What Is SMA (Spinal Muscular Atrophy)?

What Is SMA?

Spinal muscular atrophy, or SMA for short, is a genetic, that is, hereditary, motor neuron disease that affects the central nervous system, the peripheral nervous system and the voluntary muscle movements of the skeletal muscle system. There are approved treatments for SMA. SMA occurs in about 1 in 10,000 births; about 1 in 40–50 people in the population is a carrier. Carrier screening for SMA is recommended for couples planning a pregnancy, preferably before pregnancy.

SMA is not a muscular dystrophy but a motor neuron disease: the lower motor neurons are lost, and the muscles, no longer receiving nerve signals, waste away neurogenically. 

Most of the nerve cells that control the muscles in the body are located in the spinal cord. In SMA, the muscles in the body cannot receive signals from the nervous system and cannot respond to them. When muscles are not stimulated regularly by nerve cells, they undergo atrophy, that is, they begin to shrink.

In SMA, loss of nerve cells called motor neurons is observed in the spinal cord. In SMA, the muscles closer to the center of the body, that is, the proximal muscles, are generally affected more than the muscles farther from the center, that is, the distal muscles.

What Causes SMA?

SMA is caused by a deficiency of a motor neuron protein called SMN, which is necessary for the survival of motor neurons in the nervous system. SMN plays an important role in gene expression in motor neurons.

This deficiency results from genetic defects in a gene called SMN1 on chromosome 5. The most common of these defects is the complete absence of the SMN1 gene. The neighboring SMN2 gene produces only small amounts of functional SMN protein and can only partly compensate.

Much more rarely, SMA can also be caused by mutations in genes other than SMN1, and these are called non-chromosome 5-related SMA.

What Are the Types of SMA?

The most common form of SMA is also called "chromosome 5 SMA or SMN-related SMA". It is divided into several different types, from 1 to 4, according to the age of onset of the symptoms of SMA, the rate of progression and the individual's ability to move.

Children who show the first symptoms at birth or in infancy have the lowest level of functioning. This is called type 1. SMA that begins in adolescents is classified as type 2 and type 3, while SMA that shows its symptoms in adulthood is classified as type 4. Under normal circumstances, the later SMA begins, the less motor function is affected.

In addition to the four types, there is also a type 0 form of SMA. SMA type 0 is characterized by reduced fetal movement in the last stages of pregnancy, and premature birth is commonly seen in this case.  In these newborns, severe weakness, hypotonia and heart defects are observed, and difficulty sucking, breathing and swallowing may occur.

The baby cannot reach the stage of righting itself. These babies usually have facial diplegia, that is, facial paralysis, a lack of response to environmental stimuli, and a congenital heart defect. Babies diagnosed with type 0 SMA mostly die within the first six months. 

Type 1 SMA is the most common type; symptoms begin within the first 6 months after birth. These children are usually very weak, have difficulty breathing, sucking and swallowing, and never reach the developmental milestone of sitting on their own. This is also called Werdnig-Hoffmann disease. In untreated type 1 patients, respiratory failure threatens life at an early age; drug treatments started early have markedly changed this course. 

The other name for type 2 SMA is Dubowitz disease. Type 2 SMA begins in babies who learn to sit without help at about 6 to 18 months of age but do not stand or walk on their own. Type 2 SMA accounts for about 30% of all SMA cases.

Muscle weakness is observed predominantly close to the center of the body and affects the lower limbs more than the upper limbs. However, the facial and eye muscles are generally not affected. Individuals with type 2 SMA can usually survive to adulthood, even though respiratory complications are a constant threat for them.

The symptoms of type 3 SMA generally appear between 18 months of age and adulthood. During these periods, affected individuals have acquired the ability to move independently. However, the progression of SMA can cause difficulty falling and climbing stairs due to proximal weakness. Some individuals affected by this type gradually lose the ability to stand and walk during adolescence, and a need to use a wheelchair for mobility arises.

In other cases, the ability to walk may never be lost. In most cases of these types, foot deformities and scoliosis develop. In type 3, life expectancy is generally normal and marked respiratory muscle weakness does not usually develop. This type is also called Kugelberg-Welander disease.

SMA that appears at the end of adolescence or in adulthood, type 4 SMA , is called late-onset SMA. This type has no average effect on an individual's lifespan. Patients can reach all stages of motor development and can commonly keep their mobility throughout life. 

What Are the Complications That Can Occur with SMA?

The foremost of the complications that SMA can cause is loss of control over the muscles. Accordingly, the most important complication of the disease is that the muscles that control breathing begin to lose their function.

Weakness of the respiratory muscles means that air cannot move in and out of the lungs well. Inadequate breathing, in turn, has negative effects on general health. Signs of weakening of the respiratory muscles include headaches, difficulty sleeping at night and insomnia, frequent yawning during the day, excessive sleepiness throughout the day, poor concentration, difficulty lying flat, chest infections and, ultimately, heart damage and respiratory failure.

