendency to decrease the concentration of lactic acid before exercise (p = 0.183) and 3 hours after exercise (p = 0.071). In patients with congenital muscular dystrophy, the authors were unable to detect a statistically significant improvement in lactic and pyruvic acid levels.

In our sample of patients with central core disease, it was not possible to obtain a statistically significant improvement in cytochemical enzymes, despite an obvious increase in their activity. However, there is a tendency towards normalization of the cytochemical enzyme GPDG (p<0,775), активность которого была снижена в большей степени, чем других цитохимических ферментов.

In patients with congenital muscular dystrophies, GDH activity was more often affected. In our sample, we were able to obtain statistically significant results on an increase in the activity of the GDH enzyme after treatment (p<0,05).

Clinical example No. 1

Patient B., 14 years old, was admitted to the department of psychoneurology and epileptology of the Moscow Research Institute of Pediatrics and Pediatric Surgery of the Russian Medical Technology in November 2005 for the first time with complaints of weakness, gait disturbance, kyphoscoliotic curvature of the thoracolumbar spine, and deformation of the chest.

Anamnesis vitae. A child from young, clinically healthy parents who are not in a consanguineous marriage. Heredity for neuromuscular diseases is clearly not burdened, however, the younger sister (after examination in our clinic) was diagnosed with structural “multi-core” myopathy. A child from the first pregnancy, which occurred with anemia and toxicosis. Delivery is at term, lasting about 6 hours. She was born with asphyxia, with a body weight of 3450 g, length 52 cm. Apgar score was 6/7 points. Applied to the breast for 3 days. Early motor development occurred with a slight delay: she began to hold her head at 4 months, sit at 8 months, and walk at 1 year 6 months. Teeth appeared at 6 months. Phrasal speech from 1.5 years.

Anamnesis morbi. The girl had a dislocation of the hip joints from birth; at early school age, scoliosis began to progress (now kyphoscoliosis of the third degree); at the same time, there is a deformation of the shape of the chest. The girl received courses of nonspecific restorative therapy, but the disease steadily progressed.

Objective examination data. Upon admission, the girl’s condition due to the underlying disease was of moderate severity. Weight 43 kg, height 154 cm (weight and height indicators correspond to age). There are no cerebral or meningeal symptoms. The circumference of the skull is 51.5 cm. The shape of the skull is normal, with percussion the sound is normal. There are no changes in the cranial nerves. Head in the midline; head turns and shoulder lifting are somewhat limited due to scoliosis. The girl has grade III kyphoscoliosis, chest deformity, congenital dislocation of the hip joints, and a duck-like gait disorder. Passive and active movements are limited in the hip joints and left ankle joint. There is a decrease in muscle strength in the arms up to 3 points and in the legs up to 2-3 points. Muscle tone is diffusely reduced. Tendon reflexes: reduced in the arms; on the legs - the knees are alive, the Achilles are alive. Abdominal reflexes are evoked. There is slight swaying in the Romberg position. Coordinator tests run smoothly. No sensory impairment was detected. The functions of the pelvic organs are not impaired. No trophic disorders were identified.

Data from laboratory and functional studies. Biochemical blood test - CK activity 95 U/l (within normal limits), LDH 330 U/l (within normal limits). The lactate/pyruvate ratio is increased to 40 (normal is 20).

The result of cytochemical analysis of lymphocytes: succinate dehydrogenase - 17.4 (18.5-19.5), alpha-glycerophosphate dehydrogenase ~ 14.3 (11-14), glutamate dehydrogenase - 5.1 (10-15), lactate dehydrogenase - 10.4 ( 10-17). Conclusion: Decreased activity of the GDH enzyme.

ECG: sinus rhythm, moderate arrhythmia, tachycardia predominates. Horizontal position of the EOS. Shortening the PQ interval.

ECHO-KG. There were no signs of heart defects. Mitral valve prolapse. Additional trabecula in the left ventricle.

ENMG: Signs of primary muscle damage.

Ultrasound of internal organs: Reactive changes in the pancreas.

Consultation with a cardiologist: Cardiomyopathy in a child with structural myopathy.

Consultation with an ophthalmologist: Myopic astigmatism.

Surgeon consultation: Congenital structural myopathy. Combined chest deformity. Shortening of the left lower limb by 3 cm. Kyphoscoliosis 4 degrees, progressive. Left-sided clubfoot. Varus deformity of the wrist joints (S>D).

The girl underwent an incisional biopsy of muscle tissue for diagnostic purposes.

Pathomorphological changes in skeletal muscles. The general structure of the musculoskeletal tissue has not been changed. No pathological changes in the connective tissue membranes were detected. The shape and size of the mions, the size and distribution of the muscle nuclei, and the nature of the striations correspond to the norm. There are no atrophied or necrotic muscle fibers. The types of mions are distributed mosaically, their quantitative ratio is normal. No pathological inclusions were found. In all mions, a sharp decrease in all studied variants of histochemical activity in the central part of the fiber is determined. In 10% of myons, SDH-positive and CO-positive RRF phenomenon is determined (the norm is up to 5%). RRF intensity - 2 points. Mitochondrial index - 1.5 (normal - up to 1.0). Subsarcolemmal accumulations of glycogen, lipids and calcium are detected. Conclusion: Disease of the “central core”. Morphological signs of mitochondrial deficiency.

Thus, the girl was given a clinical diagnosis: Congenital structural myopathy of the “central core”. The girl underwent 2 courses of energy-tropic therapy (each course lasted 2 months), with a 2-month break between them. Positive dynamics are noted in the form of an increase in muscle strength, tolerance to physical activity has increased, the girl has become more confident in walking and climbing stairs. Our observation demonstrates a moderate severity course of congenital structural myopathy of the “central core”, accompanied by severe disabling deformity of the thoracolumbar spine and chest.

Clinical example No. 2

Patient S., 3 years old, was admitted to the Department of Psychoneurology and Epileptology of the Moscow Research Institute of Pediatrics and Pediatric Surgery for the first time in April 2007 with complaints of muscle weakness, multiple contractures, and severe delayed motor development.

Anamnesis vitae. A child from young healthy parents who are not closely related. There is no hereditary history of neuromuscular diseases. There are no environmental or occupational hazards. A boy from the first pregnancy, which proceeded with the threat of termination and taking dexamethasone. Delivery at term, pathological (prolonged labor - more than 20 hours; the mother was diagnosed with a clinically narrow pelvis during labor, emergency caesarean section, cephalohematoma). He was born with a body weight of 3340 g, length 51 cm. Apgar score 7/8. Early motor development was delayed: he began to hold his head at 5 months, sits at 10 months, does not walk independently at 3 years, teeth at 9 months, speaks at 1.5 years. Psychospeech development corresponded to age.

