Spinal muscular atrophy, in short, SMA disease is a genetic, that is, hereditary motor neuron disease that affects the individual's central nervous system, peripheral nervous system and controlled muscle movements of the skeletal musculature. There is no definitive treatment for SMA disease. SMA disease is a very rare disease.
SMA is one of a group of diseases called muscular dystrophy characterized by symptoms of progressive weakness and loss of muscle mass. In many cases of muscular dystrophy, mutated abnormal genes interfere with the production of proteins necessary to build healthy muscle.
Most of the nerve cells that control the muscles in the body are found in the spinal cord. During the SMA process, the muscles in the body cannot receive signals from the nervous system and cannot react to them. When muscles are not regularly stimulated by nerve cells, they atrophy, that is, they begin to shrink.
In the process of SMA disease, losses are observed in nerve cells called motor neurons in the spinal cord. In SMA, the muscles closer to the center of the body, that is, the proximal muscles, are usually more affected than the muscles that are farther from the center, that is, the distal muscles.
Reasons
What Causes SMA Disease?
SMA is caused by a deficiency of a motor neuron protein called SMN, which is essential for motor neuron survival in the nervous system. SMN plays an important role in gene expression in motor neurons.
This deficiency is caused by genetic defects on chromosome 5 of a gene called SMN1. The most common of these defects is the absence of the SMN1 gene at all. The neighboring SMN2 gene is similar enough to do the job of this gene.
SMA disease can also be caused by mutations of genes other than the SMN1 gene, much more rarely, and they are called non-chromosome 5 origin SMA disease.
What are the Types of SMA Disease?
The most common SMA disease is also called “chromosome 5 SMA or SMN-associated SMA disease”. This SMA is divided into several different types, from 1 to 4, according to the age of onset of the symptoms of the disease, the rate of spread, and the mobility of the individual.
Children who exhibit the first symptoms at birth or in infancy show the lowest level of functioning. This is called type 1. While SMA disease that starts in young people is named as type 2 and type 3, SMA disease that shows symptoms in adulthood is classified as type 4. The later the onset of SMA disease under normal circumstances, the less affected motor function levels.
In addition to the four types, there is also the type 0 type of SMA disease. SMA type 0 is characterized by decreased fetal motility in late pregnancy, and preterm delivery is common in this condition. These newborns may present with severe weakness, hypotonia, and heart defects, while difficulty in sucking and breathing and swallowing.
The baby cannot reach the self-righting stage. Usually, these infants have facial diplegia, a lack of response to environmental stimuli, and a congenital heart defect. Babies diagnosed with type 0 SMA disease usually die within the first six months.
Significant symptoms of SMA disease occur between six months and one year after birth, indicating type 1 SMA disease. These children are often very frail, have difficulty breathing, sucking and swallowing, and never reach the sitting stage of developmental progress on their own. This is also called Werdnig-Hoffmann disease. Children with type 1 SMA may survive for several years with the help of mechanical ventilation and feeding tubes to assist with breathing and feeding.
The other name for type 2 SMA disease is Dubowitz disease. Type 2 SMA disease begins in infants who learn to sit unaided at about 3 to 15 months of age, but are unable to stand or walk on their own. Type 2 SMA disease accounts for approximately 20% of all SMA cases.
Muscle weakness is predominantly observed near the center of the body and affects the lower limbs more than the upper limbs. However, usually the facial and eye muscles are not affected. Individuals with type 2 SMA can usually live long enough to reach adulthood, even if respiratory complications are a constant threat to them.
Symptoms of type 3 SMA usually appear between 18 months of age and adulthood. During these periods, affected individuals gained the ability to act independently. However, progression of SMA disease may cause difficulty falling and climbing stairs due to proximal weakness. Some individuals affected by this type lose their ability to stand and walk over time, during adolescence, and the need to use a wheelchair for movement arises.
In other cases, the ability to walk may not be lost at all. Most cases of these types develop foot deformities, scoliosis, and respiratory muscle weakness. This type is also called Kugelberg-Welander disease.
Type 4 SMA disease that occurs at the end of adolescence or adulthood is called late-onset SMA. This type does not have an average effect on the lifespan of the individual. Patients can reach any stage of movement development and commonly maintain their ability to move for life.
What are the Complications that May Occur with SMA Disease?
One of the complications that SMA can cause is the loss of control over the muscles. Accordingly, the most important complication of the disease is the loss of function of the muscles that control respiration.
Weakness of the respiratory muscles means that air cannot get in and out of the lungs well. Insufficient breathing leads to adverse effects on general health. Symptoms of weakened respiratory muscles include headaches, difficulty sleeping and insomnia at night, frequent yawning during the day, excessive sleepiness during the day, poor concentration, difficulty lying flat, chest infections, and eventually heart damage and respiratory failure.
The individual should pay attention to respiratory functions throughout his life and pay special attention to infections. At this stage, the doctor will assist the individual in providing the necessary medical support to clear the secretions caused by infections.