The individual should pay attention to respiratory function throughout life and should take particular care with infections. At this stage, the doctor will help the individual by providing the medical support needed to clear secretions caused by infections. 

The legs tend to show weakness before the arms. The hands are generally the limbs that stay strong the longest, and even when they weaken, they usually remain strong enough to use a computer keyboard. 

Scoliosis , that is, curvature of the spine is also a common problem in SMA and requires medical intervention. Scoliosis occurs because of weakness of the muscles that support the spine, which is normally a flexible column, and it can be very uncomfortable for the individual.

Scoliosis can directly interfere with posture and the ability to move. It can harm the individual's body shape and appearance. In cases where the spinal curvature is very severe, difficulties in breathing healthily may again arise.

Individuals with SMA usually begin to show a scoliotic curve early in life. This curve is generally treated with bracing until the child reaches an age suitable for surgery. In many cases, growth must be completed before the spine is surgically corrected and fused. Early surgical intervention can be considered only when the child's respiratory function is impaired. 

Some types of SMA are not due to chromosome 5 or SMN deficiency. The severity of these types and which muscles they affect vary greatly from case to case. The most affected muscles also vary greatly. While most forms, like the chromosome 5-related form, mostly affect the proximal muscles, there are other forms that mostly affect the distal muscles, which are farther from the center of the body, at least initially.

What Are the Symptoms of SMA?

The symptoms of SMA cover a wide range depending on the type and severity of the disease. The most obvious sign and symptom of SMA is weakness in the voluntary muscles. The muscles most affected by this disease are those closest to the center of the body, such as the shoulder, hip, thigh and upper back muscles. If the back muscles weaken, spinal curves or a hunched back may develop.

The lower limbs generally appear to be more affected than the upper limbs, and a decrease in tendon reflexes is observed.

In cases where the muscles used for breathing and swallowing are affected by SMA, specific complications that cause abnormalities in these functions may occur. 

The age of onset and the level of motor function in SMA are related to how much usable protein is present in the 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 is not due to chromosome 5 or SMN deficiency, the severity of the disease and the affected muscles can vary greatly. Unlike the chromosome 5-related type, these may affect the distal muscles, which are farther from the center of the body, at least initially.

In chromosome 5-related SMA, the later the symptoms begin and the more SMN protein there is in the body, the milder the course of the disease.

In past years, onset of SMA in infancy indicated an average life expectancy of two years. However, medical experts today regard SMA as a process and believe that such predictions are not accurate. Nevertheless, SMA is the most common genetic cause of death in infants.

In infantile-onset types of SMA , the muscles between the affected baby's ribs are very weak, whereas the diaphragm is quite strong. For this reason, the child breathes mostly by moving the belly rather than the chest.

How Is SMA Diagnosed?

The first step in diagnosing any neuromuscular disease is usually a physical examination and learning the medical history of the patient's family. There are some simple tests used to distinguish spinal muscular atrophy from similar conditions such as muscular dystrophy.

Muscle weakness and hypotonia in infants are generally the first signs of SMA. Movement difficulties, loss of motor skills, proximal muscle weakness, hyporeflexia (absence of reflexes), involuntary twitching of the tongue and a low motor neuron count can help confirm the diagnosis.

To confirm the diagnosis of SMA , doctors may request a blood test for the presence of an enzyme called creatine kinase, or CK for short, in the weakened muscles. This does not give a definitive result because CK levels are elevated in many neuromuscular diseases.

A high blood CK level is not harmful in itself, but it indicates that muscle damage has occurred. In general, 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.

Doctors who strongly suspect SMA may consider a genetic test necessary, because this test is the least invasive and most accurate way to diagnose the presence of chromosome 5-related SMA, that is, type 1 - 4 SMA. Only a blood sample is taken for the genetic test. When SMA is suspected, the first and definitive diagnostic test is SMN1 gene analysis from blood; EMG and muscle biopsy are considered only if the genetic test is negative. 

In rare cases, doctors may request a muscle biopsy, usually from the thigh, in which a small sample of muscle tissue is taken and examined under a microscope.

Other tests used for SMA include a nerve conduction velocity test and electromyography, or EMG, which measures the electrical activity in the muscle. During the nerve conduction velocity test, the patient may feel sensations like mild electric shocks, and the EMG procedure requires short needles to be inserted into the muscles.

How Is SMA Treated?

There are approved treatments for SMA. However, medical experts continue their work toward a cure along various lines. The treatment process for SMA aims to manage the symptoms of the disease and keep its complications under control. 

Weakness of the respiratory muscles is a major problem in various forms of SMA. Although it is not the only cause, weakness of these muscles is the most common cause of death in type 1 and 2 SMA. Here, non-invasive ventilation can be provided through an oxygen mask or a mouthpiece. Today, the spread of portable and effective ventilators offers newborn SMA patients more options and greatly extends their lifespan.