Anamnesis morbi. After birth, the child was transferred to the neonatal pathology department and discharged home after 7 days. From birth, the symptom complex of a “flaccid” child was noted. Consulted by a neurologist at 2 weeks, hospitalized at the Morozov Children's Clinical Hospital, where ENMG was performed and anterior horn activity was detected. Consulted with a geneticist, diagnosed with spinal muscular dystrophy, Werdnig-Hoffmann type. An MRI of the brain was performed and revealed periventricular leukomalacia, cortical atrophy, delayed myelination, and hypoplasia of the corpus callosum. A diagnosis was made: Perinatal encephalopathy. Myelodysplasia? the threat of developing cerebral palsy. From the age of 10 months, the child is observed in the 18th children's hospital with the diagnosis: Perinatal damage to the central nervous system (brain and spinal cord), flaccid tetraparesis. Hip dysplasia with hip subluxation. Equinovarus position of the feet. There is a slight positive dynamics in the child’s development: he began to sit, move his arms and legs. The boy was sent for examination to the Moscow Research Institute of Pediatrics and Pediatric Surgery.

Objective research data: The child’s condition is severe due to the underlying disease. Weight is 10.5 kg, height is 84 cm. The weight and height indicators are below the 3rd centile and correspond to: the weight indicator - 1 year, and the height indicator - 2 years. There are no cerebral or meningeal symptoms. The circumference of the skull is 49.5 cm. The shape of the skull is dolichocephalic, the sound during percussion is normal. There are no changes from the CMN side. He cannot hold his head up, independent motor activity is reduced. The boy does not walk, does not crawl, and sits with support. Passive and active movements are limited: flexion contractures in the ankle, knee, hip (hip dysplasia), elbow and wrist joints (angle no more than 5-9°). Muscle strength is sharply reduced to 1-2 points. Muscle tone is sharply reduced. Tendon reflexes: not evoked. Abdominal reflexes are not evoked. Does not perform coordination tests (active movements are reduced). There are no hyperkinesis. Pathological reflexes (Babinsky, Rossolimo) are negative. The functions of the pelvic organs are not impaired.

Data from laboratory and functional studies: Biochemical blood test - CK activity was 1285 U/l (6.7 times higher than normal), increased LDH activity - 730 U/l (increased 1.6 times), lactate/pyruvate ratio within age norm.

ECG: Severe sinus arrhythmia, heart rate 118-143 beats/min, period of tachycardia (the child was crying). Vertical position of the EOS. ST-T changes.

ECHO-CG: signs of a partially open oval window. Dilatation of the right and left ventricles with decreased myocardial contractility.

ENMG: No data were obtained regarding the neuronal and neuritic nature of the lesion. Diffuse pronounced decrease in the amplitude of the EMG curve, a decrease in the amplitude of the M-response at the distal point, which indicates the primary muscle genesis of EMG changes.

MRI of the brain: midline structures are not displaced, expansion of the arachnoid spaces in the frontal and temporal regions, expansion of the interhemispheric fissure, hyperintense in T2 focal signal changes in the white matter of both hemispheres of the cerebrum, corresponding to periventricular leukomalacia, the ventricular system is not expanded, the corpus callosum is thinned throughout throughout, the differentiation of the medulla is not expressed, corresponding to delayed myelination.

DNA analysis: The coding sequence of the LAMA2 gene, mutations in which are responsible for hereditary muscular dystrophy, was studied using direct automatic sequencing. Patient S. had mutations c.5422C>T and c.7701 del T ins GTGTCCCTAGGTGTCCCTA in a compound heterozygous state. Diagnosis: merosin-negative congenital muscular dystrophy was confirmed by molecular genetic methods.

Consultation with a speech therapist: Motor alalia. Dysarthria.

Consultation with a cardiologist: Dilated cardiomyopathy in a patient with myopathy (dilation of the left and right ventricles, decreased myocardial contractility, ST-T changes).

The child underwent an incisional biopsy of muscle tissue for diagnostic purposes.

Pathomorphological changes in skeletal muscles. The general structure of the musculoskeletal tissue corresponds to the picture of muscular dystrophy. The perimysium and endomysium are expanded and contain areas of increased cellularity. Myons are characterized by the presence of multiple necrosis and/or atrophy. No signs of structural myopathies were found. The distribution and general activity of the studied enzymes, the histochemical characteristics of glycogen, lipids and calcium correspond to the picture of myodystrophy. There is no RRF. Ultrastructural-polymorphic foci of mion destruction. Conclusion: Congenital muscular dystrophy.

Thus, the boy was given a clinical diagnosis: Congenital muscular dystrophy, merosin-negative. The boy underwent 2 courses of energy-tropic therapy (each course lasted 2 months), with a 2-month break between them. Positive dynamics were noted: muscle strength increased, the boy began to confidently hold his head, sits independently, rolls over, the child’s mobility and activity increased. Our observation demonstrates a rather severe course of merosin-negative congenital muscular dystrophy.

A characteristic feature of the disease is metabolic disorders in skeletal muscle tissue. The muscles of a sick child lose their function partially or completely, that is, weakness appears in them and the range of movements decreases. The quality of life is significantly reduced. Source: Komantsev V.N., Skripchenko N.V., Sosina E.S., Klimkin A.V. POLYNEUROPATHY AND MYOPATHY OF CRITICAL CONDITIONS IN ADULTS AND CHILDREN: DIAGNOSIS, CLINICAL MANIFESTATIONS, PROGNOSIS, TREATMENT // Modern problems of science and education. – 2012. – No. 5

This pathology usually has a hereditary form and can be diagnosed in children of any age.. It is not life-threatening, except in cases where atrophy of the heart muscle and respiratory muscles occurs. Source:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2796972/
Chris M. Jay, Nick Levonyak, Gregory Nemunaitis, Phillip B. Maples and John Nemunaitis
Hereditary Inclusion Body Myopathy (HIBM2) Gene Regul Syst Bio. 2009; 3: 181–190.

The disease has a number of complications:

• development of respiratory failure;
• limited mobility;
• paralysis;
• congestive pneumonia;
• depressive, suicidal mood of the patient;
• increased risk of death.

Is it possible to prevent the disease?

If there have already been similar cases in the family, then you need to consult a doctor who will develop a plan of preventive measures.

Causes of myopathy in children:

• hormonal imbalances;
• heredity;
• genetic defects (deficiency of an enzyme that ensures metabolic processes in muscles; defect of a cell that plays the most important role in the delivery of energy material to the muscles); Source:
  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5575512/
  Alessia Nasca, Chiara Scotton, Irina Zaharieva, Marcella Neri, Rita Selvatici, Olafur Thor Magnusson, Aniko Gal, David Weaver, Rachele Rossi, Annarita Armaroli, Marika Pane, Rahul Phadke, Anna Sarkozy, Francesco Muntoni, Imelda Hughes, Antonella Cecconi, György Hajnóczky, Alice Donati, Eugenio Mercuri, Massimo Zeviani
  Recessive mutations in MSTO1 cause mitochondrial dynamics impairment, leading to myopathy and ataxia Hum Mutat. 2017 Aug; 38(8): 970–977.
• systemic connective tissue lesions.

Symptoms and treatment of pathology in a child

Clinical signs of myopathy in children:

• change in gait;
• weakness that does not go away with rest;
• delayed motor development;
• flaccid, flabby muscles;
• atrophy (thinning) of muscles;
• curvature of the spine is a manifestation indicating weakness of the muscular corset.

Negative processes appear in children at an early and teenage age, but since myopathy develops slowly, it can go undetected for a long time. In addition, children are able to compensate for muscle deficiency by using other, healthy muscles more actively.

