Spinal amyotrophy. Spinal Amiotrophy of Verdnig-Hoffman: Causes, Signs Genetic Muscle Atrophy in Adults

What if you are diagnosed with motals? This is a rare disease earlier to the children for severe disability. But now programs for the rehabilitation of patients are developed. Scientists have made a huge breakthrough in therapy: a drug has been developed for the treatment of illness.

Disease prevalence, research history

SMA: What is this disease? Spinal Muscular Atrophy (Spinal Muscular Atrophy) is a rare disease called orphans. It is episodically found in the population and is genetic.

In the world, the diagnosis of spinal amyotrophy (SMA) receives one infant of 6000-10000. Such pathologies are little studied, it is difficult to diagnose and treatment. Including spinal amyotrophy. About 30% of children with orphan diseases do not live up to 5 years.

For the first time spinal amiotrophy (Spinal Atrophy) was described in the works of Verdiga at the end of the 19th century. He discovered pathological changes in muscles, peripheral nerves and in the spinal cord in children with motor disorders. In the descriptions of the Verdyign, it is noted that atrophy (atrophy) in the spinal cord is symmetrical and affects the front horns of the structure + front (motor) roots. Later, Gooffman distinguishes the disease in separate nosology.

Why does Spinal Amiotrophy appear (Spinal Atrophy)? Scientists say that this is the result of the Mutation of the SMN1 gene. The defect of this gene is every 40th inhabitant of the planet. Spinal Atrophy (Spinal Muscular Atrophy) can appear in the family from clinically healthy people. The probability of birth of a patient child in two carriers is made up 25%.

Spinal amyotrophy appears in childhood. It is accompanied by atrophy of the muscles of the lower extremities, the inability to walk, sit, keep his head. Sucking, swallowing, respiratory function is broken. Such defects give a strong developmental delay in children.

Causes and factors for the occurrence of disease

Why does spinal amyotrophy appear? What risk factors can be allocated? What is the main reason for the aless? It is genetic in nature and is transmitted to an autosomal recessive way. In this case, the defective gene should be at both parents. In this case, the child's spinal atrophy arises in 25% of cases.

How do genes affect the development of the disease? The spinal amyotrophy appears with a deficiency or with the absence of SMN protein. It provides the survival of motor neurons. His drawback is the main cause of muscle atrophy with SM. Brain cells die, and they are not a signal to the muscles.

In deletion of the long shoulder of the 5th chromosome, on which the SMN 1 gene is located, the protein is not produced. Spinal amyotrophy develops.

Corresponds a copy of the SMN2 gene. It is not functional. But in the absence of the main gene, SMN2 makes it possible to produce the desired protein, albeit in small quantities. The more copies of the SMN2 gene in the patient, the easier the spinal amyotrophia flows.

Risk factors:

1. Family history is burdened by stillbirth;
2. The disease was revealed in close relatives;
3. Married cases of infant mortality;
4. Spinal amyotrophy from the older child.

The likelihood of muscular atrophy in younger children is 1: 4.

How to recognize sch

Atrophy muscles in children during SMCULAR ATROPHY (Spinal Muscular Atrophy) can begin at different times. The hardest form of muscular atrophy in newborns appears in the first six months of life. Kid sluggish, bad sucks. In 3-4 months, the child does not turn into independently, does not make attempts to crawl. When spinal muscular atrophy, the baby's pose resembles a "frog".

There is a type of illness that appears after 7-18 months. Atrophy muscles leads to a regression in a child learned skills. The kid who crawled and began to get up, suddenly becomes a larger. Over time, he stops sitting smoothly. In the spinal cord atrophy (Spinal Atrophy), reflexes from the upper and lower extremities are disappeared.

Symptoms of muscle atrophy at Spinal Muscular Atrophy can occur closer to two years. Patients have already mastered standing and walking skills. At the same time, muscle atrophy attracts them to a wheelchair. Intellect, urination and defecation functions are saved. SMA after 2 years is the easiest type of disease.

How does muscle atrophy be determined independently? At Spinal Atrophy Muscles decrease in volume, become soft and flabby.

SPINAL MUSCULAR ATROPHY has the following signs:

1. Appears in infancy or childhood;
2. Accompanied by a walking violation, running, standing;
3. Tremor and fasciculation (twitching) are revealed;
4. The "rollback" of motor skills is determined;
5. In spinal atrophy, disruption of intelligence and vegetative functions do not reveal.

If the child has been found these signs, it must be advised by specialists. The diagnosis of SMA is exhibited based on DNA testing.

Description of spinal-muscular atrophy

SMN protein deficiency leads to the death of motor neurons of the front spinal cord. Following innervation violation, muscle atrophy begins. Spinal Atrophy begins with the muscles of the lower extremities. Muscular atrophy affects the muscles of the shin, hips and feet. The proximal muscle groups are affected faster.

Muscle atrophy takes place in young children. In the process of the disease (SPINAL ATROPHY) quickly turns on muscles responsible for sucking, breathing, swallowing. Muscular atrophy leads to the loss of basic life skills. With type 1 SMA, life expectancy does not exceed 1 year.

How many children live with SM (Muscular Atrophy of Verdnig-Hoffman)? With the use of IVL and enteral nutrition methods, you can save the life of a child for 1-2 years. It should be remembered that self-breathing, the baby's nutrition is impossible. Hofman-Verdnig Syndrome is the heaviest form of SM.

Late forms of SMA (SPINAL ATROPHY) leak easier. Muscle atrophy begins on the lower limbs. The patient complains about convulsions and pronounced weakness. Tremor and bezkiculation may appear. Symptoms are symmetrical on both sides. Muscles in the body of the body are gradually atrophized. Respiratory and respiratory muscles are rarely affected.

Atrophy of the muscles of the upper limbs (at Spinal Atrophy) begins the latter. Muscular atrophy will first affect the shoulders and adapters. Later, the disease passes to the forearm and muscles of the brush. Tremor also appears on the upper limbs, painful spasms.

Atrophy muscles in patients leads to disability. Each person has a disease in different ways. Muscular atrophy may not yet manifest themselves with active gymnastics and exercises. Progressive muscle tissue atrophy appears only at 1 and 2 types of disease.

SPINAL ATROPHY (SMA) and the diagnosis of PSMTs have similar symptoms. The spinal syndrome develops during injury only in certain muscle groups.

Symptoms of SMA in a child and an adult patient

The most severe clinical picture is developing at SMA type 1 (spinal-muscular atrophy in children). Developing SMA in a child from 6 months. The following signs are characteristic:

1. Lack of active motility in babies with spinal muscular atrophy. The newborn is sluggish, apatic, he eats badly;
2. The kid can not roll over, sit, crawl;
3. A reflex is reduced, a frequent accumulation of food appears, there are difficulties with the allocation of the lungs.

The forecast for spinal muscle atrophy in children with such a type of disease is unfavorable. Diagnose the disease can be diagnosed with characteristic clinical signs, the results of genetic analysis and electromyography.

Dubovitsy syndrome develops in 6-18 months. A healthy child who could crawl, sit, walk, gradually loses its skills. Over time, the weakness of the respiratory muscles appears, limbs are deformed, spine and chest.

Cugelberg-Vanther's syndrome is manifested after 18 months. The child is already able to stand, walk, performs complex motor actions. Patients do not cope with running, walking around the stairs. Later, violations of chewing and swallowing can join.

Adult muscle atrophy appears after 35 years. Its symptoms often resemble other neurological diseases. The disease significantly makes it difficult and leads to disability. An adult cannot move without a carriage, its socialization is reduced. The disease practically does not affect the life expectancy.

Differential diagnosis

Genetic analysis allows you to confirm or disprove the presence of the disease. But 5% of patients with SM, it turns out to be negative due to the atypical location of the mutated gene. In this case, the diagnosis is difficult to confirm, based only on the clinical picture.

Diseases with whom to differentiate SMA:

• Botulism of children's age;
• Muscular dystrophy of Duzhenna;
• Neuropathy;
• Myopathy (metabolic, congenital);
• X-clutched motto with breathing disorder.

For differential diagnostics, electromyography, computer and magnetic resonance imaging, blood tests for hormones are used.

Symptoms of different forms of disease

4 types of typical SMA and several atypical forms of the disease are isolated. The genetic disease is characterized by mutations in 5 chromosome in the form of deletion of the gene SMN1. With atypical amitrophy, the genotype may be the most diverse.

Typical motion starts in childhood. A atypical amyotrophy of Kennedy appears at the age of 30-50 years. And boys and girls are sick and girls. And Kennedy's disease is characteristic only for male.

Signs of Cugelberg-Vanther's Disease

The debit of symptoms appears at the age of 2 years. The child complains of fatigue while walking, running. Sweetness and instability of movements appear. Gradually, the patient's activity decreases, complex motor skills (running, lift along the stairs, sports games) is not available.

Over time, the patient is forced to move in a wheelchair. It develops contractures of large joints, thigh muscle atrophy, thoracic deformation and spine. This may be accompanied by the appearance of painful syndrome. Corrected by the timely appointment of gymnastics and leaf.

Typical signs:

• Wingid blades;
• "Duck" gait;
• Tremor language and upper limbs;
• Lack of tendon reflexes;
• Atrophy of major muscle groups.

Amiotrofia Kennedy

The disease is characteristic of adults after 30 years. They are mostly sick. In women, cases of pathology is not described. The first manifestations are characterized by fatigue of the icy muscles and the muscles of the thigh. The patient notices that he can not walk and stand for a long time.

Atrophy progresses slowly. About 10 years after the appearance of the first signs of pathology, patients can continue the usual way of life. Later, the disease passes to the upper limbs: tremor appears, the muscles of the head and neck are atrophy.

For amyotrophy, Kennedy is characterized by endocrinological changes. In adult men, the lack of sex hormones is determined, testicle atrophy and a decrease in sexual entraint occurs. The pancreas fabric is affected, sugar diabetes develops.

A characteristic symptom of the disease - the fasciculation of the perioreral muscles (twitching the corners of the lips and the drawing by the tube).

Distalma and SMU Vyulpiana

Distal SMA develops aged 20-50 years. For the disease, atrophy muscles of the distal departments of the upper limbs (brushes, forearms) occurs. Later develop violations on the legs. They are involved in the foot and legs. Over time, atrophy of the whole musculature of the limbs.

Sot Wüllpiana is characterized by atrophy of muscle groups of blades and muscles of the heads. The syndrome is developing after 20 years, but the likelihood of atrophy is preserved up to 40 years. During the disease, restriction of mobility of shoulder joints appears. The blades protrude and resemble wings. Hence the characteristic sign of the SMULPIAN - a symptom of "walled" blades.