The legs tend to show weakness before the arms. The hands, on the other hand, are usually the longest lasting limbs, and even when weakened, they usually remain strong enough to use a computer keyboard.
Scoliosis, or curvature of the spine, is also a common problem in SMA and requires medical attention. Scoliosis occurs due to weakness of the muscles that support the spine, which is normally a flexible column, and can be very uncomfortable for the individual.
Scoliosis can directly interfere with posture and mobility. It can harm an individual's body shape and appearance. In cases where the spinal curvature is very severe, difficulties may arise in performing healthy breathing.
Individuals with SMA usually begin to show a scolitic curve early in life. This curve is usually treated with support until the child is of age appropriate for surgery. In many cases, growth must be completed before the spine can be surgically straightened and fused. Early surgical intervention can be considered only in cases where the child's respiratory functions are impaired.
Some types of SMA disease are not due to chromosome 5 or SMN deficiency. The severity of these types and which muscles they affect varies greatly from case to case. vary greatly in the muscles most affected. While most forms, such as the chromosome 5 associated form, mostly affect the proximal muscles, there are other forms that mostly affect the distal muscles, at least initially more distant from the center of the body.
Symptoms
What are the Symptoms of SMA Disease?
The symptoms of SMA disease cover a wide spectrum, depending on the type and severity of the disease. The most prominent sign and symptom of SMA is weakness in controllable muscles. The muscles most affected by this disease are those closest to the center of the body, such as the shoulders, hips, thighs, and upper back. In case of weakening of the back muscles, spinal curves or humpback may develop.
The lower limbs usually appear to be more affected than the upper limbs, and tendon reflexes are reduced.
In cases where the muscles used for breathing and swallowing are affected by SMA, special complications may occur that cause abnormalities in these functions.
The age of onset of SMA and the level of motor function are related to how much usable protein is found in motor neurons. The senses of sight, hearing, taste, smell, and touch, as well as mental and emotional functioning, are completely normal in individuals with SMA.
If SMA disease is not due to chromosome 5 or SMN deficiency, the severity of the disease and the muscles affected can vary greatly. These may affect distal muscles that are further away from the center of the body, at least initially, as opposed to the chromosome 5 related type.
In SMA disease associated with chromosome 5, the later the symptoms begin and the more SMN proteins found in the body, the milder the course of the disease.
In the past years, the onset of SMA' disease in infancy indicated an average life expectancy of two years. However, today medical professionals consider SMA disease as a process and believe that such predictions are not correct. However, SMA is the most common genetic cause of death in infants.
In infantile-onset types of SMA disease, the muscles between the ribs of the affected infant are very weak, whereas the diaphragm muscle is quite strong. For this reason, the child often breathes by moving the belly rather than the chest.
Diagnostic Methods
How Is SMA Disease Diagnosed?
The first step in diagnosing any neuromuscular disease is usually a physical examination and obtaining the patient's family medical history. There are some simple tests used to differentiate spinal muscular atrophy from similar conditions such as muscular dystrophy.
Muscle weakness and hypotonia in infants are often the first signs of SMA disease. Movement difficulties, loss of motor skills, proximal muscle weakness, hyporeflexia (absence of reflexes), involuntary tongue twitches and low motor neuron count may help confirm the diagnosis.
Doctors may order a blood test for the presence of an enzyme called creatine kinase, or CK for short, in weakened muscles to confirm a diagnosis of SMA disease. This is inconclusive because CK levels are elevated in many neuromuscular diseases.
A high blood CK level is not harmful per se, but indicates that muscle damage has occurred. Generally, CK levels are normal in patients diagnosed with type 1 SMA, but slightly elevated in patients diagnosed with other types of SMA, such as types 2 and 3.
Physicians who strongly suspect SMA may consider genetic testing necessary, as it is the least invasive and most accurate way of diagnosing the presence of chromosome 5 associated SMA disease, ie type 1 to 4 SMA disease. Only one blood sample is taken for genetic testing.
In rare cases, doctors may order a muscle biopsy, usually from the thigh, to take a small sample of muscle tissue and examine it under a microscope.
Other tests used for SMA disease include the nerve signal conduction velocity test and tests called electromyography, or EMG, that measure electrical activity in the muscle. During the nerve conduction velocity test, the patient may feel sensations such as mild electric shocks, and during the EMG process, short needles must be inserted into the muscles.
Treatment Methods
How is SMA Disease Treated?
There is no known definitive treatment method for SMA Disease. However, medical professionals continue their studies from various branches for a treatment. The treatment process for SMA disease aims to manage the symptoms of the disease and to control the complications.
Weakness of the respiratory muscles is a major problem in various forms of SMA. While not the only cause, the most common cause of death in types 1 and 2 SMA is weakness of these muscles. Here, non-invasive breathing can be achieved through an oxygen mask or mouthpiece. Today, the prevalence of portable and effective ventilation devices provides more options for neonatal SMA patients and greatly extends their lifespan.