The most common changes are observed in the areas of the shoulders, legs, arms, pelvis, and chest. With this disease they are always bilateral and symmetrical.

As the disease progresses, movement disorders appear:

• it is difficult for a child to sit up from a lying position;
• movements are abnormal, “wrong”;
• when walking and/or running, fatigue quickly sets in;
• the child has difficulty maintaining balance and often falls;
• It is difficult for a child to climb stairs.

Appearance disturbances may also appear:

• protruding ribs;
• very thin, as if overtightened, waist;
• flattened chest;
• slouch;
• Irregular shape of legs - thick calves and thin thighs.

Diagnosis of myopathy

The disease is expressed:

• increasing symptoms;
• absence of seizures and neurological manifestations;
• selective localization;
• characteristic "duck" gait.

For an accurate diagnosis, first of all, an anamnesis is collected to find out whether there have been cases of this disease in the family. Then an examination is carried out by a neurologist, during which the doctor evaluates muscle tone, the spread of weakness, the presence of muscle thinning, the degree of body deformation, the severity of reflexes, gait, and asks the child to sit up from a lying position and stand up from a sitting position.

Laboratory diagnostics include:

• clinical blood test;
• muscle biopsy;
• checking thyroid hormone levels.

A genetic examination of the child and close relatives is also carried out. Source:
https://www.mda.org/disease/congenital-myopathies/diagnosis
The Muscular Dystrophy Association (MDA).

Types of disease

One of the classification features is cause of the disease. According to it, myopathy is distinguished:

• primary (appears independently at birth, in early childhood or adolescence);
• secondary (develops against the background of other diseases).

By location of weakness illness happens:

• proximal (muscles are weakened closer to the body);
• distal (muscles are weakened in the limbs further from the body);
• mixed.

There are also the following forms of the disease:

• Pseudohypertrophic (Duchenne-Griesinger). Appears at 3-6 years of age, rarely before one year. Mainly affects the muscles of the legs and pelvis. Associated lesions: weakness of the respiratory and cardiac muscles. There is a high probability of death even before adulthood.
• Landouzy-Dejerine. Begins at 10-15 years of age and affects the face. The facial muscles weaken, the lips protrude and thicken, and often the patient cannot close his eyelids. Then the muscles are involved in a descending manner down to the shoulder girdle.
• Erba-Rotta(youthful). The onset of the disease is 10-20 years, boys are mainly affected by this form. The processes take place from top to bottom or bottom to top, rarely throughout the entire body or in the face area.

Important! Congenital myopathy is one of the most dangerous forms in children, often resulting in death. Her treatment is limited to improving vitality and begins in the first months after birth. The main thing in therapy is the prevention of respiratory failure, the organization of tube feeding. As the child grows, orthopedic correction techniques are used, physiotherapy and social adaptation are of great importance.

Treatment methods

Important! The sooner you start treating a child, the greater his chances of a fairly high quality of life.

Treatment boils down to the following activities:

• injection of adenosine triphosphoric acid (ATP) in courses;
• iontophoresis;
• vitaminization;
• drugs to improve blood circulation;
• massage;
• use of orthopedic correction devices by the patient;
• the use of drugs for better neuromuscular conduction;
• hormone therapy;
• etc.

The hereditary form of the disease cannot be completely cured, but it is possible to specifically eliminate the main symptoms by:

• orthopedic correction;
• regular and breathing exercises.

Sometimes surgery is required. It is aimed at correcting scoliosis that occurs against the background of the underlying disease.

Promising methods for treating myopathy are the use of stem cells and gene therapy.

Advantages of contacting SM-Clinic

Our clinic employs some of the best pediatric neurologists in St. Petersburg, doctors of high categories with impressive experience. Your child will be able to undergo diagnostics using modern equipment, undergo laboratory tests without queues and in comfortable conditions. SM-Clinic specialists will develop an optimal treatment plan in a short time, taking into account the individual characteristics of the patient and the form of his disease.

Call us for additional questions and to schedule an appointment.

Sources:

1. Komantsev V.N., Skripchenko N.V., Sosina E.S., Klimkin A.V. Polyneuropathy and myopathy of critical conditions in adults and children: diagnosis, clinical manifestations, prognosis, treatment // Modern problems of science and education, 2012, No. 5.
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2796972/ Chris M. Jay, Nick Levonyak, Gregory Nemunaitis, Phillip B. Maples and John Nemunaitis Hereditary Inclusion Body Myopathy (HIBM2) Gene Regul Syst Bio. 2009; 3: 181–190.
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5575512/ Alessia Nasca, Chiara Scotton, Irina Zaharieva, Marcella Neri, Rita Selvatici, Olafur Thor Magnusson, Aniko Gal, David Weaver, Rachele Rossi, Annarita Armaroli , Marika Pane, Rahul Phadke, Anna Sarkozy, Francesco Muntoni, Imelda Hughes, Antonella Cecconi, György Hajnóczky, Alice Donati, Eugenio Mercuri, Massimo Zeviani
Recessive mutations in MSTO1 cause mitochondrial dynamics impairment, leading to myopathy and ataxia Hum Mutat. 2017 Aug; 38(8): 970–977.
4. https://www.mda.org/disease/congenital-myopathies/diagnosis The Muscular Dystrophy Association (MDA).

Pitsukha Svetlana Anatolevna
Clinic

The information in this article is provided for reference purposes and does not replace advice from a qualified professional. Don't self-medicate! At the first signs of illness, you should consult a doctor.

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Name of service (price list is not complete)	Price
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Congenital myopathies are a broad concept of nervous muscle disorders, a group of rare primary muscle defects that are inherited and cause hypotension at birth or during the neonatal period. Diseases belonging to the group of congenital myopathies have a complex clinical picture and similar symptoms, which significantly complicates their diagnosis and treatment.

It manifests itself as diffuse muscle weakness and decreased muscle tone, the severity of which directly depends on the type of myopathy and its level of complexity. In severe cases, it can lead to death from respiratory failure.

Congenital myopathy is a genetically determined disease. Different types of myopathy can be located at different chromosomal loci, and therefore can be inherited recessively, dominantly, or together with the X chromosome. Genetic pathology disrupts the synthesis of protein, which is part of muscle tissue, which leads to disruption of the structure of muscle fibers. As a result, the muscles lose the ability to contract normally, and muscle weakness is observed.

Congenital myopathy usually manifests itself in early childhood (very rarely manifests itself in adults) and retains its symptoms throughout the patient’s life. Most often, this disease progresses poorly or does not progress at all.

The pathogenesis of myopathy is not fully understood and the causes of its appearance are not clear. There is a hypothesis of a “membrane defect” in muscle cells and cytoplasmic organelles, which many neurologists call the cause of the onset of the disease.

Classification of congenital myopathy

Muscle biopsy provides certain biochemical and morphological data, on the basis of which all diseases of congenital myopathy can be divided into two large groups.