Sumy of this type allows 30-40 years to remain active and maintain the mobility to a person. Only with a violation of the function of the extensors of stop and atrophy of the muscles of the towers is lost its ability to move. In general, this is a favorable type of the flow of amyotrophy, which does not lead early disabilities and does not become the cause of death.

Possible complications of SMA

The most frequent form of complications are respiratory disorders. Patients occurs atrophy of the muscles of the chest. When stopping, breathing should start immediately resuscitation and call ambulance. With the first type of muscle atrophy, respiratory stops occur after 1 year of life. Artificial ventilation of the lungs prolongs the life of the child.

Aspiration pneumonia is the second reason for deathal complications of the disease. In the kids with muscle atrophy, the cough reflex is disturbed and sputum is difficult. For its effective evacuation, the aspiration apparatus is better to have home. Effectively conducting respiratory gymnastics, immunization against influenza is required.

Pneumonia is infectious and treated with antibiotics.

In kids with SM, a swallowing reflex is disturbed. There is a frequent accumulation of solid, and then liquid food. When solid food in respiratory tract can develop acute respiratory failure. In this case, people who care for the child should know effective assistance techniques. Applied adapted for kids reception of gamelich. After the case of aspiration of a solid subject, it is necessary to show the child to the doctor.

Sumpories

SMA type	Genotype	Clinic
0 (zero)	No gene SMN 1 1 copy of SMN2 gene	Heavy face form Death of intrauterine or in the first month of life
1 (first) spinal aTROPHY. type 1 Verdnig-Hoffman disease	Deletion or mutation SMN1 2 copies of SMN 2 in case of Verdnigi	Syndrome "Sloped" child Heavy flow Death in the first 2-3 years of life (spinal muscle atrophy of type 1 is now treated, the results of life expectancy after treatment will be published in the next 5 years)
2 (second) sPINAL ATROPHY TYPE 2 Disease Dubovitsa	SMN1 After mutation turns into SMN2 SMN 2 is present in the form of more than 3 copies	Children sick from 1 to 2.5 years Motor skills are reduced Survival at 009SMA to 10-14 years
3 (third) sPINAL ATROPHY TYPE 3 Cugelberg-Vanther's disease	Copies SMN2 more than 3 May be mutations in the main gene	Appears after 30 years Mobility remains long Does not affect life expectancy
4 (fourth) sPINAL ATROPHY TYPE 4 Kennedy's disease	Long repeat of three tsAgan nucleotides in the androgen receptor gene Inheritance Captured S.X.-Hromosome	Only men are sick Symptoms start from 30 to 50 years

As can be seen, the symptoms of spinal atrophy of Verdnig-Hoffman are the most severe hereditary form of pathology. In the disease of the Verdyign, the syndromocomplex of the "sluggish" child is developing. With 1 type of work, the kid is immobile, lies in the "Frog" position, the muscular tone is reduced in all groups (typical for Spinal Atrophy), the hypermobility of the joints (typically for Verdnig's disease).

A child with a spinal amyotrophy of Verdnig-Hoffman is not able to acquire motor skills. Characterized by frequent surface breathing, the inability to take a deep breath. In case of Verdnig-Hoffman disease, the kid does not perform functional muscle samples.

The spinal Miotrophia of the Urdniga Goffman, as well as other types of muscle spinal atrophy not only the first type have pathogenetic treatment. The spinas preparation allows you to improve the motor skills of children even with a heavy form of SMA. The course of application is lifetime. The drug is used in the therapy of the disease of the Verdyigna, Dubovitsa and other types of amyotrophy.

Main treaties

Treatment of spinal amiotrophy includes:

• Medical gymnastics;
• Physiotics;
• Compliance with diet and nutrition;
• Support for vitamins and nutrients.

Muscular spinal atrophy is now treated with spinas preparation. It is registered in 2017 and approved in 2019 as an Orphan Drug by the Ministry of Health of Russia. At the beginning of therapy, the degree of atrophy is important. Its effectiveness is higher in the early principle of use of the drug.

Atrophy of the masses of muscles in mothers occurs as a result of the destruction of nervous cells that innervate muscles. The defect is due to the absence of a protein that ensures the survival of motor neurons. When the cells in the spinal cord are dying, they do not send a signal to muscles. As a result, there is an involution of the muscles.

The spinal medication treats spinal muscle atrophy by activating the sleeping SMN 2 gene. This oligonucleotide stimulates the generation of the necessary SMN protein to a normal level. This allows you to slow down the death of motor neurons.

The drug should provide a breakthrough in muscular atrophy therapy. How many children live with muscle atrophy of type 2? Not more than 5-7 years. And now the child will live much more. Doctors promise a complete reduction of symptoms in the early pending treatment. Such encouraging results gave tests of the drug and the application of it in practice. The presence of two (ricepals is not yet registered in Russia) drugs will help to assist children who have a diagnosis of SM-2 type.

Possible therapeutic strategies

The future is already here and now there are 2 workpieces from SM. True, the price of the annual course of treatment costs about 750,000 dollars. Some countries provide support to families where there is such a diagnosis. For example, in Italy and Greece, the child's treatment is at the expense of the state.

In our country, the budget of the Ministry of Health does not allow such spending. But substantial charitable funds that organize treatment for sick patients. In case of disease, children need to start treated as early as possible. This is the key to the success of high-quality disease therapy.

Medical therapy, diet and child nutrition

Modern domestic medicine proposes to use, improving neuromuscular conductivity (alpha-lipoic acid, l-carnitine, alpha-glyceluorophospholine).

To improve the conductivity of nerve endings, vitamins and dietary supplements are used (thiamine, pyridoxine, amino acid complexes). In addition, nootropics and vascular drugs are prescribed.

In atrophy, muscles are recommended, rich in vegetable and animal protein. Use cereals, low-fat meat, cereals, fermented milk products. Vitamins of the group are rich in spinach, Kohlrabi cabbage, broccoli. In the child's diet, fresh fruits and vegetables should be included.

The child is better feeding home food. Preparing need stew, boiled, baked products. You can make dishes for a couple. Be sure to adhere to the mode of meals.

Small portions should be used, but reusable meals (5-6 times a day). In the diet, vegetables and fruits must occupy 50%, meat and white fish 35%, cereals and other carbohydrates 15%.

Physiotherapeutic methods including massage

Electromensional stimulation courses allow you to stop muscles dystrophy. EMC devices are available for home use and allows you to train various muscle groups. It does not require effort from the patient. The device is attached to the skin and sends pulses to the fabric.

Other techniques (magnet, laser, electrophoresis, bioptrore) can be used to treat pain syndrome in contractures, spinal curvature or chest. Easy stimulating massage is also shown in SM. It allows the blood supply to individual muscles. It is applied by 7-10 sessions courses.

Folk remedies

Treatment with folk remedies:

• Application of compress from reed bilying;
• Treatment with calcium tincture;
• Using Mordovnik.

The compress from the pan's blizzard is used in atrophied muscles. Two jbzyr bowl is poured with boiling water and insist 30-45 minutes. The decoction is impregnated with gauze and lay it on an atrophied limb. After cooling, the grazing should be carried out with a massage of the limb from the distal department to the proximal.

Calcium tincture is prepared from fresh eggs. They need to be rinsed under water and pour acid. It is better to use lemon juice from freshly squeezed fruits. In this case, calcium is washed out of the shell and enters the solution. Dissolution takes 5-6 days. Then the solution must be taken after eating on a teaspoon 3 times a day.

Russian Mordovnik is used inside. 1-2% tincture of a plant is used. It should be taken courses after a meal of 20-30 drops.

New in the treatment of spinal muscular atrophy

Now there is an effective drug for the treatment of illness. The problem of families with SMA from Russia is that the course of the treatment of "spinas" is very expensive and unavailable in domestic medicine. Janssen is a pharmaceutical company that is going to withdraw the drug to the Russian market and ensure the availability of products from Biogen.

Robsiplam or RG7916 is an experimental preparation for CM. At the International Neurological Congress, clinical trial data were announced. Doctors noted the encouraging results of its use. An application for registration of the drug in the FDA has already been submitted.

Patient care

Relatives take care of the child. Often it is hard work. Therefore, it is necessary to help close, volunteers and other not indifferent people. As a patient and his relatives, psychotherapy sessions are needed and consulting a professional psychologist. It helps to cope with burnout when leaving for a sick child.

1. For the rehabilitation of the patient, it is necessary to use anti-gravity positioning. It is used while walking, in bed and on their hands from parents. His rules are trained by rehabilitologists. Special adaptations are used (high headboard, pillows, anti-cluster systems);
2. Gymnastics, leaf, stretching, exercises are performed by patients every day. In practice, the patient requires an assistant who owns the charging complex. Daily muscle group training is a pledge of the preservation of long activity;
3. Technical means of rehabilitation facilitate the movement of the patient with SMA, help socialization. For this, strollers, beds, vertalizers are applied;
4. To correct the postover and maintain joints, tutors, orthoses, corsets are used. They must be manufactured individually for each patient;
5. Hydrotherapy is useful for patients with SM. Desired to spend it daily. Water should be warm (37-38 degrees). Exercises can be combined with swimming.

Native patient must own the equipment of positioning, massage, know the LFC complex. Also closest you need to be able to provide first assistance in the urgent state. Parents should skillfully cope with additional means of rehabilitation and care (aspirator, IVL apparatus, a device for reserving the oral cavity). For them, schools, patient care courses.

Prediction of treatment and possible complications

The prognosis of treatment before the appearance of the Spina was disappointing. Children with SMA 0 type died in the first days of life. The life expectancy of the kids was no more than a month. With the first type, the child needed constant respiratory support. The average life expectancy was about 1 year, less often up to 2 years.

The effectiveness of the application of "Spina" gives hope to families with SM. Testing the drug has shown not only improvement of functions, but also the possibility of complete recovery. The results of remote observations will be after 2022.

Typical SM complications: bronchopneumonia, aspiration pneumonia, acute respiratory failure. For a sick child need constant care and round-the-clock observation. Only in this case can be an emergency help to the baby.

What is expected in the future

Despite the breakthrough in the treatment of the disease, the development of drugs from muscle atrophy continues. Scientists are looking for the opportunity to completely get rid of the defective gene. This contains the development of the following areas of genetic engineering:

• correction and substitution of the defective gene SMN1;
• enhancing the activity of the gene SMN2;
• protection of motioneons;
• muscle protection.

