Spinal Muscular Atrophy (SMA): Definition, Causes, Symptoms, and Treatment

SMA is a neurological disease that affects motor neurons.

SMA is a neurological disease that affects motor neurons, leading to muscle weakness and atrophy. When the disease begins to affect the respiratory muscles, it can result in life-threatening outcomes. Although a definitive cure is not yet possible, appropriate treatment can help halt the progression of the disease.

What is SMA?

Spinal muscular atrophy (SMA) refers to a group of genetic disorders that lead to muscle atrophy. SMA occurs due to the loss of nerve cells located in the brainstem and spinal cord. This loss causes dysfunction in the muscles innervated by these nerves, resulting in muscle atrophy. Due to the atrophied—or, in simpler terms, weakened—muscles, SMA patients may struggle with movements such as walking, standing, controlling head movements, swallowing, and breathing.

Some types of SMA are present from birth, while others manifest later in life. SMA is known to affect approximately one in every 8,000-10,000 people.

SMA is a progressive disease that leads to increasingly severe symptoms over time. Although there is currently no cure for SMA, available treatments can slow or halt the disease's progression. These treatments may also alleviate symptoms and improve the patient’s quality of life.

What Are the Types of SMA?

SMA has several types, categorized by the age at which symptoms appear, the patient’s life expectancy, and quality of life. The types of SMA are:

• SMA Type 1: Also known as Werdnig-Hoffmann disease, this type manifests within the first six months of life. Without early treatment, infants with SMA Type 1 may not survive past their first year. Symptoms can include muscle twitching, limited limb movement, and feeding difficulties. These patients generally lack the ability to sit, stand, or walk. However, newer treatment methods may enable these infants to gain sitting and walking abilities. SMA Type 1 can sometimes be diagnosed late in pregnancy when fetal movements decrease. The baby's movement difficulties become more evident within the first few months after birth.
• SMA Type 2: This type usually emerges when a baby is between 6 and 18 months old. Before the disease manifests, the baby may learn to sit. However, after onset, standing and walking become impossible, and untreated patients may even lose the ability to sit. Life expectancy for SMA Type 2 patients varies depending on the presence or absence of respiratory complications, and many can live into young adulthood.
• SMA Type 3: Also called Kugelberg-Welander disease, this type appears after 18 months of age. SMA Type 3 patients may experience joint problems, such as scoliosis and contractures, caused by muscle or tendon shortening. They retain significant abilities to sit and walk but struggle with activities like running, jumping, and climbing. Finger tremors may also be present. Additionally, these patients are at risk for severe respiratory infections. With proper treatment, SMA Type 3 patients can achieve a life expectancy close to that of a healthy individual.
• SMA Type 4: Also known as Adult-Onset SMA, this type emerges after age 21. Patients experience mild weakness, particularly in the proximal muscles near the trunk, though this weakness is generally not severe.

What Are the Symptoms of SMA?

The symptoms of SMA vary depending on the type of the disease and when it manifests.

Symptoms of SMA Type 1:

• Weakness and floppiness in the arms and legs (hypotonia)
• Weak, faint crying
• Difficulty with movement, swallowing, and breathing
• Trouble holding up the head or sitting without support

Symptoms of SMA Type 2 are generally milder than those of Type 1. They include:

• Difficulty standing up independently
• Weakness in the arms and legs
• Tremors in the hands and fingers
• Scoliosis (curvature of the spine in an S or C shape)
• Weakness in the respiratory muscles
• Difficulty coughing

SMA Type 3 patients can stand and walk independently, though they may lose these abilities over time. Additional symptoms include:

• Difficulty rising from a seated position
• Balance issues
• Challenges with climbing stairs and running
• Scoliosis

Symptoms of SMA Type 4:

• Weakness in the hands and feet
• Difficulty walking
• Muscle tremors and twitching

What Causes SMA?

SMA is caused by mutations in the SMN1 and SMN2 genes. These mutations lead to the inability of motor neurons in the spinal cord and brainstem to function properly.

Motor neurons are nerve cells responsible for controlling movement. The SMN1 and SMN2 genes are responsible for producing a protein essential for the function of motor neurons.

The SMN1 gene is primarily associated with the onset of SMA, while the SMN2 gene influences the severity and progression of the disease.

Genetic mutations that cause SMA are present in about 1 in every 40 to 60 people in the population. For a person to develop SMA, they must inherit mutated genes from both parents. However, even if both genes are inherited, the chance of developing the disease is 25%. Therefore, people with the genetic mutation can still live healthy lives.

How Is SMA Diagnosed?

SMA diagnosis often begins when families notice symptoms in their child. The doctor will carefully evaluate the child’s symptoms and take a detailed medical history of the child and family. Physical examination is crucial for diagnosis. If signs like muscle weakness or floppiness are detected, further tests may be required.

Blood tests, muscle biopsy, and electromyography (EMG) are some methods used in diagnosing SMA. EMG assesses muscle function and the nerve cells responsible for muscle movement.

If SMA is suspected during pregnancy, amniocentesis and chorionic villus sampling can confirm the diagnosis.

What Symptoms Accompany SMA?

People with SMA may have an increased susceptibility to respiratory infections. Pneumonia, particularly affecting the lower respiratory tract, can cause severe complications in these patients. Symptoms of pneumonia include coughing, fever, shortness of breath, wheezing, nausea, and vomiting.

Is There a Treatment for SMA?

While SMA cannot be completely cured, some recently developed treatments can help halt the disease's progression. SMA is a progressively worsening condition, but treatment can help prevent further deterioration and preserve abilities like sitting and walking.

New medications are available that focus on gene therapy to treat the disease. Alongside drug treatments, interventions to help SMA patients remain active can improve their quality of life. Breathing exercises, nutritional management, and activities to stretch and strengthen muscles can be beneficial. Assistive devices like ventilators and powered wheelchairs also support a better quality of life.

It is important for patients and their caregivers to be informed about SMA and to have supportive family and friends to improve adherence to treatment. SMA patients should seek care at a well-equipped medical center for both medical and supportive therapies.