Congenital muscular dystrophies

The first group is congenital muscular dystrophy (impaired function and structure of muscle fibers as a result of a failure in the synthesis of proteins that make up their composition). There is no clear classification of congenital muscular dystrophies, but based on the hypotheses of the pathogenesis of this group of diseases, two groups can be distinguished:

• merosin-negative diseases, which are characterized by a deficiency or absence of the mezzanine protein, which is part of striated muscles;
• congenital structural myopathies and merosin-positive, in which the mezzanine concentration is normal.

The merosin-negative group of diseases is divided into several types:

• Fukuyama congenital muscular dystrophies;
• muscular-eye-brain syndrome;
• Walker-Warburg syndrome.

The clinical picture of diseases of the merosin-negative group is very similar to the symptoms of classical congenital myopathies, but a distinctive feature is the involvement of various brain structures in the general symptoms, which leads to further mental retardation and developmental delay. Diseases of the merosin-positive group much less often involve damage to the central nervous system (approximately 10% of patients have brain damage) and usually do not entail inhibition of intelligence. The clinical picture is characterized by spinal deformation and disruption of facial features.

Congenital structural myopathies

The second group is congenital structural myopathies (violations of the integrity of the cytoskeleton of muscle fibers and the occurrence of pathology in muscle biopsy). This group of diseases is characterized by a violation of the synthesis of proteins responsible for growth and other functions of muscle formation in the early development of the embryo.

Congenital structural myopathies include:

• central core disease;
• nemaline myopathy;
• centronuclear myopathy;
• megaconial myopathy;
• myopathy with disproportion of muscle fiber types;
• myopathy with multiple central cores;
• myotubular myopathy;
• myopathy with crystalline inclusions.

The clinical pictures of each of the diseases in this group are similar to each other and are characterized by muscle hypotonia and hypertrophy, decreased reflectivity in the tendons and increased concentrations of creatine phosphokinase in the blood. Slow progression is observed.

Symptoms of congenital myopathy

Congenital myopathy most often debuts in the first months of a child’s life. These diseases are characterized by the presence of the “flaccid baby” syndrome: a noticeable decrease in muscle tone, muscle weakness, poor muscle development and weakness during the sucking process. As the child develops, muscle weakness is more noticeable - lack of strength to stand on his feet or simply lift his body, difficulties may arise when walking or sitting, and there is a noticeable lag in physical development compared to other children of the same age.

Muscle weakness can be severe or mild. Most often, symptoms persist for the entire period of the patient’s life and practically do not progress or develop weakly. In some cases, it is possible to observe the inability to move independently, so the patient is forced to use a wheelchair, but the self-care skills acquired by him are not lost.

Congenital myopathies provoke not only weakness of the muscles of the limbs and back, but also the muscles of the respiratory muscles weaken, which is especially dangerous for infants. If muscle weakness of the respiratory tract is expressed to a small extent, then the development of respiratory failure is observed. This, in turn, provokes various respiratory diseases (bronchitis, all kinds of pneumonia). Sometimes respiratory failure leads to death in infancy. There are cases when muscle weakness decreases with age or, on the contrary, progresses.

In some cases, congenital myopathy also manifests itself in the form of dysmorphic facial features (elongated skull shape, high palate) or pathologies of skeletal development (scoliosis, clubfoot, congenital hip dislocation, kyphosis).

Characteristics of certain types of congenital myopathy

Central core disease

It is inherited in an autosomal dominant manner with incomplete penetrance (but sporadic cases of heredity also occur). This form of congenital myopathy is characterized by pathology of the proximal muscles of the limbs, but patients are able to acquire some motor skills. In infancy, delayed motor development and hypotonia are observed, but this disease can only be diagnosed at a later age with skeletal changes and severe muscle weakness. In this case, skeletal pathologies are observed: foot deformation, kyphoscoliosis, hip dislocation, shoemaker's chest.

Most often, patients have a fragile figure and short stature. When diagnosing the disease, a muscle biopsy is performed, which shows the presence of multiple or single discontinuous zones that are devoid of oxidative enzymes in some muscle fibers. Other laboratory tests may show normal results. Patients with central core disease are prone to developing malignant hyperthermia.

Nemaline myopathy

The second name for this disease is congenital non-progressive filamentous myopathy. Heredity is mainly transmitted in an autosomal dominant manner, but recessive and sporadic ones are also found. Possible death due to respiratory failure in early infancy. Severe skeletal pathologies are observed. The development of the disease may occur to varying degrees, or may not progress at all. In some cases, patients are forced to move using a sitting gurney, in others they suffer from respiratory failure. When diagnosing, a histological examination is carried out, which reveals unusual or rod-like, non-crimson bodies in the muscles. EMG usually confirms the diagnosis of myopathy.

Myotubular myopathy

This type of congenital myopathy is inherited in an autosomal recessive manner. Myotubular myopathy is characterized by the presence of centrally located nuclei in most muscle fibers. This resembles the appearance of the muscle on the myotubular fetal development. As a result, the disease got its name.

Diagnosis of congenital myopathy

Diagnosis of congenital myopathies is a complex process, since the doctor needs to differentiate and determine the specific type of myopathy in order to prescribe adequate treatment and make the correct diagnosis. A neuropathologist identifies neurological symptoms, conducts electrophysiological and biochemical studies to establish heterozygous carriage of the myopathic gene. Electromyographic examination using cutaneous electrodes often shows a decrease in the voltage of the EMG curve. When performing a biochemical blood test, an increased concentration of aldolase and creatine kinase is observed in the serum.

Treatment of congenital myopathy

Treatment of congenital myopathies is ineffective. There is no clear treatment at the moment. Scientists are still arguing about whether congenital myopathy can be treated. Medical institutes in different countries are conducting research at the gene level using stem cells. There is symptomatic treatment, which consists of influencing metabolic processes in the patient’s body, in particular, protein synthesis, and an attempt to normalize the functions of the autonomic nervous system. Most often, drug treatment includes taking anabolic hormones (Nerobol, Ceraxon, Retabolil, Somazin), ATP. Vitamin therapy is mandatory. Anticholinesterase drugs are also prescribed.

A mandatory part of the treatment process for congenital myopathies is physical therapy. This could be exercise in water or a set of exercises. Exercise therapy is supervised by a trainer or neurologist. In some cases, orthopedic correction is effective (for example, wearing orthopedic shoes, corsets or the use of orthopedic mattresses, pillows, chairs).

The condition and clinical picture of the disease is monitored by a neurologist, therapist, pediatrician, cardiologist and orthopedist-traumatologist.

These rare diseases differ from muscular dystrophies by the presence of specific histobiochemical and structural defects in muscle tissue. The disease is characterized by a non-progressive course, which, however, is not the rule. In typical cases, infants experience hypotonia and delayed motor development. Cobbler's chest, kyphoscoliosis, malposition of the head of the pelvic bone and concave foot (pes cavus) are often observed. Timely diagnosis is very important as long-term prognosis and treatment differ from those for muscular dystrophies.

There are four main forms of congenital myopathy: central-stem, nemaline (core) myopathy, myotubular (centronuclear) myopathy and congenital fibrous disproportion.