Genetic engineering uses the technology of introducing "vectors". Special viral "Vector" is developed in the laboratory. It enters the body, embedded in a damaged DNA fragment.

RCRZ (Republican Center for Health Development MD RK)
Version: Clinical Protocols MOR RK - 2018

Spinal muscular atrophy and related syndromes (G12)

Children's neurology, Pediatrics

general information

Short description

Approved
Joint Commission for Medical Services
Ministry of Health of the Republic of Kazakhstan
from "19" April 2019
Protocol No. 63.

Spinal muscle atrophy - a group of clinically and genetically heterogeneous hereditary diseases caused by the progressive degeneration of the motoneurons of the front horns of the spinal cord (1). The development of the disease varies from birth to adult. Is an orphan disease (2)
Etiology and pathogenesis:The genetic disease in which all types of inheritance (autosomal dominant, autosomal-recessive, x-h-included) are possible. The SMN gene is responsible for the development of spinal muscle atrophy of children's age with an autosomal-recessive type of inheritance (1.6)

Input part

Protocol name:Spinal muscle atrophy in children

Code (s) on μb-10:

MKB-10.
The code	Name
G 12.	Spinal muscle atrophy and related syndromes
G 12.0	Children's spinal muscular atrophy, I type (Verdigo-Hoffmann)
G 12.1.	Other hereditary spinal muscle atrophy
G 12.2.	Motor Neuron disease
G 12.8.	Other spinal muscle atrophy and related syndromes
G 12.9.	Spinal muscle atrophy uncomputed

Date of development / revision of the Protocol: 2018.

Abbreviations used in the protocol:

HELL	autosomal dominant
AR	autosomal recessive
GEFR	gastroesophageal reflux
Zhkt.	gastrointestinal
IVL	invasive lung ventilation
Kt.	cT scan
KFK	creatine phosfokineza
MRI	Magnetic resonance tomography
Nivl	non-invasive lung ventilation
PCR	polymerase chain reaction
RKI	randomized clinical study
SMA.	spinal muscular atrophy
Ultrasound	ultrasound procedure
EMG	electromyiography
MLPA.	multiPlex Dependent Probe Amplification
SMN.	sokr. From Survival Motor Neuron (Motonieron survival gene - English)

Users Protocol: Children's neurologists, neonatologists, pediatricians, general practitioners, rehabilitols, children's orthopedic surgeons, anesthesiologists-resuscitation, pulmonologists, clinical genetics.

The scale of the level of evidence:

BUT	High-quality meta-analysis, systematic Overview of RKK or large rock with a very low probability (++) systematic error The results of which can be distributed to the corresponding population.
IN	High-quality (++) systematic overview of cohort or studies Case-control or high-quality (++) cohort or studies Case-control with a very low risk of systematic error or rock with low (+) systematic error risk, the results of which can be distributed to the corresponding population .
FROM	Cohort or study case-monitoring or controlled study without randomization with a low risk of systematic error (+). The results that can be distributed to the appropriate population or rock with a very low or low risk of systematic error (++ or +), the results of which cannot be directly distributed to the corresponding population.
D.	A description of a series of cases or uncontrolled research or the opinion of experts.
G.C.P.	Best clinical practice.

Classification

Classification:

• Type-type spinal amiotrophy (spinal amyotrophy of early children's age, or Verdnig-Hoffman's disease).
• Spinal Amiotrophy II type (spinal amitrophy of children's age, intermediate form).
• Spinal Amitrofy III type (Kugelberg-Vanther's disease).
• Bulbospinal Amiotrophy of Kennedy (adult shape).
• Distal.

Diagnostics

Methods, approaches and diagnostic procedures (1,3,4,5-14)

Diagnostic criteria

Complaints: Practical absence or later formation of motor skills.

Anamnesis:

• SMY 1 type is characterized by the debut of the previous 6 months, the symptom complex of the "sluggish" child, the bell-shaped form of the chest, pronounced hypotension, areflexia, language champions and breathing problems. Patients usually die up to 2 years from respiratory failure resulting from intercourse infections.
• SMI II type is characterized by the beginning of the disease between the ages of 6. up to 1.5 years and slower progression, the type of inheritance is autosomal-recessive. The patients also have a symptom complex of the "sluggish" child, hypotension, areflexia, the fasciculation of the tongue and breathing problems. Such patients are as much as possible to sit independently, and they develop numerous contractures of large joints.
• SMI III type develops aged from 1.5 years, in most cases progresses slowly, the type of inheritance is autosomal-recessive. These patients can walk on their own. Patients usually have weakness in iliac, four-chapted and adductor muscles, hypotension, hypotlexia and language champions. Some of the patients of this group over time loss the ability to independently movement.
• SMI IV type (Kennedy Bullbospinal Amiotrophy, form of adults) manifests itself on average for 4 decades of life with the weakness of bulbar muscles (dysfagia, dysarthria), followed by the adherence to the weakness of the proximal sections of the limbs, the weakness of mimic muscles, atrophy and faccification in the language, generalized firecriction, Krampi, Postural tremor, sensory polyneuropathy. Often characterized by gynecomastia, a decrease in sexual function, hypogonadism, spermatogenesis disorder, infertility, diabetes mellitus. Type of inheritance - x-hooked recessive.

Physical examination: Clinical manifestations of damage to the motor neurons of the spinal cord, namely a sharp discrepancy between the motor function of the age norm.

• Changes in a neuromuscular system: muscle fibrillations, generalized muscle hypotension, muscle atrophy and fascicullary twitching in the muscles of the back, torso, proximal (less often in distal) departments of the upper and lower extremities; hyphotexia up to the area;
• Changes in bone-Chocked system: thoracic deformation, spinal deformation (kifoscolyosis), joint contractures, foot pathology.
• Violation of respiratory function: as a result of disruption of coughing and swallowing, hypoventilation during night sleep, underdevelopment \\ chest deformation, private infectious diseases due to disruption of the evacuation of the secretory separated from the respiratory tract.
• Dysfunction GTC: Switching disorders (including due to bulbar syndrome) Motoric disorders of the tract, which include constipation, delay in the evacuation of the contents of the stomach and potentially life-threatening gastroesophaginal reflux (GEFR).
• Pain syndrome: As a result of the pathology of the musculoskeletal system, osteopia and fractures.
• Growth and hypoxian / hypertrophy.
• Sensitivity impairment: Not typical.
• Violations of psychoreche and cognitive development: Not characteristic

From a practical position, it is advisable to differentiate patients based on their functional status:

• Children who cannot sit without assistance ("Lying patients");
• Children who can independently sit, but cannot walk without assistance ("Sitting patients");
• Children who can independently walk ("walking patients").

Laboratory research:

• General analysis of blood and urine: No specific changes.
• Biochemical blood test: levelKFK can be normal or slightly elevated. Interpretation to estimate the delay of the propulsion system:

- greatly elevated:\u003e 50 000 UR / L
- Average elevated: from 3000 to 50,000 units / l
- slightly elevated: from 180 to 3000 units / l
- Normal: from 24 to 180 U / l

• in some cases, it is advisable to a liquorogram - Increase the amount of protein by 25% or more.

Tools:

• Electromiography (EMG): Rhythmic champions with amplitude amplitude up to 300 μV and 5-35 Hz frequency (Rhythm Paloscol). The speed of the pulse along peripheral motor fibers can be both normal and slightly reduced by secondary denervational changes. For children 1 and 2 types has a smaller diagnostic value than for other types.
• Ultrasound and MRI muscle: signs of fat substitution of muscle tissue.
• Genetic tests - Designed to establish a diagnosis of SM, forecasting and selecting therapeutic approaches. The lack of full Copies SMN1 confirms the diagnosis, information about SMN2 copies is important for the forecast and select therapy.

Test for (mutation) gene deletionSMN., Conducted by MLPA (Multiplex Dependent Probe Amplification) - determines the number of copies of SMN1 and SMN2 - the Golden Diagnostic Standard.

• Quantitative PCR: Identifies the homozygous deletion of SMN1, but does not allow to calculate the number of copies of SMN1 and SMN2.

Homozygous deletion 7 of the exon gene SMN1 (if there is no or no exon mutation 8) confirms the diagnosis of SMN-associated SMA (5Q-SMA). Other diagnostic tests must be assigned only with the negative result of the SMN gene.

Diagnostic algorithm:


Notes: EMG - electromyography, NMP- nervous muscular conductivity; KFK - creatinophosphokinea; NMZ-nervous muscular diseases

The dependence of the clinical picture of SMA from the number of copies of genesSMN.1 I.SMN.2.

SM Type	Number of copies of genes	Features of a clinical picture
Wagon	Full absence of both genes SMN1 and SMN2	Female situation
CMA type 0.	No SMN1 gene and 1 copy of SMN2 gene.	Heavy muscle weakness, death comes up to 1 month
CMA Type I.	Predominantly deletion of SMN1 or several Missence mutations in SMN1; SMN2 Usually 2 copies.	The symptom complex of the "sluggish" child, death comes up to 2 years.
CMA Type II.	Mutations convert the SMN1 gene in SMN2; Copies gene SMN2. > 3 copies;	Can sit on their own.
CMA Type III	Copies gene SMN2. > 3 copies; Missens may meet point mutations.	Can walk on their own.