Respiratory support can also help children and adults with different forms of SMA. In many cases, medical experts recommend starting with non-invasive ventilation methods first. This generally means delivering ambient air, not enriched with oxygen, to the person under pressure through a mask or mouthpiece. Such a system can come in many different forms and can be used at any time of day. It can also be removed easily for eating, drinking and talking.

When non-invasive ventilation is not sufficient, respiratory assistance can be provided with a tracheostomy, a method in which an opening is made in the trachea, that is, the windpipe. After this opening is made, pressurized air is delivered through a tube at the tracheostomy site. After an adjustment period, it is generally possible to eat, drink and speak normally with a tracheostomy tube.

Respiratory support treatment in SMA may also require clearing the secretions caused by breathing with a mechanical device, thereby preventing infections. The insufflator-exsufflator (cough assist) device used for this procedure is a type of device that can help clear secretions from the airway.

The device applies positive pressure to the airway and then quickly switches to negative pressure, mimicking a natural cough and clearing the inside of the airway. High-frequency chest wall oscillation devices also help clear the airway. This is a vest that rapidly inflates and deflates, thus mimicking normal breathing and, through the mini coughs it creates, moving secretions toward the larger airways.

Almost every individual suffering from SMA should get a flu shot every year to prevent respiratory tract infections. Other precautions include staying away from crowds, getting enough rest and eating healthily.

Weakness of the mouth and throat muscles can cause swallowing problems. Those who have had SMA since infancy in particular may have difficulty swallowing and sucking. Weak sucking leads to dehydration, that is, loss of body fluid, and inadequate nutrition, while difficulty swallowing can lead to airway obstruction and infections caused by inhaled foods or liquids. 

Babies with severe swallowing and sucking weakness can often be fed by alternative methods such as a feeding tube called a gastrostomy tube, or G-tube. A feeding tube is a small, flexible tube that allows liquid food to bypass the mouth, throat and esophagus and reach the stomach directly.

Some feeding tube systems are designed so that they can be detached from an opening on the abdomen when not in use. In some cases, G-tube users can be fed both through the tube and normally by mouth. 

Speech-language pathologists are trained to treat speech-related problems as well as swallowing problems. These specialists can advise the individual on coping with weakness of the swallowing muscles, preparing appropriate food and using gastrostomy tubes. 

Some medical experts believe that in some cases severe spinal curvatures can compress the lungs and endanger respiratory function. To prevent this, a back brace or corset that supports a child with SMA in a certain position may be prescribed to try to guide 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 for spinal curvature is almost always spinal straightening surgery. This surgery can be performed if the individual's respiratory status is good enough to withstand surgery. The timing of back surgery is important. Doctors generally prefer to wait until the growth of the spine is complete, because this allows simpler surgical techniques to be used. However, if the individual's respiratory status is worsening, surgical intervention can be performed earlier. 

Special precautions must be taken for an individual with SMA who needs to undergo any surgery. Particularly in the early stages of SMA, muscle cells that do not receive nerve signals develop certain abnormalities as they try to "reach out" to nerves. These abnormalities can lead to dangerous reactions to the muscle relaxant drugs frequently used during surgery. Using different drugs can prevent this.

In the treatment of SMA there is nusinersen (Spinraza), an antisense drug that regulates the processing of SMN2 mRNA to increase the production of normal, functional SMN protein; it does not change DNA. Nusinersen can be used at all ages. Approved treatments that change the course of the disease are available for SMA: nusinersen, risdiplam and onasemnogene. The best results are obtained when treatment is started before symptoms appear. 

Living with SMA and Home Care

Individuals affected by SMA need good nutrition. However, there is very little evidence that any diet is beneficial against SMA. On the contrary, some diets can be harmful. Elemental diets based on special formulas made up of broken-down protein components, that is, amino acids, can cause problems for children with SMA , who naturally have little muscle tissue.

People with SMA are at risk of excessive weight gain, probably because they cannot exercise effectively and take in too many calories for their activity levels. Therefore, this weight should be kept under control under the guidance of a dietitian and a physician. In some cases, eating many small meals throughout the day may be more beneficial than three large meals a day. 

Adults with SMA can drive vehicles equipped with special hand controls. Many medical experts advise individuals with SMA that doing as much physical activity as is comfortable, without overdoing it, is a good idea for maintaining overall physical and psychological health and well-being. 

Protecting the joints from stiffness or injury, preventing loss of range of motion, that is, flexibility in the joints, and maintaining circulation are important for individuals with SMA. In addition, especially for children, it is important to allow and provide opportunities for enough movement to get around their surroundings.

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 assistive technology products can help even very young children explore the world despite weak muscles. Standing frames, walkers, various electric and manual wheelchairs and orthoses can help with standing or moving.

Information technologies, which are becoming increasingly widespread today, especially technological tools that can recognize voice commands, can help with writing, drawing, using a computer or phone, and electronically controlling environmental conditions such as temperature, lighting or television.