Central stem disease. This is the first described congenital myopathy, identified by Shy and Magee in 1956. The disease is inherited in an autosomal dominant manner, but sporadic cases occur. In infancy, hypotension and delayed motor development are characteristic, but the disease can attract attention only in adulthood, when muscle weakness or certain skeletal changes appear. Patients are small in stature with a fragile figure; Skeletal abnormalities are characterized by congenital hip dislocation, scoliosis, pes cavus, and cobbler's chest. Weakness of the muscles of the face and limbs (especially the limbs) is not very pronounced. When examining a muscle biopsy, muscle fibers are found with multiple or single discontinuous (discrete) zones (central masses of necrotic tissue) devoid of oxidative enzymes. Other laboratory tests are less diagnostically informative, since serum CK activity and EMG data may be normal. Patients with this pathology are predisposed to the development of malignant hyperthermia (see Chapter 8).

Nemaline myopathy. Nemaline myopathy, also called congenital nonprogressive filamentous myopathy, was described by Shy et al. in 1963. It is usually inherited in an autosomal dominant manner, but inheritance can also be recessive or sporadic. Hypotension often occurs in infancy, and death may occur due to respiratory failure. Skeletal abnormalities can be very pronounced. This is a sharply elongated face; high palate, poorly developed muscles, kyphoscoliosis, “cobbler's chest”, muscle weakness can spread to the face, soft palate, and limbs. The prognosis of the disease is very variable: sometimes the disease does not progress, and if it does progress, it forces patients to use a sitting gurney or leads to respiratory failure. Histological examination reveals bundles of thread-like or rod-like nemaline bodies in the muscles, which is where the name of this disease comes from. Rods are derivatives of the Z-fascicular substance and are typically found in type I muscle fibers. and in the affected muscles, as a rule, muscle fibers of this particular type predominate. Serum CK activity may be normal or slightly elevated. EMG usually reveals myopathy.

Myotubular myopathy. This disease was described by Spiro. Shy and Gonatas in 1963

Histological changes in myotubular myopathy resemble the embryonic stage of development of muscle “tubes” during the formation of muscle fibers. Some authors prefer to call the disease centronuclear myopathy, believing that the muscle fibers are not embryonic in nature. The disease usually occurs sporadically, but inheritance may be autosomal dominant, recessive, or X-linked recessive. Hypotonia and muscle weakness occur in infancy, which can cause death. When presenting at an older age, the disease may resemble nemaline myopathy. In this case, patients have a narrow, elongated face, concave foot, and scoliosis. Overall muscle mass is usually reduced. and the degree of proximal and distal muscle weakness varies. This differs from other congenital myopathies by the presence of external ophthalmoplegia. The course of the disease can be either progressive or non-progressive. Serum CK activity is normal or slightly increased. The EMG is pathologically altered: the potentials of the motor units are reduced and over-equipped. Muscle biopsies reveal muscle fibers with rows of centrally located nuclei, often surrounded by a clear perinuclear zone. Type I muscle fibers are more affected and may undergo atrophy.

Congenital imbalance in the ratio of muscle fiber types. Clinical manifestations of this disease include hypotonia, muscle weakness, delayed physical development, and skeletal abnormalities, as with other congenital myopathies.

The diagnosis is based on the results of a muscle biopsy: the biopsy specimen shows an increase in the number of small type I muscle fibers and normal or hypertrophied type II muscle fibers. The pathogenesis of the disease is poorly understood. The prognosis is usually favorable; for many patients, their condition improves with age, although motor impairments of varying degrees still remain. In some patients, muscle weakness progresses.

Diseases caused by impaired energy metabolism in muscles

Skeletal muscle typically utilizes two main sources of energy: fatty acids and glucose. Consequently, impaired glucose or fat utilization may be accompanied by clear clinical manifestations in the muscular system. The most severe manifestation of this pathology is acute muscle pain syndrome, which can lead to severe rhabdomyolysis and myoglobinuria. Also worth mentioning is progressive muscle weakness simulating muscular dystrophy. There is no explanation for the existence of these two different clinical syndromes.

Glycogenosis (glycogen storage disease) and glycolytic defects. There are four types of disorders of glycogen metabolism (types II, III, IV and V) and four types of disorders of glycolysis (types VII, IX, X and XI), which are manifested by significant disorders of the skeletal muscles (see also Chapter 313).

Acid maltase deficiency (type II glycogenosis). Acid maltase is a lysosomal enzyme from the group of acid hydrolases, which has -1,4 and -1,6 glucosidase activity: it breaks down glycogen into glucose. At the same time, the role of this enzyme in carbohydrate metabolism is not clearly defined. There are three clinical forms of acid maltase deficiency, each of which is inherited in an autosomal recessive manner. The biochemical basis for the various clinical manifestations of this enzyme deficiency is unclear.

In infancy, acid maltase deficiency manifests itself as general glycogenosis. At birth, no pathology is found, but soon severe muscle weakness, cardiomegaly, hepatomegaly and a noticeable increase in the size of the tongue are detected. The accumulation of glycogen in the motor neurons of the spinal cord, as well as in the brain stem, aggravates muscle weakness. Such infants usually die within the first year of life.

In children and adults, this disease manifests itself as muscular dystrophy. Childhood forms of the disease are characterized by slow development of the child, weakness of the proximal muscles of the extremities, and an increase in the size of the calf muscles. The disease may progress with the development of respiratory failure; death usually occurs at the end of the 2nd decade of life. Cardiac involvement may occur, but hepatomegaly and macroglossia are rare.

The disease in adults begins in the 3rd-4th decades of life and can be mistakenly diagnosed as limb-girdle dystrophy or polymyositis. The initial manifestation of the disease is respiratory failure caused by weakness of the diaphragm. The liver, heart and tongue are usually not affected. The assumption of the diagnosis arises after examining a muscle biopsy, in which vacuoles containing glycogen and acid phosphatase are found. Electron microscopy shows that glycogen is both associated with membranes and freely located in tissues. The final diagnosis is made by biochemical examination of the affected muscle. The activity of acid maltase in urine is reduced. The level of serum activity of CK can exceed the norm by 10 times. With EMG, maltase deficiency can be differentiated from muscular dystrophy by high-frequency myotonic discharges accompanying short motor unit potentials against the background of fibrillations and positive spiky potentials.

Insufficiency of the enzyme that inhibits the branching of the glycogen molecule (type III glycogenosis). This rather mild childhood disease is manifested by hepatomegaly, growth retardation and hypoglycemia; mild muscle weakness is rarely observed. After puberty, these symptoms usually decrease in severity or disappear completely, so muscle weakness and some decrease in muscle mass may simply be due to a decrease in physical activity due to poor exercise tolerance. An assumption about a possible diagnosis arises when, after the patient performs a special exercise for the muscles of the forearm, the content of lactic acid in the blood does not increase. Serum CK activity is usually increased. EMG reveals changes characteristic of myopathy, as well as signs of increased irritability of membranes by myotonic impulses. In muscle biopsy, vacuoles with increased glycogen content are found. To confirm the diagnosis, a biochemical study of the muscle is required.

Glycogen branching enzyme deficiency (type IV glycogenosis). Deficiency of this enzyme is a very severe, fatal pathology of infancy, in which disorders of the skeletal muscles fade into the background compared to the development of chronic liver failure. However, muscle hypotonia and muscle atrophy may suggest a primary muscle disease or spinal muscular atrophy.