Indications for consulting professionals

Specialist	purpose
Children's neurologist	Clinical diagnosis of the disease, direction on genetic and paraklinic diagnostics. Development of a short-term and long-term plan of maintaining and rehabilitation. Coordinator of the multidisiciplinary team of specialists, monitoring and evaluation of the effectiveness of a comprehensive treatment and rehabilitation plan. Deciding on the appointment of specific therapy.
Geneticist	Genetic diagnosis verification. Medical and genetic counseling of the family, informing about the methods of prenatal and pre-compact diagnostics.
Pediatrician	Diagnosis and correction of violations by the insecurity of organs. Monitor physical, somatic and nutritional status.
Pulmonologist / Respiratory Support Specialist	Diagnosis of disturbances of the respiratory system, the development and implementation of the treatment plan and long-term churation in case of their presence
Anesthesiologist-resuscitator (Children's)	Diagnosis of violations of the respiratory system of patients who need to carry out non-invasive ventilation of the lungs (NIVL), the correction of water-electrolyte metabolism and protein status against the background of the mass deficit of a severe body.
Gastroenterologist	Diagnosis and correction of disorders of the digestive system, the development and implementation of the treatment plan and long-term chicken in the case of their presence.
Nutritionist	Solving issues of selection and sale of diet
Orthopedist	Diagnosis of disorders of the bone-articular system, conservative correction of the pathology of the spine, joints, stop; Surgical correction. Selection of orthheastes / tutor and other necessary devices.
Rehabilitol (incl. Specialist of the FFC)	Development and implementation of complex rehabilitation (including motor). Training of the patient's family.
Psychologist	Qualifications of psychological disorders, development and implementation of a treatment plan and long-term chicken in the event of their presence. Family psychological counseling

Differential diagnosis

Differential diagnosis and substantiation of additional research

Differential diagnosis of SM and other spinal cord lesions

Diagnosis Sign	Lateral amyotrophic sclerosis	Vertebrogenic cervical myelopathy	Siringomyelia
Clinic	Peripheral paresis, high tendon periosal reflexes, fibrillation, muscle beycic chictionations, defeat of the cranial brain nerves (V-XII), atrophy	Peripheral paresis and sensitivity disorders in the innervation zones of cervical segments dominate the symptoms of ischemic lesion of the motor structures of the cervical thickening	Distal atrophy, muscle tone and reflexes are reduced, pain syndrome, disconnecting sensitivity disorders, vasomotor and trophic disorders, diesel status
Flow	Preliminary	Slow progressive	Slow progressive
Radiography	Without features	Cervical department - pronounced phenomena of osteochondrosis and narrowing of the spinal canal	Cyphoscolliosis, added ribs, not an infection of the cervical and lumbar vertebrae, assimilation of the Atlanta with a tight bone, basilar impression

Other rare forms of spinal muscle atrophy are presented in the table. Some of them have isolated descriptions in world literature, many of which are specific for specific isolates.

Differential diagnosis of proximal autosomal-recessive SM and other forms of SMA

Disease	Protein / Gen.	Abbreviated name (eng.)	Type of inheritance	Lock	Number BOmim
Infantile spinal muscular atrophy with arthrogripposis	Revivitin-activating enzyme 1 (UBE1)	XL-SMA; SMAX2.	X-clutch	XP11.23	#301830
Proximal SMA with blood inheritance and adult debut	Vapb.	Finkel type, or late adult type	HELL	20Q13.32.	#182980
SMA: congenital, unpropressive, with a predominant lesion of the lower extremities \u003d bladder peronealma	TRPV4.	SPSMA.	HELL	12Q24.	#600175
Early SMA with contractures	Double D, Drozophila, Homolog 2 (BICD2)		HELL	9Q22.31	#609797
SMI with dominant atrophy of the lower belt limbs	Dienein, cytoplasmic 1, heavy chain 1 (DYNC1H1)	Sma-led.	HELL	14q32.31	#158600
Distal CMA, X-Coupled 3	ATFA, CU ++ -Transporting, Alpha Polypeptide (ATP7A)	SMAX3.	X-clutch	Xq21.1	#300489
Distal infantilema with a diaphragm paralysis	Immunoglobulin μ-related protein 2 (IGHMBP2)	DSMA3; SMARD1; HMN 6.	AR	11Q13.3.	#604320
	Vaccinia-coupled Kinaz 1 (VRK1)	PCH1A.	AR	14q32.2.	#607596
Pontocerabellar hypoplasia with	Exosomes Component 3 (EXOSC3)	PCH1B.	AR	9p11	#614678
Lower Motoinone Syndrome with Early Children's Benefits	Plekhg5.	DSMA4.	AR	1p36.31	#611067
Distal Motor Neuropathy with Early Adult Debut	DNAJ / HSP40 homolog, subsemia B, Member 2 (DNAJB2; HSJ1)	DSMA5; Dhmn.	AR	2q35	#614881
Proximal SMA with a progressive myoclone epilepsy	N-acylsfiningosine amidogydolaza 1 (ASAH1; acid ceramidase)	SMA-PME; SMAPME.	AR	8p22.	#159950
Distal hereditary Motor Polynevropathy type of Gerash		DSMA 2; Hmnj.	AR	9P21.1-P12.	#605726
Lower Motonieron Syndrome with Late Adult Debut		Smaj.	HELL	22Q11.2-Q13.2.	#615048

Treatment

Preparations (active substances) used in the treatment

Treatment (ambulatory)

Tactics of treatment on an outpatient stage

Treats of treatment:
- Improved patient's neurological and somatic indicators
- correction of motor disorders, prevention of contractures;
- prevention \\ treatment of complications from organs and organism systems (respiratory, digestive, etc.);
- Psychological support for parents (family counseling);

Non-drug treatment (mode, diet, etc. radiation);
General principles:
A) is carried out taking into account the functional status of the patient (see above the section "Physical examination") and the degree of progression of the disease
B) with mandatory training of family members of the patient skills of everyday care

Directions of therapeutic impact:

1) Respiratory Prevention

Tasks

Events

Normalization of gas exchange (including with the use of respiratory support tools) Improving sleep quality Lightweight home care Minimize hospitalization and treatment in the intensive care unit

1. Teaching the patient's family skills of everyday care, techniques for removing the pulmonary secret, actions in the case of acute diseases. 2. Developed joint with parents of a plan with minimum and maximum assistance to the patient 3.Monitoring of patency (evaluation of the coulting, chdd, etc.) and respiratory sane, incl. Using special means (suction) 4. Regular polysomnography (the multiplicity of the conduct determines the attending physician) 5. Regular pulse oximetry (the multiplicity of holding determines the attending physician) 6. Regular inspection (incl. X-ray) spine and bones of limbs in order to solve the issue of correctional intervention (the multiplicity of conducting the attending physician) 7. Solving the issue of applying ventilation with constant positive pressure (HDPD), ventilation with 2-hurry positive pressure (VDD) and / or non-invasive pulmonary ventilation (NIVL) (in the framework of monitoring of the respiratory function- Fig. 1)

Picture 1.

2) Solving nutritional issues

Tasks	Events
Provide a regular admission to the organism of the necessary nutrients Provide regular extinguishing from the body of life products Weight control	1. Patient family learning to the skills of the general situation to achieve independent nutrition, incl. Using special means. 2. Changes in food consistency. Semi-hard food can compensate for chewing weakness and reduce food duration. Thick fluids are safer with aspiration, the more flowable. 3. Using active food additives and specialized medical nutrition in case of detected food diet. 4. Solving the issue of probation 5. Singing Weight Setting
Prevention gastroesophaginal reflux (GER) is an important pathology that determines mortality and incidence in sick patients. Fat food details the gastric emptying and increases the risk of GER	1. On the early Symptoms of GER (urge on vomiting, belching, rumbling in stomach after meals). 2. EGDS Study of the Upper Distributions of the tract 3. Motoric and stomach motor research (incl. Radiation diagnostics)

3) Solving the problems associated with the bone-muscular system

Tasks
Maintenance \\ Increase available motor activity Prevention of contractures, fractures, painful syndrome, as the consequences of the latter.
Events (general principles)
1. Treatment of the patient's family to the skills of therapeutic physical education. 2. Monitoring (multiplicity determines the attending physician) volume of available movements, tone and muscle power, bone density (densitometry) 3. Evaluation of the need for orthopedic (including surgical) correction \\ prosthetics. 4. X-ray (multiplicity determines the attending physician) 4. Conducting kinesiotherapy
Events depending on the functional status of the patient
"Lying"	Maintaining optimal poses Stimulation of everyday activity (including with special fixtures) Solving the issue of concretion in order to preserve the volume of movements and prevent painful syndrome. Selection of wheelchairs, providing maximum functional independence and comfort Prosthetics of limb functions - mobile support for upper extremities or elastic materials increasing the volume of active movements and functionality Control pain
"Sitting"	Ensuring the ability to safely move with a wheelchair Planned Using Mobile Upper Limit Support Devices Development of physical strength and endurance Encouraging stay in a standing position, incl. The use of lightweight sedable and knee-anxicotive-stop orthopedic apparatus with a load on foot or orthopedic equivalent devices that allow standing and walking with other persons Application Ortesov
"Walking"	Use the wheelchair to move over long distances. Kinesotherapy and active pastime to preserve endurance and independence and / or prevent / reduction of disability. Walking, if necessary using auxiliary devices, should be encouraged. Regular exercises must be encouraged in every way, because Support the physical shape and endurance of the patient. Exercises may include swimming, various types of water exercises (aquaterapy), hippotherapy and adaptive sports. Activities for adaptation of home (and other surrounding) settings to ensure maximum independence of patients through the security and accessibility of all the funds they need. Application Ortesov

4) relieving acute situations (sudden deterioration of respiratory functions)

Tasks

Events

Normalization of gas exchange Hypoglycemia prevention

1. Treatment of the patient's family diagnostic skills and correction of patients at home in case of acute situations 2. Monitoring blood gases 3. Cleaning the respiratory tract 4. Conducting oximetry 5. Application of NVL, incl. with the use of oxygen and evaluating its effectiveness 6. Solving the issue of trachea intubation and mechanical ventilation of the lungs 7. Solving the issue of tracheotomy 8.Optimization of the power mode, resolving the question of parenteral nutrition.

Tactics of treatment on an outpatient level

Non-drug treatment:

• Mode:Protective mode; compliance with the optimal humidity and temperature regime in the room; fresh air access; Prevention of bacterial and viral diseases, contact restriction with infectious patients
• Diet:Full foods enriched with proteins and vitamins, receiving biologically active additives to food. The use of semi-solid food and thick liquids. With SMA 0-1 type: therapeutic specialized milk mixtures enriched with amino acids and proteins. With probation feeding and through Gastrostom: therapeutic specialized liquid nutrition.
• Care.Skin care and mucous membranes; Sanitation of oral and nasal cavities, upper respiratory tract; Preventing beds.

Medical treatment (1-7 , 10-14):

Drug group		Mode of application	Level of evidence
		Inside	FROM
Metabolic preparations and vitamins	Coenzyme Q10 -	Inside	FROM
Metabolic preparations and vitamins		Intramuscular	FROM
Metabolic preparations and vitamins		Intramuscular	FROM
Metabolic preparations and vitamins		Inside	FROM
Metabolic preparations and vitamins		Intramuscular	FROM
	Salbutamol 2-4 mg 4 times a day; Maximum dose - 32 mg / day	Inside or in the form of an aerosol	IN

Surgical intervention: no

Further maintenance:

• Dispensary observation in the attached medical organization at the place of residence.
• Inspection by experts on time and by testimony. In the event of a severe condition of the patient, an acute infectious disease or a non-diamptulator stage - inspection by specialists and conducting diagnostic procedures at home.
• Symptomatic and maintenance therapy for basic and accompanying diseases.
• Continuation of rehabilitation activities: LFK, kinesiotherapy, respiratory support in a daytime hospital of a medical organization, at home with the help of an instructor of the LFC, medium medical personnel, trained family members.