Respiratory support can also help children and adults with different forms of SMA disease. In many cases, medical professionals recommend starting with non-invasive ventilation methods first. This usually means that environmental and non-oxygen-enriched air is given to the individual in a pressurized manner through a mask or mouthpiece. Such a system can be found in many different forms and can be used at any time of the day. It can also be easily removed for eating, drinking and talking.
When noninvasive ventilation is not sufficient, respiratory assistance can be provided by tracheostomy, which is a method of opening a hole in the trachea, the windpipe. After this hole is opened, compressed air is given from a pipe in the tracheostomy area. It is usually possible to eat, drink and talk normally with the tracheostomy tube after the acclimatization period.
Respiratory support therapy in SMA disease may also require the removal of respiratory secretions with a mechanical device, thus preventing infections. The insufflator-respirator used for this process is a type of device that can help clear respiratory secretions from the airway.
The device applies positive pressure to the airway and then quickly returns to negative pressure, simulating a natural cough, and clears the inside of the tube. High-frequency chest wall oscillators also assist in clearing the airway. This is a vest that inflates rapidly, thus mimicking normal breathing and transmitting the secretions towards the larger airways thanks to the mini coughs it creates.
Almost every individual suffering from SMA should get a flu shot annually to prevent respiratory infections. Other measures to take include staying away from crowds, getting enough rest, and eating a healthy diet.
Weakness of the mouth and throat muscles can cause swallowing problems. Especially those who have had SMA disease since infancy may have difficulty swallowing and sucking. Poor sucking can lead to dehydration, i.e. thirst and malnutrition, while difficulty swallowing can lead to blockage of the airways and infections from inhaled food or fluids.
Babies with severe difficulty swallowing and sucking can be fed with alternative methods such as a feeding tube, often called a gastrostomy tube or g tube. A feeding tube is a small, flexible tube that allows liquid foods to bypass the mouth, throat, and esophagus and reach the stomach directly.
Some feeding tube systems are designed to be separated from an opening in the abdomen when not in use. In some cases, g-tube users can be fed both by tube and normally orally.
Speech-language pathologists are trained in the treatment of speech-related problems as well as swallowing problems. These specialists can advise the individual on coping with the weakness of the swallowing muscles, proper food preparation and the use of gastrostomy tubes.
Some medical professionals believe that in some cases, severe spinal curvatures can compress the lungs, compromising respiratory function. To avoid this, a back brace or brace can often be prescribed to support a child with SMA in a certain position to try to orient the spine as it grows. These supports do not solve the problem, but they can slow the progression of the curvature of the back.
The permanent solution to spinal curvature is almost always spine straightening surgery. This surgery can be performed if the respiratory condition of the individual is good enough to withstand the surgery. The timing of back surgery is important. Doctors often prefer to wait until the growth of the spine is complete, as this allows for simpler surgical methods to be used. However, if the respiratory condition of the individual is getting worse, surgical intervention can be performed earlier.
Special precautions need to be taken for an individual with SMA who needs to undergo any surgery. Especially in the early stages of SMA, muscle cells that do not receive nerve signals develop some abnormalities as they try to "reach" the nerves. These abnormalities can lead to dangerous reactions to muscle relaxants that are often used during surgery. Different drugs to be used can prevent this situation.
Spinraza, a new therapy that modifies the SMN2 gene, is available to increase the production of normal and functional SMN2 protein in the treatment process of SMA disease. Spinraza can be recommended for infants suffering from SMA, especially between the ages of 2 and 12. Apart from this, researches are continuing on treatments based on the delivery of missing genes for patients younger than 2 years old.
Living with SMA Disease and Home Care
Individuals affected by SMA need good nutrition. However, there is little evidence to suggest that any diet has any benefit against SMA. On the contrary, some diets can be harmful. Elemental diets based on special formulas made of broken protein components, namely amino acids, can cause problems for children with SMA who naturally have little muscle tissue.
SMA patients are at risk of gaining excess weight, possibly because they are unable to exercise effectively and consume too many calories for their activity level. Therefore, this weight should be kept under control under the guidance of a nutritionist and physician. In some cases, eating several small meals a day may be more beneficial than three large meals a day.
It is possible for adults with SMA to drive vehicles equipped with special hand controls. Many medical professionals recommend that it is a good idea to engage in physical activity as well as comfortable in moderation to maintain the overall physical and psychological health and well-being of individuals with SMA.
It is important for individuals with SMA to protect the joints from stiffness or injuries, to prevent the loss of range of motion, that is, to prevent loss of flexibility in the joints, and to preserve circulation. In addition, it is important, especially for children, to allow enough movement and opportunity to move around.
Exercising in a warm pool can be particularly beneficial for the individual. However, an individual with SMA should not swim alone and appropriate safety precautions should be taken.
Various technological support products can help even very young children explore the world despite weak muscles. Stands, walkers, a variety of electric and manual wheelchairs, and orthoses can assist with standing or moving.
Today, increasingly widespread information technologies, especially technological tools that can detect voice commands, can help to write, paint, use a computer or telephone, and electronically control environmental conditions such as temperature, lighting, or television.
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