Muscle phosphorylase deficiency (type V glycogenosis). Poor exercise tolerance is a characteristic symptom of muscle phosphorylase deficiency, first described in 1951 by McArdle. The disease is inherited in an autosomal recessive manner; men get sick more often than women. After puberty, patients experience painful muscle cramps and rapid muscle fatigue after intense physical activity - running, lifting weights. The literature describes variants of the disease that begin both in infancy and later. Many patients report the phenomenon of a “second wind” that occurs after a short rest or after slowing down the pace of physical activity, which allows them to maintain physical activity for many years. Physical fatigue in such patients leads to the development of rhabdomyolysis, myoglobinuria and renal failure. Persistent muscle weakness and progressive muscle atrophy are rare, so physical examination during periods between exacerbations of the disease usually does not reveal pathology. Other organs are not affected by this disease.

Serum CK activity is subject to significant fluctuations and may be elevated even during asymptomatic periods. A load test on the forearm muscles is not accompanied by an increase in lactic acid levels in the blood. EMG findings are normal unless performed immediately after an episode of rhabdomyolysis. Muscle biopsy reveals “vesicles” containing glycogen under the sarcolemma. The presence of muscle phosphorylase deficiency can be determined using histochemical staining of a histological specimen or by biochemical examination of muscle tissue. Patients can remain quite active throughout their lives, provided they abstain from certain physical overloads. Diet replacement therapy with glucose or fructose is usually not accompanied by a weakening of the symptoms of the disease.

Phosphofructokinase deficiency (type VII glycogenosis). This disease resembles muscle phosphorylase deficiency and is also inherited in an autosomal recessive manner; Among the sick, males predominate. The same as for phosphorylase deficiency, provoking moments and laboratory data. This type of enzyme deficiency is detected by histochemical staining of a muscle preparation for phosphofructokinase (FFrK). For a reliable diagnosis, a biochemical study of muscle enzymes is necessary. In some patients with deficiency of this enzyme, mild hemolysis, an increase in the number of reticulocytes in the peripheral blood, as well as an increase in the content of bilirubin in the blood are possible, since FFrK deficiency occurs not only in the muscles, but also in the red blood cells.

Syndromes associated with deficiency of a new glycolytic enzyme. Since 1981, deficiencies of three additional glycolytic enzymes have been identified: phosphoglycerate kinase (PGlK) (type IX), phosphoglycerate mutase (PGlM) (type X), and lactate dehydrogenase (LDH) (type XI). The clinical picture of all three types of enzyme deficiency is identical. In early childhood or adolescence, after physical overexertion, patients experience episodes of myoglobinuria and myalgia. It seems that all these enzyme defects are inherited in an autosomal recessive manner. Serum CK activity may be increased during exacerbations of diseases,

Rice. 357-1. Lipid metabolism.

Free fatty acids as an energy source are formed from triglycerides accumulated in the muscle and from circulating very low-density lipoproteins, which are broken down by endothelial lipoprotein lipase (1) in the capillaries. Carnitine, an essential substrate for lipid metabolism, is produced in the liver and transported to muscle. In muscle, free fatty acids combine with coenzyme A (CoA-SH) under the influence of fatty acyl synthetase (2), found in the outer mitochondrial membrane, resulting in the formation of fatty acyl-coenzyme A (F-acyl-CoA). Transport across the inner mitochondrial membrane requires carnitine transfer by carnitine palmitine transferase I (CPT-1), bound to the outer surface of the inner mitochondrial membrane (3). Within the mitochondria, fatty acylcarnitine (F-acylcarnitine) is synthesized by CPT-P (4), which is associated with the inner surface of the inner mitochondrial membrane. In this case, fatty acyl coenzyme A undergoes -oxidation.

and between exacerbations. With insufficiency of FGLM and LDH, the increase in lactic acid levels in the blood after a load on the forearm muscles is usually lower than normal. With PGLK deficiency, the blood lactate level does not increase at all after exercise. In general, this form of enzyme deficiency in its clinical manifestations is very similar to the deficiency of muscle phosphorylase and phosphofructokinase. Histological examination of muscles in these forms of enzyme deficiency is usually uninformative; only a slight increase in glycogen content in the muscles is noted. For reliable diagnosis, a biochemical study of the muscle is necessary.

Lipid metabolism disorders. Lipids are an important energy substrate, especially during muscle rest and during prolonged but mild physical activity (Fig. 357-1).

Carnitine deficiency. There are myopathic and systemic (generalized) forms of carnitine deficiency.

Myopathic carnitine deficiency usually occurs with generalized muscle weakness, which usually begins in childhood. The clinical manifestations of this disease are partly reminiscent of muscular dystrophy, and partly of polymyositis. Most cases are sporadic; It is believed that the disease can be inherited in an autosomal recessive manner. Sometimes cardiomyopathy occurs. Serum CK activity is slightly increased; EMG shows signs of myopathy. In the muscle biopsy, a pronounced accumulation of lipids is detected. The carnitine content in the blood serum is normal. It is believed that in this disease the transport of carnitine into the muscles is impaired, which is why its content in the muscles is so low. Some patients respond positively to oral carnitine replacement therapy, in any case it should be tried in all cases. Other patients responded favorably to prednisolone treatment for unknown reasons. In some patients, replacing medium-chain triglycerides with long-chain triglycerides in their diet has had a therapeutic effect. Some patients respond well to treatment with riboflavin.

Systemic carnitine deficiency is an autosomal recessive disease of infancy and early childhood. It is characterized by progressive muscle weakness and episodes of hepatic encephalopathy with nausea, vomiting, blackout, coma and early death. The low content of carnitine in the blood serum distinguishes this form from myopathic carnitine deficiency. There is no known reason that could cause or explain low carnitine levels in the blood. Some patients show reduced synthesis of carnitine, while others have increased excretion in the urine. Serum CK activity may be slightly increased. In the muscle biopsy, accumulation of lipids is found. In some cases, their accumulation is also noted in the liver, heart and kidneys. In some patients, but not all, oral carnitine or corticosteroids have been effective.

Carnitine palmityl transferase deficiency. This enzyme deficiency is manifested by recurring myoglobinuria. It is not known exactly whether the decrease in the activity of which carnitine palmitine transferase (CPT) occurs in this case: CPT-I or CPT-II. This enzyme deficiency appears to be the result of dysregulation of the properties of the pathological enzyme. Great physical activity (playing football, long hike) can provoke rhabdomyolysis; however, sometimes the precipitating factor cannot be identified. The first signs of the disease often appear in childhood. Unlike muscle lesions in glycolytic disorders, when muscle cramps appear after short-term but intense physical activity, which forces the patient to refuse to continue physical activity and thereby protect himself, with CBT deficiency muscle pain does not occur until all the energy resources of the muscle are used up and its destruction will not begin. During rhabdomyolysis, severe muscle weakness occurs, so that some patients may need artificial ventilation. In contrast to carnitine deficiency, when CBT is insufficient between attacks of the disease, muscle strength is preserved, and muscle biopsy does not reveal lipid accumulation in it. The diagnosis requires direct examination of the CPT content in the muscle. Treatment involves increasing dietary carbohydrate intake before exercise or replacing medium-chain triglycerides with long-chain triglycerides in the patient's diet. However, all these treatment methods are not completely satisfactory.