• Positive dynamics of functional status;
• Lack of complications;
• Lack of hospitalizations in the separation of intensive therapy.

Treatment (hospital)

Tactics of treatment at the stationary level

Non-drug treatment:
General principles:

• It is carried out taking into account the functional status of the patient (see above section "Physical examination") and the degree of progression of the disease;
• With the obligatory training of family members of the patient, daily care skills.

Medical treatment:
Symptomatic: Metabolic preparations applied in the form of courses are shown.

List of basic medicines:

List of additional drugs:

Drug group	International Non-Patient Name of LS	Mode of application	Level of evidence
Metabolic preparations and vitamins	L-carnitine up to 1000 mg / day courses for 2 months	Inside	FROM
Metabolic preparations and vitamins	Coenzyme Q10 - 30-90 mg / day courses for 2 months	Inside	FROM
Metabolic preparations and vitamins	Pyridoxine hydrochloride, ampoules, 1 ml 5%	Intramuscular	FROM
Metabolic preparations and vitamins	Tiamine chloride, ampoules 5% 1 ml	Intramuscular	FROM
Metabolic preparations and vitamins	Folic acid, tablets 0,001	Inside	FROM
Metabolic preparations and vitamins	Cyanocobalamin, ampoules 1 ml 200 μg and 500 μg	Intramuscular	FROM
Selective agonists β 2 -adrenoreceptors	Salbutamol. 2-4 mg 4 times a day; Maximum dose - 32 mg / day	Inside or in the form of an aerosol	IN

Surgical intervention:

• Tenotomy - with a pronounced deformation of the foot and ankle joint
• Spondylodez - a type of surgical intervention on the spine, aimed at immobilizing adjacent vertebrae due to their splicing. Purpose: Preventing the further deformation of the spine, improving the balance in a sitting position, improving the function of the lungs, improving the quality of life of patients. Indication: Scoliotic spinal deformation. The operation is carried out after the end of the spinal growth, in children over 12-13 years old. Contraindications: Decompensated Light Function, Dosage Allergies, Bronchial Asthma.
• Gastrostomy - a surgical operation consisting in creating an artificial entrance to the cavity of the stomach through the front abdominal wall. Purpose: Feeding a patient if you are impossible for food through your mouth. Indication: Dysphagia, GEFR, long-term probe feeding, exhaustion due to insufficient food intake.
• other interventions by solving Multidiscillar Consilium

The decision on surgical intervention solves a consilium with the participation of an orthopedic surgeon, a gastroenterologist, a children's neurologist, a pulmonologist, and other specialists, with the involvement of the patient's parents / proxy. The decision is made on the basis of the assessment of the current clinical and functional status of the patient, the data of spirometry, the results of MRI / CT, radiography, ultrasound and analysis of risk / benefit ratio.

Common contraindications:

• Pronounced hypotrophy
• No stable adequate pulmonary ventilation

Perioperative care
In patients with SMA, there is a large risk of post-class complications, which can lead to long-term intubation, and a hospital infection, tracheotomy and death. It is important that the condition of the respiratory function in the patient is optimized before the operation. Preoperative assessment is shown, including the following activities:
. Measuring the respiratory function and cough efficiency;
. X-ray of the chest organs;
. Identification of breathing disorders during sleep;
. Identification of complicating factors, including ankylosis of jaws, orofaringy aspiration, gastroesophageal reflux, state of nutrition and the presence of asthma.
If the results of the study of the respiratory function and / or the study of the sleep pathological, then before surgical intervention, the Night Nivl and the application of methods for improving the refreshing is shuddered. The patient should be familiar with these techniques prior to surgery. If it is possible to make it difficult to perform intubation due to jaw ankylosis, intubation must be performed under the control of fiber optic bronchoscopy

Further maintenance:
Postoperative care includes the following activities:

• If the patient is able to extend the contents of the respiratory tract and has a relatively preserved power of the respiratory muscles, then the risk of postoperative complications does not exceed those in patients with another pathology.
• If the weakness of the respiratory muscles takes place before the operation begins, this patient needs continuous monitoring and control of respiratory functions.
• If the patient needed respiratory support to the operation, then their immediate application in the postoperative period is necessary. Preoperative auxiliary artificial ventilation of the lungs during sleep and similar auxiliary artificial ventilation of the lungs immediately after the operation.
• Extbation and transition to NWL should be planned as an intermediate stage to return to the preoperative respiratory support system. If the patient needed constant respiratory support before the operation (by NVL or through the tracheos) or during operation, minelaxants were used during operation, its translation into the intensive care unit is mandatory.
• It is desirable that the patients have their own individual devices for NIVL and / or aspirators for use in the postoperative period, since the hospitals may have a limited number of such devices.
• Oxygen in SMA patients should be used with caution. Secondary hypoxhemia due to hypoventilation may be confused with hypoxhemia due to other reasons, such as blockage of mucus or atelectasis. Control of carbon dioxide concentration at the end of the exhalation or inside control CO 2, or the analysis of the content of gases in arterial blood will help choose the correct oxygen application mode.
• Adequate anesthesia will prevent hypimensing in the early postoperative period associated with immobilization. The depth of anesthesia should be selected, taking into account the minimization of the braking of the respiratory centers. Temporary gain of respiratory support may be necessary to control postoperative pain.

Care for patients in a sharp period (acute respiratory disease, pneumonia, sudden deterioration of respiratory functions).
The purpose of the care of patients in a sharp period of the disease is the normalization of gas exchange by purifying respiratory tract. Constant monitoring of the gas composition of blood and respiratory function allows you to carry out adequate respiratory therapy and avoid the atelectasis of pulmonary fabric. To enhance the flipping, manual methods or mechanical devices, postural drainage, chest cinematherapy are used. The effectiveness of these measures is estimated in the indicators of oximetry.
Nutrition Sumy patients with acute pathology (acute respiratory disease, pneumonia, sudden deterioration of respiratory functions).
Sickness sicks, especially sleeping and seating, are more prone to hunger hypoglycemia. This category of patients is advised to avoid long starvation, especially in sharp periods of diseases. To cover the energy costs in the acute period, it is necessary to calculate the power and start within 4-6 hours from the moment the patient is proceeded into the hospital. In the absence of contraindications, preference should be given to enteral nutrition, if necessary, connect complete or incomplete parenteral nutrition.

Treatment Efficiency Indicators:

• Verification \\ exclusion of the diagnosis of SMA;
• In the event of an admission to the stage of active rehabilitation or surgery: positive changes in the functional status of the patient.

Hospitalization

Indications for hospitalization indicating the type of hospitalization

Indications for planned hospitalization:

• Carrying out genetic diagnostics to confirm \\ MSI exceptions;
• Implementation of the stage of active rehabilitation using funds inaccessible on the outpatient stage;
• Surgical (orthopedic) correction.

Indications for emergency hospitalization:

• The inability to relieve acute state (respiratory failure, pain syndrome) in outpatient conditions.

Information

Sources and literature

1. Meeting Protocols of the Joint Commission on the Quality of Medical Services MR RK, 2018
   1. 1. Vlodais D.V, Kharlamov D.A., Artemieva S.B., Belousova E.D. Federal clinical recommendations (protocols) on the diagnosis and treatment of spinal muscle atrophy in children. 2013 [Electronic resource] https://mzur.ru/upload/pinal muscular atrophy.doc 2. Ogino et al. Genetic Risk Assessment in Carrier Testing for Spinal Muscular Atrophy // American Journal of Medical Genetics 2002; 110: 301-307 3. Ingrid E. C. Verhaart, Agata Robertson, Ian J. Wilson, Annemieke Aartsma-Rus et al. PREVALENCE, INCIDENCE AND CARRIER FREQUENCY OF 5Q-LINKED SPINAL MUSCULAR ATROPHY - A LITERATURE REVIEW. Orphanet Journal of Rare Diseases 2017 12: 124. 4. Mercuri et al. Diagnosis and Management of Spinal Muscular Atrophy: Part 1: Recommendations for Diagnosisal Care // Neuromuscular Disorders 28 (2018) 103-115 5. Finkel et al.Diagnosis and Management of Spinal Muscular Atrophy: Part 2: Pulmonary AND ACUTE CARE; Medications, Supplements and Immunizations; Other Organ Systems; And Ethics // Neuromuscular Disorders 28 (2018) 197-207 6. Finkle RS, Serjesen T, Mercuri E; ENMC SMA Workshop Study Group (2017) '218th ENMC International Workshop: Revisiting The Consensus on Standards of Care in SMA. Naarden, The Netherlands, 19-21 February 2016 '. Neuromuscular disorders. 27 pp. 596-605. doi.org/10.1016/j.nmd.2017.02.014. 7. Wang CH, Finkel RS, Bertini ES, Schroth M, Simonds A, Wong B, Aloysius A, Morrison L, Main M, Crawford To, Trela \u200b\u200ba Participants of the International Conference on Sma Standard Of Care (2007) 'Consensus Statement For Standard of Care in Spinal Muscular ATROPHY '. Journal of Child Neurology, 22 (8), PP.1027-49 doi.org/10/1177/0883073807305788 8. Chong, Jx, Ouwenga, R., Anderson, RL, Waggoner, DJ, Ober, C. A Population-Based Study Of Autosomal-recessive Disease-Causing Mutations in a Founder Population. Am. J. Hum. Genet. 91: 608-620, 2012 9. ARKBLAD EL, DARIN N, BERG K, KIMBER E, BRANDBERG G, LINDBERG C, HOLMBERG E, TULINIUS M, NORDLING M. Multiplex Ligation-Dependent Probe Amplification Improbe Diagnostics in Spinal Muscular Atrophy. Neuromuscul disord. 2006; 16: 830-838. 10. Messina S, Pane M, De Rose P, Vasta i, Sorleti D, Aloysius A, Sciarra F, Mangiola F, Kinali M, Bertini E, Mercuri E. Feeding Problems and Malnutrition in Spinal Muscular Atrophy Type II. Neuromuscul disord. 2008; 18: 389-93. DOI: 10.1016 / J.Nmd.2008.02.008. 11. Bertini E, Burghes A, Bushby K, Estournet-Mathiaud B, Finkel RS, Hughes Ra, Iannaccone St, Melki J, Mercuri E, Muntoni F, Voit T, Reitter B, Swoboda KJ, Tiziano D, Tizzano E, Topaloglu H, Wirth B, Zerres K. 134th ENMC International Workshop: Outcome Measures and Treatment of Spinal Muscular Atrophy, 11-13 February 2005, Naarden, The Netherlands. Neuromuscular disorders. 2005; 15: 802-816. DOI: 10.1016 / j.nmd.2005.07.005. 12. W David Arnold, Darine Kassar, John T Kissel. Spinal Muscular Atrophy: Diagnosis and Management in a New Therapeutic Era. Muscle Nerve. 2015 FEBRARY; 51 (2): 157-167.doi: 10.1002 / Mus.24497. 13. Seliverstov et al. Spinal muscular atrophy: concept, differential diagnosis, treatment perspectives [electronic resource] https://www.neurology.ru/sites/default/files/assets/documents/2016/01/nb-3-2015-09.pdf?download \u003d 1 14. https://www.e.europa.eu/en/documents/product-information/spinraza-epar-product-information_en.pdf 15. https://www.drugs.com/history/spinraza.html

