Spinal Muscular Atrophy (SMA)

What is Spinal Muscular Atrophy (SMA)?

Spinal Muscular Atrophy (SMA) is a rare genetic disorder that affects the nerves controlling muscle movement. Imagine the brain sending a signal to your muscles, like a coach giving directions to a team. In someone with SMA, these signals struggle to reach the muscles because the motor neurons in the spinal cord responsible for transmitting those signals are damaged or missing.

This happens due to a defect in the SMN1 gene, which produces a vital protein that keeps motor neurons alive. Without enough of this protein, motor neurons deteriorate, leading to muscle weakness and shrinkage over time. As a result, activities such as crawling, walking, swallowing, or even breathing can become difficult.

SMA affects people of all ages and is one of the most common genetic causes of infant death. The severity and symptoms can vary widely depending on the type of SMA, with some individuals showing signs in infancy and others much later in life.

Spinal Muscular Atrophy Treatment

Types of Spinal Muscular Atrophy (SMA)

1. SMA Type 0 (Prenatal or Neonatal SMA)

SMA Type 0 is the rarest and most severe form, detected before birth or immediately after delivery.

• Onset: Before birth or at birth.
• Symptoms: Profound muscle weakness, poor movement, and breathing difficulties.
• Prognosis: Unfortunately, life expectancy is limited, with most infants not surviving beyond a few months.

2. SMA Type 1 (Werdnig-Hoffmann Disease)

SMA Type 1 appears within the first six months of life and is one of the most common forms.

• Onset: 0–6 months
• Symptoms: Severe muscle weakness, difficulty swallowing, and breathing issues
• Prognosis: Without treatment, life expectancy is often reduced, but recent therapies have significantly improved outcomes

3. SMA Type 2 (Intermediate SMA)

SMA Type 2 develops between 6 and 18 months of age.

• Onset: 6–18 months
• Symptoms: Children can sit but cannot stand or walk unaided; progressive muscle weakness
• Prognosis: Lifespan varies, but with therapy and medical care, individuals can live well into adulthood

4. SMA Type 3 (Kugelberg-Welander Disease)

SMA Type 3 typically manifests after 18 months and is milder compared to earlier-onset types.

• Onset: After 18 months to adolescence.
• Symptoms: Difficulty walking, frequent falls, or the need for mobility aids later in life.
• Prognosis: Most individuals have a near-normal life expectancy with ongoing physiotherapy and care.

5. SMA Type 4 (Adult-Onset SMA)

SMA Type 4 is the mildest form, appearing in early adulthood.

• Onset: 18 years or older.
• Symptoms: Gradual muscle weakness and fatigue, usually not affecting life expectancy.
• Prognosis: Slow progression and manageable symptoms through physiotherapy and lifestyle care.

Treatments for Spinal Muscular Atrophy (SMA)

1. Gene and Molecular Therapies

(a) Nusinersen (Spinraza®)

• How it works: Increases production of the SMN (survival motor neuron) protein essential for nerve and muscle function.
• Who it’s for: Approved for infants, children, and adults with SMA.
• Administration: Injected into the spinal fluid periodically.

(b) Onasemnogene Abeparvovec-xioi (Zolgensma®)

• How it works: Delivers a working copy of the SMN1 gene to replace the faulty one causing SMA.
• Who it’s for: Typically given as a one-time intravenous (IV) infusion to children under two years.
• Impact: Can dramatically improve survival and motor function in early-diagnosed patients.

(c) Risdiplam (Evrysdi®)

• How it works: Oral medication that boosts SMN protein production across the body.
• Who it’s for: Approved for patients aged two months and older.
• Benefit: Allows at-home treatment, improving accessibility and adherence.

2. Supportive and Rehabilitative Therapies (For All SMA Types)

• Physical Therapy: Helps maintain mobility, prevent joint contractures, and improve posture and balance.
• Occupational Therapy: Assists with daily living skills, adaptive tools, and independence in daily activities.
• Respiratory Therapy: Provides breathing support through non-invasive ventilation or airway clearance techniques, especially for severe types (Type 0–2).
• Nutritional Management: Ensures proper growth and energy levels, addressing feeding challenges or swallowing difficulties.
• Orthopaedic and Assistive Devices: Includes braces, standing frames, and wheelchairs to maintain movement and comfort.

3. Emotional & Social Support

SMA impacts not only patients but also their families. Emotional and social support resources such as counselling, support groups, and social services—help families cope, connect, and stay informed.

Spinal Muscular Atrophy Causes

1. Genetic Cause:

• Inherited Condition: SMA is a condition you are born with, meaning it’s passed down from your parents. 

• Genes Involved: Our bodies are made up of cells, and inside each cell are tiny structures called genes. Our bodies receive instructions on how to grow and function from genes. In SMA, a specific gene called the SMN1 gene doesn’t work properly.

• Role of the SMN1 Gene: The SMN1 gene makes a protein called the SMN protein. This protein is essential because it helps keep the nerve cells in the spinal cord healthy. These nerve cells send signals from the brain to the muscles, telling them to move.

• What Happens in SMA: The SMN1 gene is faulty or missing in people with SMA. Because of this, there isn’t enough SMN protein being made. Without enough of this protein, the nerve cells in the spinal cord start to die, and when these nerve cells die, the muscles don’t get the signals they need to move. Over time, this causes the muscles to become weak and shrink.