Myoadenylate deaminase deficiency. The enzyme adenylate deaminase converts 5-adenosine monophosphate (5-AMP) to inosine monophosphate (IMP) to release ammonia, which may play a role in regulating muscle adenosine triphosphate (ATP). In 1978, it was possible to identify a group of patients with muscle pain and exercise intolerance who had a deficiency of the myoadenylate deaminase isoenzyme. Deficiency of this enzyme is quite common and occurs in approximately 1% of the population, which can be determined by special staining of muscle histological preparations or by biochemical examination of muscle tissue. When examining a load test on the muscles of the forearm, a decrease in ammonia formation is detected. Since the original description of this disease, clearer clinical manifestations have not been identified. Often, patients with other neuromuscular pathologies (damages to the cells of the anterior horns of the spinal cord, muscular dystrophy, myasthenia gravis) are also found to be deficient in this enzyme. The clinical significance of this disorder has not been clearly established.

Mitochondrial myopathies. A heterogeneous group of diseases characterized by mitochondrial pathology owes its name to a special type of trichrome-stained histological preparation of biopsied muscle. Kearns-Sayre syndrome is a sporadic disease that begins in childhood and is characterized by progressive external ophthalmoplegia, intracardiac conduction disorders, which often leads to complete transverse block. Retinal degeneration, short stature of patients, and gonadal defects are also noted.

An inherited disorder with progressive external ophthalmoplegia and proximal muscle weakness may be difficult to distinguish from Kearns-Sayre syndrome. Recently, another syndrome has been identified, designated by the acronym MERRF 1, in which the myoclonic form of epilepsy is combined with “rough red fibers” found in histological muscle preparations. This disease occurs between the first and fifth decades of life and is characterized by generalized seizures, myoclonus, dementia, hearing loss and ataxia.

The third disease from this group is MELAS 2 syndrome (1 MERRF - myotonic epilepsy, ragged-red fibers (ed. note). 2 MELAS - myopathy encephalopathy, lactic acidosis, stroke-like episodes (ed. note)., which is a slowly progressive disease characterized by mitochondrial myopathy, encephalopathy, lactic acidosis, stroke-like episodes with the development of transient hemiparesis, hemianopsia or cortical blindness, and focal or generalized seizures. The cause of mitochondrial myopathies is unknown, but there is evidence that it is familial. In some cases, the disease may be transmitted by mitochondrial rather than chromosomal DNA.

Myopathy is a heterogeneous group of diseases based on primary damage to muscle tissue.

Another term for myopathy is myodystrophy, which is more often used to refer to hereditary myopathies.

Primary damage to muscle cells can occur under the influence of various etiological factors (heredity, metabolic disorders, bacteria). The accepted classification of myopathies is based on this fact.

Classification

The leading etiological factor of many types of myopathies is heredity.

The following types of myopathies are distinguished:

1. Progressive muscular dystrophy.

• Becker's myopathy.
• Landouzy-Dejerine myopathy.
• Emery-Dreyfus myopathy.
• Limb-girdle form of progressive muscular dystrophy.
• Ophthalmopharyngeal form.
• Distal myopathies (Mioshi myopathy, Welander myopathy, etc.)

1. Congenital muscular dystrophies and structural myopathies.
2. Metabolic myopathies (mitochondrial myopathies, endocrine).
3. Inflammatory myopathies.

The classification indicates the most common muscular dystrophies, but this is not a complete list.

Symptoms

The main symptom of all myopathies is muscle weakness. The proximal parts of the extremities (shoulder girdle, shoulders, hips, pelvic girdle) are involved more often than other parts of the body.

Each type of muscular dystrophy affects certain muscle groups, which is important when making a diagnosis. Muscles are affected symmetrically. If weakness manifests itself in the muscles of the pelvic girdle and legs, then such a person, in order to get up from the floor, uses a staged rise: rests his hands on the floor, then on his knees, then rises with the help of support on furniture (bed, sofa). It seems that he is “climbing on his own.” Difficulty climbing stairs or uphill. It becomes necessary to use your hands when lifting. With the development of weakness in the hands, difficulties arise when combing hair. When the muscles supporting the spine are weak, there is an increased bending of the lower back forward. Damage to the scapular muscles leads to the lag of the lower edge of the shoulder blades from the back (“pterygoid” shoulder blades). Facial muscles suffer less often than others and only in some myopathies. A person experiences drooping of the upper eyelids (ptosis), drooping upper lip, articulatory speech disorders, and swallowing disorders. With weakness in the hands, a person has difficulty performing highly differentiated work (writing, playing musical instruments, turning, etc.). Weakness of the feet is manifested by the formation of a hollow foot and a flopping gait.

Over time, muscle tissue breaks down and atrophied muscles appear. Against the background of muscle atrophy, connective tissue grows, which creates a false impression of trained, pumped up muscles - muscle pseudohypertrophy. Contractures form in the joints, tightening of the muscle-tendon fiber, which leads to limited mobility in the joints and pain.

For most myopathies, the clinical picture has the same signs. Let us dwell on the most common myopathies, which differ in the age of onset of the disease, the rate of progression of the process, and the cause of occurrence.

Progressive muscular dystrophies

These are hereditary diseases, which are based on the death of muscle fiber with gradual replacement by adipose tissue. This group is characterized by rapid progression of the process, which leads to human disability.

1. Duchenne and Becker myopathies.

Myodystrophies have a similar clinical picture . The diseases are recessive and are transmitted on the X chromosome, so only boys are affected. The pathology is based on a structural disorder (Becker myopathy) or complete absence (Duchenne myopathy) of a special protein - dystrophin, which is involved in the work of neurons, skeletal muscle fibers, and the heart. Pathological changes in the structural protein lead to necrosis of muscle cells - atrophy. Duchenne myopathy occurs several times more often than Becker myopathy. The onset of Duchenne muscular dystrophy occurs at an early age (age from 3 to 7 years). The first symptoms are non-specific, and at first parents often attribute them to character traits: inactivity compared to peers, passivity in games. Pseudohypertrophied muscles do not cause suspicion. Over time, the clinical picture worsens: the child stops getting up from the floor without support, and a duck's gait appears due to weakness of the pelvic girdle muscles. Walking on your toes appears because the Achilles tendons change and prevent you from standing on your heels. Intelligence is reduced.

The clinical course progresses rapidly and by the age of 9-15 years the child loses the ability to move independently and disability occurs. Upon examination, contractures (tightening) in the ankle joints are revealed. The muscles of the thighs, pelvic girdle, back, and upper arms atrophy. Often in children, atrophy is not noticeable due to the development of subcutaneous fatty tissue. Osteoporosis, dilated cardiomyopathy and respiratory failure are added. The child wakes up with a feeling of fear, suffocation, lack of air against the background of a decrease in the vital capacity of the lungs and the development of respiratory failure.

Death occurs at the age of 20-30 from respiratory or heart failure.

Becker myopathy is more mild. The clinical picture is generally similar to that of Duchenne myopathy, but the onset of the disease occurs at a later age (11-21 years). A person loses the ability to move independently at a later age (after 20 years). Cardiac involvement is less common compared to Duchenne muscular dystrophy. Intelligence preserved.