Information

Organizational aspects of the Protocol

List of protocol developers with qualifying data:

1. Jacksibaeva Altynshash Khairullayevna - Doctor of Medical Sciences, Professor of the Department of Neurology NAO Medical University of Astana.
2. Mysaliyeva Bakhyt Zhusupzhanovna - Master of Medical Sciences, PhD Doctoralist MKTU. H.A. Yassavi, Children's neurologist of the highest qualification category, Member of the Association of Children's Neurologists' Association, Consultant of "IMIRGE SEN".
3. Zhumakhanov Dauren Bakhytbekovich - Children's neurologist / Neurophysiologist, Director of Neurophysiology Center NeuroLab.
4. Nurmagambetova Baghila Kuralbaevna - Candidate of Medical Sciences, Children's anesthesiologist-resuscitation of the Children's Surgery Department of the KF "UMC" "National Scientific Center of Motherhood and Childhood".
5. Zhetymkarinova Gauhar Yerlanovna - Clinical Pharmacologist CF UMC "National Scientific Center of Motherhood and Childhood"

Indication for the absence of conflict of interest: not.

Reviewers:

1. LEPENSOV MARZHAN Makhmutovna - Doctor of Medical Sciences, Professor, head of the Department of Neurology with a course of medical genetics Kazmuno, President of the Association of Children's Neurologists, a member of the European Society of Children's Neurologists, International Society of Children's Neurologists.

Protocol revision conditions: Revision of the Protocol 3 years after its publication and from the date of its entry into force or in the presence of new methods with the level of evidence.

Attached files

Attention!

• By self-medication, you can apply irreparable harm to your health.
• The information posted on the MedElement website and in MEDElement mobile applications, "Lekar Pro", "Dariger Pro", "Diseases: Therapist's Directory", cannot and should not replace a full-time doctor consultation. Be sure to contact medical facilities in the presence of any diseases or disturbing symptoms.
• The choice of medicines and their dosages should be stated with a specialist. Only a doctor can prescribe the necessary medicine and its dosage, taking into account the disease and the state of the patient's body.
• Website MedElement and Mobile Applications "MedElement (Medleylement)", "Lekar Pro", "Dariger Pro", "Diseases: Directory of Therapist" are exclusively information and reference resources. The information posted on this site should not be used for unauthorized changes to the doctor's prescriptions.
• The editorial office of MedElement is not responsible for any damage to health or material damage resulting from the use of this site.

The spinal amyotrophy (spinal muscular atrophy or SMA) is an incurable, almost always inherited disease caused by the Mutation of the gene in the 5th chromosome.

Mutation of SMA gene leads to a lack of protein, which is necessary for constructing protein RNA structures, and to insufficient development of transverse muscles, mainly lower extremities, as well as the cervical and head.

The disease can manifest itself from the moment of birth, and even when the fruit is still in the womb, and in any period of life. Newborn, spinal amyotrophy, most often leads to early death, but in some cases it can have soft forms, mainly in old age. Consider in more detail the features of this pathology.

Spinal Amiotrophy - all about illness

History and statistics

SMA - a rather rare disease, opened by the German doctor in 1891, is sick of one person out of 6 - 10 thousand, but the carrier of the recessive gene gene is every 50th person.

In 1898, Verdnig and another scholar Hoffman found that the cause of SMA is a degenerative defeat and an insufficient number of motor (motor) neurons of the front spinal cord - SMN (SURVIVAL MOTOR NEURONS).

Already in the 20th century (in 1956), other Scientists Cugelberg and Vanderder discovered less malignant, with softer manifestations, the form of Misa, which is sick in juvenile and adult age.

Type of inheritance in spinal amiotrophy

The disease can be inherited by any of the types:

• autosomal dominant;
• autosomal recessive;
• X-clutch dominant;
• X-clutched recessive.

In this regard, it is classified a lot of different forms of SM.

Children's form of CMA is inherited by autosomal-recessive type: if both parents are carriers, then the fourth part of their offspring will be ill.

Autosomal dominant type of SM inheritance leads to a disease manifestation in children with a probability of 50%, even if only one parent is sick.

Types of spinal amyotrophy

Spinal muscular atrophy is divided into four forms:

• Infant (I) - spinal muscular atrophy of the Vordnig-Hoffmann: diagnosed from the moment of birth to six months.
• Intermediate (II) - Dube disease: from seven months to one and a half years.
• Youth (III) - b. Kügelberg-Vallanger: after one and a half years.
• Adult (IV): After 35 years.

Symptoms of spinal-muscular atrophy

General symptoms with SMA:

• defeat the proximal (medium) muscles and fascia;
• preservation of sensitivity in most clinical cases;
• delays mental and mental development in spinal muscular amyotrophy is extremely rare;
• it is possible with some types of atrophy not only muscles of limbs, but respiratory, chewing and swallowing.

Severity SMA.

• The most severe and unfavorable is considered a SMI of the first species (infant) - the spinal amyotrophy of Verdniga - Hoffman, in which children are not able to make active movements, keep their head, sit on their own. With great difficulty, feeding is given to the baby, as it is difficult for him to suck milk and swallow it.
• Dubovitsi disease is less malignant (II SMI intermediate form): With her, children are able to sit, keep their head, but they are still unable to walk.
• The least heavy is the youthful form: despite the muscular weakness, the child is able to learn how to walk, but the disease, though slowly, but progresses and can lead to early disabilities.
• The fourth adult form of SMA can lead due to the weakness of M - C proximal departments to the impossibility of independent movement, the fallout of reflexes, but the forecast in the ratio of the duration of life remains favorable.

Other types of spinal muscle atrophy

In addition to mutation in genes causing the defeat of the proximal muscles, there are similar pathologies, with different types of inheritance, leading to muscle atrophy and fascia of distal (end departments).

The list of them is quite large, minimize the disease in a small table:

SMIT name	Type of inheritance	Features and symptoms
Smax1.	X-core recessive	It is mostly observed in the elderly, affects the burbar nerves of the skull, causes downward paralysis.
Smah2.	X - clutch. recessive	Congenital aggressive form leading to death up to 3 months. Causes weakness, area, contractures and fractures.
SMAX3.	X - clutch. recessive	Amazes mostly boys. Atrophy of all distal muscles. Slow rapid symptoms
Distal DSMA1	autosomal - recessive	Congenital, striking basically hand, heavy respiratory disorders are possible.
DSMA2 dSMA2 - DSMA5	autosomal - recessive	All four forms are characterized by slow progression, DSMA5 is diagnosed with young.
Distal mothers of two types: VA and VB (DSMAVA and DSMAVB)	autosomal dominant	Mostly atrophied upper limbs.
DSMA type 2d.	autosomal - recessive	Youth and adult disease with slow development: proximal, and distal M - Caras are first in the legs, then in their hands.
DSMA Type 7A.	autosomal dominant	Very rare adult shape with damage to voice ligaments.
DSMA Type 2A.	autosomal dominant	Variety of Charcot Disease (Allle Type)
Juvenile SMA (type HMN1)	autosomal dominant	Meets in Youth
Congenital spinal amyotrophy	autosomal dominant	Impairment of innervation and atrophy M - C hips, stop, knees with contracture and deformation; Sometimes voice ligaments are affected.
SMA Finkel	autosomal dominant	It begins preferably at 35 - 37 years, but there are cases of disease and childhood. Slowly develops at the beginning, and then in hand. Activity and reflexes are reduced, involuntary jitter is observed (faccification).
SMA Jokebe	autosomal dominant	Amazed in adult prox. and distal m - tsy.
SMA (type LED1)	autosomal dominant	Atrophy of the lower limbs in newborns.
SMA type RMA	autosomal - recessive	Atrophy of the distal muscles with impaired innervation and epileptic seizures
SMA with congenital bone fractures	autosomal - recessive	Heavy symptoms, as in case of illness. Verdnig-Hoffman, burdened by fractures.
SMA with hypoplasia	autosomal dominant	Congenital abnormal brain with cerebral symptoms, microcephalus and development delay.
SMA juvenile asymmetric type	--------------	Her young Indian men sick

This table should pay attention to the last two types of spinal amyotrophy:

• Sumy with hypoplasia is accompanied by deviations of mental and mental development, which is not typical for the rest of the disease.
• Asymmetric juvenile (Indian) amiotrophy is inherited. At the same time, the disease after two to five years of sluggish flow can stabilize. Symptoms of fasciculation with this specific form are rarely observed.

Treatment of spinal amiotrophy

Cure such a kind of disease, as well as any hereditary pathology affecting the dorsal or brain, is radically impossible. The effectiveness of many drugs used today during amyotrophy therapy has not been proven. The essence of treatment is reduced to an increase in the protein participating in the formation of SMN motor neurons.

Ways to treat SMA

So, the following drugs are mainly applied:

• valproic acid;
• oxybutirate sodium;
• nosinsen (new medicine introduced in the USA in 2016 for the treatment of SMA).

Supporting treatment (IFC, massage, physiotherapy) is also needed, a special protein diet at which possible contraindications are taken into account. Patients, devoid of independent movement, need social care.

Spinal muscle atrophy (SMA) is a rare neuromuscular disease characterized by the loss of lower motor neurons and the progressive exhaustion of muscles, often leading to early death.

Spinal amyotrophy have a wide range of gravity, manifesting in both babies and adults. The most commonly used classification looks like this:

A type	Name	Age of detection	Characteristic
SMA1	Verdnig-Hoffman disease	0-6 months	The hard form is manifested in the first months of life, as a rule, with a rapid and unexpected start ("flexible child syndrome"). The fast death of motor neurons causes a decrease in the function of the basic organs of the body, especially the respiratory system, and the respiratory failure caused by pneumonia is the most common cause of death. If children with a diagnosis of spinal amiotrophy of type 1 are not placed on artificial ventilation of the lungs, they, as a rule, do not live up to a two-year-old age, while death occurs within a few weeks in the most difficult cases (sometimes it is called SMA type 0). It is known that with proper respiratory support patients with easier years of type I, which accounts for about 10% of cases, wait to adolescent or even adult age.
SMA2.	Disease Dubovitsa	6-18 months	Intermediate shape is striking children. Unfortunately, they will not be able to walk or stand, but keeping the situation sitting at least some of the life is possible. The onset of weakness is usually marked 6-18 months after birth. Progression is greatly different, some children gradually become weaker, while others thanks to careful care longer faced problems. These children may have its correction using orthopedic devices to help breathing. The muscles of the body are weakened, which leads to serious problems with breathing. The life expectancy is reduced, but most people who have a spinal amyotrophy of type 2 wait to mature age.
SMA3	Kugelberg-Vallangera	12 months and more	Juvenile spinal amyotrophia usually manifests itself in children older than a year. They can walk without support for some time, although many later lose this ability. The involvement of the respiratory system into the disease is minimal, and the life expectancy is normal or almost normal.
SMA4	—	Only adults	Adult shape (sometimes classified as SMA3 with late beginnings) is usually manifested after the third decade of life with a gradual weakening of the muscles - basically affects the proximal muscles of the limbs. In this regard, often patients are forced to move on a wheelchair. Other complications are rare, and the life expectancy does not change.

The most severe form of spinal atrophy of type I is sometimes called a motel type 0 (or severe children's form) and is diagnosed in children who were born so weak that could live only a few weeks even with intensive respiratory support. Sumy type 0 should not be confused with SMARD (spinal muscle atrophy with respiratory distress), which can be very similar symptoms and a course, but the genetic cause differs from spinal-muscular atrophy.

Motor development in people who have spinal amyotrophy is usually evaluated using proven functional scales - Chop Intend (developed in Philadelphia), or a motor measurement scale, or one of several variants of the Hammersmith scale.

The reasons

Spinal muscle atrophy is associated with genetic mutation in the SMN1 gene.

The human chromosome 5 contains two almost identical genes at the 5Q13 location: a telecommormal copy of SMN1 and a centromedinal copy of SMN2. In healthy people, the SMN1 gene encodes a protein of motor neurons, which, as follows from his name, plays a decisive role in the survival of these cells.

In people affected by the SMN1, the SMN1 is mutated in such a way that it cannot properly encode SMN protein - this is due to the "cutting" of some encoding fragments, or due to other point mutations (often leading to the SMN2 functional conversion). However, almost all people have at least one functional copy of the SMN2 gene (most of which have 2-4 of them), which still encodes small amounts of SMN protein - about 10-20% of the normal level. That is why some neurons still survive.

However, in the long run, the reduction in the availability of SMN protein leads to the gradual death of the motor neurons cells in the front rog of the spinal cord and in the brain. The muscles that depend on these motor neurons have reduced innervation (also called denervation) and, therefore, much less control from the CNS.

Reducing the transfer of pulse through motor neurons leads to a decrease in the contractile activity of the denervized muscle. Consequently, the denervated muscles undergo progressive atrophy due to the lack of their involvement in motion.

The muscles of the lower extremities are usually amazed first, they follow the muscles of the upper extremities, spine and neck, and in more severe cases - pulmonary and chewing muscles.

The seriousness of the symptoms of the disease is generally related to how well the remaining SMN2 genes can compensate for the loss of the SMN1 function. This is partly associated with the number of copies of the SMN2 gene, present in the chromosome. While healthy people carry two copies of the SMN2 gene, in people with SMA can from 1 to 4 copies of the gene, and the more the number of copies of SMN2, the less pronounced disease. Thus, most children with SMA type I have one or two copies of SMN2; People with SMI II and III usually have at least three copies of SMN2; And people with SMI IV usually have at least four copies. However, the correlation between the seriousness of symptoms and the number of copies of SMN2 is not absolute, and it seems there are other factors affecting the severity of the disease.

Spinal muscle atrophy is inherited by autosomal-recessive type. This means that the defective gene is on an outosome (incomplete chromosome). Two copies of a defective gene (one from each parent) are necessary for the inheritance of the disorder: parents can be carriers and not have signs of the disease. Due to mutations without apparent inheritance from parents, the disease appears only in 2-4% of cases.

The spinal amyotrophy is striking people of all ethnic groups. The overall prevalence of SMA all types is in the range of 1 per 10,000 people; The gene frequency is about 1: 100, so about one of 50 people is a carrier.

Sick brothers and sisters usually have a very similar form of the disease. Nevertheless, there are different types of SMA among brothers and sisters, which is a rarity.

Signs and symptoms

Symptoms vary depending on the type of SMA, the stage of the disease, as well as individual characteristics. The signs and symptoms below are most often found if the patient has a spinal amiotrophy type 0 or 1:

• Areflexia, especially in the limbs
• General, low muscle tone, lethargy;
• Difficulties with walking, supporting position standing or sitting;
• In young children: the adoption of the position of the frog paws in the sitting position (hips are allocated, the knees are bent);
• Loss of the strength of the respiratory muscles: a weak cough, a weak cry (in babies), accumulation of secretion in the lungs or throat, respiratory failure;
• A bell-shaped torso (caused by the use of abdominal muscles for breathing) with a severe type ofma;
• Facciculation (twitching) language;
• Difficulties with sucking and swallowing, chewing.

Diagnostation

The most severe manifestations of spinal amyotrophy occur even before birth. They are noticeable for mothers in late pregnancy, reduced or missing fetal movements. Symptoms are critical (including respiratory distress and poor trophy), which usually lead to death for several weeks after birth, unlike the easiest adult form, in which muscle weakness can manifest itself after decades and progress for years, in general, without reducing life expectancy .

After birth, the symptoms that indicate the need for genetic analysis are:

• Progressive bilateral muscle weakness with the preceding asymptomatic period;
• Floating the wall of the chest when inhaling and protruding the abdomen;
• Hypotension associated with the absence of reflexes.

While the above-mentioned symptoms only indicate the disease, the diagnosis of SMI can be confirmed with absolute confidence only with the help of genetic testing. The study is usually carried out using a blood sample.

Pre-implantation genetic diagnostics is used for screening affected mothers of embryos during an extracorporeal fertilization.

Prenatal testing on mothers is possible by sampling samples of chorion vault, cellile analysis of the fetus DNA and other methods. Such a study is conducted in case the doctor suspects the fetus this pathology and wants to confirm the diagnosis. If it is confirmed, it may be an indication for the abortion of pregnancy.

Those who risk being media are a defective gene, it is advisable to make an analysis during the family planning, as such people are not sick, risk having sick children. An indication of such a necessity is primarily cases of Mis for the nearest relatives.

An experimental study method is screening in newborns, which, according to doctors, should confirm the presence of a disease in the child in the early stages. This gives certain goal doctors in order to start a possible therapy. There is still no convincing evidence of the effectiveness of such screening.

Care and treatment

The clinical management of the patient with SMA varies depending on gravity and type. Treatment of individual patients with the same type of disease may vary. With the most severe forms (types 0/1), people have the greatest muscle weakness requiring immediate intervention. With light shapes that manifest themselves in adulthood, patients may not seek help.

Respiratory care

The defeat of the respiratory system is the most common cause of the death of patients with the first and second type of disease. Type 3 spinal amyotrophy can give similar symptoms, but very rarely. Complications arise due to the fact that the innervation of intercostal muscles is stopped, which are important participants in the respiratory process. The diaphragm is amazed less.

After weakening the nervous regulation, the muscles never completely restore the functional ability to participate in the act of breathing, as before. Thus, breathing presents difficulties, the risk of lack of oxygen, surface respiration and insufficient purification of respiratory tract arises. These problems most often arise during sleep when the muscles are most relaxed. Weakness of swallowing muscles, combined with the inability to fully cough leads to aspiration of small particles, and then pneumonia.

To help in breathing, non-invasive ventilation, tracheostomy can sometimes be carried out in more severe cases; Both ventilation methods extend the survival in equally.

The removal of sputum of the respiratory tract is made manually (with special equipment), physiotherapy is assigned.

Food

The heavier the course of the disease, the greater the likelihood of health-related health problems. They include difficulties with feeding, chewing and swallowing, the inability to close the mouth. People with such difficulties may be subject to increased risk of overeating or malnutrition.

Other difficulties, especially in patients with severe forms of the disease, include gastric obstruction, gastric reflux, constipation, vomiting, and bloating. In this regard, it may be necessary to have a feeding tube or gastroity.

In addition, metabolic disorders arising from spinal muscle atrophy, worsen the β-oxidation of fatty acids in the muscles and can lead to organic acdemia and subsequent destruction of the muscles, especially when fasting.

Doctors recommend patients who have spinal amyotrophy, with progressive symptomatics to use products with low fat content, prefer more liquid product consistency (it helps to avoid aspiration) and eat frequently small portions.

Orthopedic care

Problems with a skeleton associated with weak muscles in motion include "Tugness" of the joints with a limited range of movements, hip dislocations, spinal deformation, osteopyation, increased risk of fractures and pain. The weakness of the muscles, which usually stabilize the joints in the spine, leads to and (or) scoliosis, joint contractures. The posture is of great importance in the development of complications, as well as the position on the bed or in a wheelchair. People with SMOs can also extract much benefit from various forms of physiotherapy, employment therapy, leaps with a coach.

Mobility support

Orthopedic devices can be used to support the body and to facilitate walking. For example, orthopedic devices, such as AFO (orthoses of the ankle joint), are used to stabilize the foot and to facilitate gait, TLSO (breast lumbar sacral orthosis) is used to stabilize the body.

Medicia treatment

Nusinersen (SpinRaZa) is the only approved drugs for the treatment of muscle atrophy of the spine. It is introduced directly into the central nervous system using intrathecal injection. The drug was approved by the European Commission in a centralized manner in June 2017.

Nusinersen modulates alternative SMN2 gene splasing, turning it to the SMN1 gene, thereby increasing the SMN protein level in the CNS. The drug applies to CNS and peripheral tissues. The main way of removal is likely to be selected with the urine nosylinsen and its metabolites.

Forecast

The absence of pharmacological treatment of spinal muscle atrophy, over time leads to a rapid deterioration of patients. Survival increased in patients with heavy motals with active supportive respiratory and food support.

Most children with a diagnosis of SMA type 0 do not reach the age of 4, with the cause of death acts respiratory failure. Long-term survival with SMA type I type is not sufficiently proven, nevertheless, the latest achievements in respiratory support made it possible to extend the life with such patients.

With SMI II type, the disease progresses slower, but the life expectancy is less than that of a healthy population. Mortality up to 20 years is frequent, although patients with SMO second type become parents, they will be seized with grandchildren.

Sumy Type III allows you to have a normal life expectancy subject to medical care standards. Type IV occurring in adults means only a reduction in mobility and does not affect the life expectancy.

Spinal muscular atrophy is the main genetic The cause of death in childhood. Let's figure out for the causes and ways to change the life of a child, and also learn what treatment methods are available today.

What is spinal muscular atrophy

Spinal muscular atrophy (SMA: Spinal Muscular ATROPHY) - This is a neuromuscular disease of an autosomal-recessive type, characterized by the death of motor neurons located in the front rog of the gray substance of the spinal cord and at the bottom of the brain stem.

Motor neurons - these are cells from which the nerves are formed, intended for controlling skeletal and cross-striped throats and larynx muscles: when they degenerate, whole groups of fibers are exposed to Atrophy And, accordingly, the result is muscular weakness.

The operations of the eye muscles, although controlled by the motor neurons of the encefial brain trunk, is not disturbed in this disease.

Frequency spinal muscular atrophy ranges from 1: 6000 to 1: 10,000, and all ethnic groups are subject to it; It is a rare disease, is one of the most common neuromuscular diseases, more precisely after dystrophy Duzhenna.

Cause of spinal muscular atrophy

Cause of spinal muscular atrophy It was discovered in the mid-90s, a hundred years after the first description of the disease. In 95% of cases, we are talking about deletion in the gene SMN1, localized on the long shoulder chromosome 5 (deletion is the loss of DNA sequence).

Since the spinal muscle atrophy is inherited by autosomal-recessive type, a person should receive both copies of the bad SMN1 - from the mother and from his father. Such parents are called heterozygous or carriers, and they do not have symptoms of the disease. Media are found with a frequency of 1:50.

The SMN1 gene encodes the SMN protein, which is used in the cytoplasm and the kernel of all cells and is crucial for the formation of SNRNP, small nuclear ribonucleoproteins, components splicing machines.

Why is the omnipresent SMN protein is critical factor To survive and properly functioning motor neurons?

Other hypothesis were formulated to explain the anti-apoptic role SMN:

• the need for this protein is higher in motor neurons than in other tissues.
• according to other authors, this can be explained by the fact that SMN protein is involved in transportation along axons of RNA-binding proteins.

Despite all the assumptions, it is currently still unclear which of many functions of SMN protein is associated with the development of spinal muscle atrophy.

4 types of spinal muscular atrophy

Spinal muscular atrophy classified by four types according to:

• with age The appearance of symptoms
• with maximum motor activitywhich is capable of patient

25% of persons avoid accurate classification. In addition, people suffering from one type of disease, symptoms can differ significantly.

1 Type - Verdnig-Hoffman disease

This is the hardest form of spinal muscle atrophy, is 50% of all cases.

Its main features:

• manifest until the 6th month of life
• the child has poor and dery muscle mass: He moves little, because it can not resist the power of gravity, unable to keep her head in a vertical position and sit without support
• bones are fragile and susceptible to fracturesIn addition, scoliosis develops in the spine. Problems with bones in a patient with spinal muscle atrophy do not surprise, since it is the physical activity that contributes to the mineralization of bones
• reflex sucking and swallowing is weakso such a child is hard to feed
• baby chest less than normal Due to the weakness of the respiratory muscles. Cash reflex is weak, which disrupts the process of getting rid of the secretions (mucus and solid particles, including microbes)

In children suffering from spinal muscular atrophy of 1 type, pneumonia often develops, as they are not able to get rid of any pathogenic microorganisms with a cough, as well as due to loss of control of swallowing muscles, which cannot prevent saliva and slices of food In the lungs. Repeating pneumonia lead, unfortunately, to respiratory failure.

For those who suffer from this form of pathology the forecast is unfavorable: death comes within 2 yearsEven the best treatment extends only to 5 years.

2 Type - Dube Dube

Intermediate form of spinal muscular atrophy.

Let's see the characteristics:

• manifests between 6 and 18 months
• child shows motoric Delay Delay: Unable to sit, he needs support to stand, and will never learn to walk. May have a light tremor hand
• at the same time, the type also notes a tendency to development. scoliosis and fragility of bones
• some small patients dysphagia becomes an obstacle to absorb sufficient for the development of calories
• cash reflex can relax, facilitating the appearance respiratory infections

When spinal muscular atrophy of type 2, also high risk of development respiratory failure. The progression of symptoms is so diverse that some patients die in infancy, others are able to achieve maturity.

3 Type - Kugelberg-Vanther's disease

Children's form of spinal muscle atrophy, which:

• may arise from the age of one and a half years
• compared to previous cases, children can stand and walk on their own, this ability in some cases persists to mature age
• observed tremor hands and problems with joints and scoliosis
• breath and swallowing disorders manifest less often than at 1 and 2 types

In people suffering from 3 types of spinal muscular atrophy, the average life expectancy is comparable to healthy people.. But due to nutritional problems and low physical activity, often have overweight.

4 Type of spinal muscular atrophy

This is an "adult" form of spinal muscular atrophy, a softer and less common disease. Usually occurs after 35 years and slowly progresses, affecting, in particular, the ability to move. May appear savoruds and breathing problems.

Life expectancy is normal.

How to recognize spinal muscle atrophy

Specialist in children's neurology We will ask a number of questions to get a detailed report on the medical history of the child and his family, after the procedure physical examinationTo assess the physical condition of the small patient.

Confirmation of the diagnosis of spinal muscular atrophy is achieved due to genetic test: Take a blood sample and is investigated for the presence of an abnormal SMN1 gene. The test can be used to find media.

The search for a faulty SMN1 can also be carried out by biopsy Village Chorionwhich are part of the placenta, which makes it possible to prenatal diagnostics in the case of:

• if the couple had already a child affected by spinal muscular atrophy
• partners are found that they are carriers, but still though to give birth to a child

Sometimes it happens that it is impossible to accurately say that this is a spinal muscular atrophy. Then use other teststhat help carry out a differential diagnosis between spinal atrophy and other pathologies of nerves and muscles:

• electromyiographywhich measures the electrical activity of muscles
• muscular biopsy, that is, the study of muscle fabric samples
• evaluation of the concentration of Creatine Kinase, enzyme the level of which rises when muscles damage

How to facilitate the symptoms of spinal atrophy

At the moment there are no drugs for the treatment of spinal muscular atrophy, so patients can only take advantage of supporting treatment.

Supporting therapy

Basic on three "cornerstone":

• dietology
• breath

For patients of school age, it is important that they actively participate in school events, because their physical disabilities do not affect the ability to learn.

Physiotherapy

Physiotherapy is necessary regardless of the age of a person. Exercises will allow maximizing the amplitude of movements to prevent or slow down the loss of shallow motility. Children with spinal muscle atrophy of 1 and 2 types get tremendous benefits from gymnastics in the pool, as water helps stimulate all muscle mass.

Patients with 3 types of spinal muscle atrophy are needed orthopedic devices (wheelchairs, parapes, etc.), which provide convenience and mobility. Exercises are also important because they help prevent scoliosis, which aggravates problems with breathing and movements.

Dietology

Each person suffering from spinal muscular atrophy must have its own individual power plan to prevent insufficient or redundant power.

For those children who have great difficulties in breast feeding, chewing and swallowing, you need to take action to avoid such complications as aspiration pneumonia.

• You can resort to the use of a nasogastric probe that passes through the nose and delivers food into the stomach. It is relatively easy to install and remove, but it can proceed, then it should be replaced
• Another option is gastrostomy, that is, the output of the tube from the stomach; It is easier to maintain, but the procedure is performed in the operating room under anesthesia.

Breath

In this case, there are three goals for with spinal muscular atrophy:

• patients and all people who come into contact with them must be vaccinated, for example, against influenza virus, pneumococcal infection and cougteries of pertussis, because respiratory tract infection can be very dangerous for such patients
• if the cough reflex is weak, it can be corrected using a special device (Cough Assist): it creates a rapid pressure change outside and inside the lungs, and the rapid passage of air in respiratory tract, which mimics cough, freeing the airways from the secret and microbes
• finally, an assessment of the respiratory function of these subjects according to the degree of saturation oxygen in the blood is important. If the amount of oxygen is less needs, it is more serious to consider the idea of \u200b\u200busing a mechanical respirator. Initially, it is used in case of respiratory infections and during sleep; With the development of the arrhyfoia - all day.

Possible therapeutic strategies

Opening the cause of the disease discovered for research groups a large direction for search treatment methods aimed at the maximum possible slowdown in the progression of symptoms: Improving the level of SMN protein.

• Since spinal muscle atrophy is a monogenic disease, it allows to intervene in the root of the ailment, providing patients with the functioning gene SMN1 (gene therapy)
• In persons suffering from spinal atrophy, but having a gene SMN2, it is possible to increase the expression of this gene and block the exception of exon 7 during the splicing immature mRNA.

In both cases, the amount of SMN functioning protein increases.

AVXS-101. - An experimental drug developed by the Biotechnology company Aveksis, who managed to reach the 1st stage of experiments in humans, in assessing the safety of treatment, and it starts checking efficiency.

Avexis focused on children suffering from type-type spinal muscular atrophy, because it is the most common and deadly type of disease.

AVXS-101. Consists of a large number of particles of the adeno-associated virus of serotype 9, incapable of replication, but containing one copy of the normal SMN1 gene.

It is introduced into the body intravenously, able to overcome the hematorecephalic barrier and achieve motor neurons.

DNA molecule, transferred by each viral vector, is made in the laboratory. It does not change the DNA of the patient; Contains promoter, i.e. The sequence that promotes DNA transcription in RNA and guarantees constant production of SMN protein.

• AVXS-101 is well tolerated by small patients with type 1 atrophy
• no child experienced "events": an event is the death or use of a mechanical respirator for 16 hours every day for 2 weeks in a row not related to acute respiratory infection.
• improving motor skills
• 100% of patients who did not have difficulty feeding remained stable
• 8 out of 10 children who entered the study without breathing, still do not need support