2. How It’s Inherited:

• Recessive Disorder: SMA is a “recessive” genetic disorder. This means that a child has to inherit two copies of the faulty SMN1 gene one from each parent to develop SMA.

• Carrier Parents: Sometimes, parents may carry one faulty SMN1 gene but don’t have SMA themselves because they also have one working SMN1 gene. These parents are called “carriers.” If both parents are carriers, there’s a 25% (1 in 4) possibility with each pregnancy that the child will inherit two faulty genes and have SMA.

3. Other Genes:

• SMN1 Gene: When the SMN1 gene is faulty, the body cannot produce enough SMN protein. This leads to the degeneration of motor neurons, resulting in progressive muscle weakness, reduced mobility, and other related complications.

• SMN2 gene: Another gene, called SMN2, also produces SMN protein, but it is less effective than SMN1. Some people with SMA have multiple copies of the SMN2 gene, which allows their bodies to generate more SMN protein. This typically results in milder symptoms and slower disease progression, making the number of SMN2 copies an important factor that doctors consider when assessing severity and planning treatment.

Spinal Muscular Atrophy Testing

1. Genetic Testing

Genetic testing is the main way to diagnose SMA.
A small blood sample is taken and checked for changes in the SMN1 gene, which makes the survival motor neuron (SMN) protein. If this gene is missing or faulty, it confirms SMA.

• Most SMA cases can be diagnosed with this test.
• It can also show whether someone is a carrier of the SMA gene.

2. Prenatal Testing

If there’s a family history of SMA, doctors can test a baby for SMA before birth. There are two common prenatal tests:

• Chorionic Villus Sampling (CVS): Done between the 11th and 14th week of pregnancy, this test takes a small sample of cells from the placenta to check for the SMA gene.
• Amniocentesis: Usually done between the 15th and 20th week, it tests a small sample of the amniotic fluid (the fluid around the baby) for SMN1 gene changes.

These tests help parents prepare and discuss treatment options early.

3. Newborn Screening

In some places, SMA is included in newborn screening programs.
A few drops of blood are taken from the baby’s heel soon after birth to test for SMN1 gene mutations. Detecting SMA early allows treatment to begin before symptoms start, improving long-term outcomes.

4. Carrier Screening

Carrier screening is a simple blood test that helps adults find out if they carry the SMA gene mutation.

• It’s recommended for people with a family history of SMA or couples planning to have children.
• If both parents are carriers, there’s a chance their child could inherit SMA.

Carrier testing helps families make informed decisions about pregnancy and genetic counseling.

5. Additional Tests

Sometimes, doctors may suggest other tests to check muscle and nerve health, especially if SMA is suspected but not confirmed:

• Electromyography (EMG): Measures electrical activity in the muscles.
• Muscle Biopsy: Examines a small piece of muscle under a microscope.
• Nerve Conduction Velocity (NCV) Test: Checks how quickly signals travel from nerves to muscles.

These tests give doctors more details about muscle weakness and nerve function.

Why Early SMA Testing Is Important

Early SMA diagnosis makes a big difference. With new gene therapies and SMA medications, starting treatment early—sometimes before symptoms appear—can greatly improve muscle strength and quality of life.

Spinal Muscular Atrophy Life Expectancy

Spinal Muscular Atrophy (SMA) life expectancy varies by type, age of onset, and access to treatment. The five main types being SMA Type 0, Type 1, Type 2, Type 3, and Type 4 differ in severity and long-term outlook.

(a) SMA Type 0 and Type 1: Severe Forms

Type 0 SMA appears before birth and is the most severe, causing profound weakness and breathing failure. Sadly, life expectancy is usually just a few months.
Type 1 SMA (Werdnig-Hoffmann disease) develops within the first six months of life. Without treatment, most children did not live beyond two years. However, new therapies like Zolgensma, Spinraza, and Evrysdi have dramatically improved survival and motor function.

(b) SMA Type 2: Intermediate Form

Type 2 SMA appears between 6–18 months. Children can sit but often need help to move or walk. With early intervention, supportive care, and modern SMA treatments, many now live into their 30s or longer with improved quality of life.

(c) SMA Type 3 and Type 4: Mild Forms

Type 3 (Kugelberg-Welander) and Type 4 (adult-onset) SMA progress slowly and usually do not affect life expectancy. People may experience mobility issues but can lead normal, active lives with physical therapy and supportive care.

Improved Outlook with Modern Treatments

Advances in gene therapy (Zolgensma) and medications like Spinraza and Evrysdi are transforming SMA prognosis. These treatments boost SMN protein levels, slow disease progression, and extend lifespan — especially when started early.

Comprehensive care including respiratory support, physiotherapy, and nutrition management further enhances survival and quality of life.

Conclusion

Spinal Muscular Atrophy (SMA) is a challenging condition that affects muscle strength and movement, but with advancements in treatment & support, there is hope for those living with it. Early diagnosis and timely access to appropriate therapies can significantly impact the management of rare diseases and enhance quality of life.

In India, where the cost of SMA treatment can be overwhelming, fundraising platforms play a crucial role. They offer a medium for communities to come together and raise the necessary funds to support families & individuals facing these high costs. By contributing to or organizing medical fundraising efforts, we can ensure that those with SMA receive the care they need & reduce the financial burden on their families.

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