1. Landouzy-Dejerine myopathy .

The disease affects the muscles of the shoulder girdle and shoulders, as well as the facial muscles. The debut of myodystrophy occurs in the second decade of a person’s life. Initially, weakness and atrophy appears in the muscles of the shoulder girdle, which is manifested by the distance of the shoulder blades from the back (“wing-shaped” shoulder blades), the shoulder joints are turned inward, the chest is flattened in anteroposterior size. Gradually, the facial muscles are involved in the process: speech becomes unintelligible, the upper lip drops (“tapir lips”), the person’s smile becomes horizontal without raising the corners of the lips (Gioconda’s smile). In some people, atrophy affects the muscles of the legs, especially the legs. A characteristic symptom is asymmetrical muscle atrophy. Pseudohypertrophy does not always occur. Joint contractures are less pronounced compared to Duchenne myopathy.

Muscle weakness and atrophy are combined with dilated cardiomyopathy, retinal detachment, and hearing loss. In some patients, motor activity is maintained until the end of life and does not lead to severe disability, but another part of the patients is confined to a wheelchair in the third decade of life.

1. Emery-Dreyfus myopathy.

Progresses slowly. The first symptoms appear in children aged 5-15 years. The muscles of the arms and shoulder girdle are affected, and contractures gradually form in the elbow joints and hands. At the same time, the muscles of the feet atrophy, so the child “slaps” his feet when walking. By a certain age, the process stabilizes. Climbing stairs remains possible without the use of improvised means. Pseudopertrophy is not typical. If on the part of the skeletal muscles the changes are not so pronounced as to chain the child to a wheelchair, then on the part of the heart they are life-threatening. Dilated or hypertrophic cardiomyopathy develops, which disrupts the functioning of the heart, leading to arrhythmias, blockages, and in severe cases, death. For such patients, an artificial pacemaker is installed.

1. Erb-Roth limb-girdle myodystrophy.

It occurs equally often in men and women. Features of the clinical picture include development in 20-30 years, disability occurs 15 or more years from the moment the first symptoms appear. The muscles of the shoulder girdle and pelvic girdle are affected equally. Upon examination, the person’s duck-like gait, standing “on his own,” and “wing-shaped” shoulder blades attract attention. Pseudohypertrophy is not formed, the facial muscles remain intact. Changes in the heart are not observed.

1. Ophthalmopharyngeal myodystrophy.

It is manifested by drooping of the upper eyelids (ptosis), choking when swallowing (dysphagia) and the appearance of a nasal tone of voice (dysphonia), followed by weakness in the muscles of the arms, shoulders, legs and pelvic girdle.

1. Distal myodystrophies.

They are divided into several types depending on the onset of the disease: with onset in infancy, with onset in childhood, with late onset (Welander type), Mioshi type, with accumulation of desmin inclusions.

Distal myodystrophies are manifested primarily by damage to the muscles of the feet and hands. Noteworthy is the appearance of slapping feet when walking. Over time, a hollow foot (increase in the arch of the foot) or pseudohypertrophy of the leg muscles, scoliosis may form. A person is worried about weakness in the extensor muscles of the hands, which creates difficulties in finely differentiated work with the hands. Different subtypes of distal myopathies progress at different rates. In some subtypes, muscle damage extends higher (hips, legs, forearms, shoulders, neck).

Rare forms of progressive muscular dystrophy include scapuloperoneal myodystrophy, pelvic-femoral Leiden-Moebius myodystrophy, Mabry muscular dystrophy, etc.

Congenital muscular dystrophies

Sooner or later, most myopathies lead to disability of the patient.

This term refers to myopathies that arose in a child immediately after birth or in the first months of life. Diagnosis of the disease is based on the following criteria:

• Muscle hypotension (decreased muscle tone) of a child from the first days of life;
• Biopsy confirmation of myopathy;
• Other diseases with a similar clinical picture were excluded.

From the first days of life, the child experiences generalized weakness of all muscles. Weakness in the diaphragmatic muscles leads to impaired ventilation of the lungs and infection (the main cause of death), weakness in the neck muscles leads to the inability to hold the head, weakness in the arms and legs - “frog pose”. The child is significantly behind in motor development, but his intelligence is preserved. Another distinctive feature is contractures in many joints (elbows, ankles, knees). In some children, changes in the central nervous system (anomalies, demyelination, etc.) are simultaneously detected.

Congenital myodystrophies include Fukuyama myopathy, congenital myodystrophy with leukodystrophy and cerebroocular myodystrophy.

The causes and mechanisms of development are not fully known.

Inflammatory myopathies

According to the causative factor they are divided into the following groups:

Inflammatory myopathies occur with pain at rest and during muscle movement. Upon examination, muscle soreness and symptoms of intoxication are revealed.

Metabolic myopathies

These diseases are hereditary or acquired in nature, based on metabolic disorders in muscle cells.

Along with muscle weakness, other symptoms of metabolic disorders and endocrine changes appear.

Diagnostics

Electroneuromyography will help diagnose muscle weakness.

Diagnostic measures include several areas:

1. Collecting a family history (presence of the disease in relatives).
2. Neurological examination.
3. Laboratory methods.

• Biochemical blood test for CPK (creatine phosphokinase - an enzyme that appears during muscle breakdown).
• Blood test for sugar, hormones.

1. Instrumental research.

• ENMG().
• Muscle biopsy (one of the reliable diagnostic methods).
• ECG and ECHO-CG (detection of changes in the heart).
• Assessment of vital capacity (detection of respiratory disorders)
• DNA diagnostics (genetic examination).

Treatment

The main goal in the treatment of patients with hereditary myopathies is to delay the onset of immobility with the rapid formation of contractures and respiratory disorders.

1. Non-drug treatment.

Passive and active movements in the joints several times a day. Breathing exercises. The intensity of the load depends on the stage of the disease and is carried out in a gentle and protective manner so as not to provoke a deterioration of the condition.

• Gentle massage.
• Orthopedic correction is aimed at preventing the development of pathological conditions in the arms and legs, combating contractures with the help of special orthopedic splints and patient positions.
• A diet high in protein, vitamins and microelements.

1. Drug treatment.

The possibilities of medical assistance are significantly limited, since there is no specific treatment. Symptomatic treatment is aimed at maintaining the activity of healthy muscle tissue, reducing contractures and atrophies.

Treatment includes the following groups of drugs:

• B vitamins, vitamins A and E.
• Non-steroidal anabolics (potassium orotate, ATP).
• Cardiotrophic drugs (riboxin, carnitine chloride).
• Microcirculation correctors (pentoxifylline).
• Nootropics (piracetam).

1. Surgical treatment is also aimed at combating contractures when conservative methods are ineffective. The tendons or muscles are dissected (achillotomy, myotomy).

Treatment of other myopathies is carried out within the framework of the disease that caused them (treatment of influenza, toxoplasmosis, etc.).

First Medical Channel, neurologist G. N. Levitsky gives a lecture on the topic “Acquired and metabolic myopathies”:

Educational program in neurology, issue on the topic “Myopathies”: