What is SMA Disease Type 2?

Spinal Muscular Atrophy is the most common genetic cause of infant mortality. SMA is caused by a missing or faulty SMN1 gene, which is crucial for muscle function. But not all SMA conditions are the same. Among its various forms, SMA disease Type 2 is a condition that typically develops in early childhood and progresses over time. Unlike SMA Type 1, which is more severe, SMA Type 2 allows children to sit but often prevents them from walking.

In this blog, we will learn about what is SMA, especially SMA disease Type 2, its symptoms, causes, diagnosis, and available treatments. If you are a concerned parent, a caregiver, or simply curious, this guide will help you understand everything about spinal muscular atrophy SMA.

Read more: What is Spinal Muscular Atrophy (SMA)?

What is Spinal Muscular Atrophy?

SMA is a group of genetic (inherited) neuromuscular disorders that cause certain muscles to become weak and waste away, a process known as atrophy. The SMA full form in medical is Spinal Muscular Atrophy, and it’s one of the most serious conditions in the category of motor neuron diseases.

Spinal Muscular Atrophy causes the symptoms typically due to the loss of a specific type of nerve cell in the spinal cord called lower motor neurons, also known as anterior horn cells. These cells are responsible for sending signals from the spinal cord to the muscles. Without them, muscles no longer receive the nerve messages that allow them to move, leading to progressive muscle weakness.

In most cases, SMA symptoms are more severe in the proximal muscles, those closer to the body’s centre, such as the shoulders, hips, and back, than in the distal muscles, like the hands and feet. This muscle weakness typically worsens over time, making early SMA diagnosis and treatment critical.

There are different spinal muscular atrophy types, including SMA type 1, SMA type 2, and SMA type 3, each with varying degrees of severity and age of onset. In this blog, our focus will be on SMA disease type 2, one of the most common forms seen in children.

Understanding Spinal Muscular Atrophy Types

Spinal Muscular Atrophy (SMA) is not a single type of condition. It is classified into different SMA types, based on the age of onset and the severity of symptoms. The main SMA types include:

SMA Type 0 (Prenatal SMA)

Spinal Muscular Atrophy type 0 is the rarest and most severe form. It affects babies before birth, and symptoms are visible at or even before delivery. Infants may have severely weak muscles, joint deformities, and breathing problems. Unfortunately, babies with type 0 often survive only a few weeks or months.

SMA Type 1 (Werdnig-Hoffmann Disease)

This is the most severe and common form, typically appearing before the age of 6 months. Babies with Spinal Muscular Atrophy type 1 often struggle to hold up their heads, sit without support, or even breathe easily. It progresses rapidly, and without treatment, life expectancy is very limited.

SMA Type 2

This is one of the sma types that usually appears between 6 and 18 months of age. Children with SMA type 2 can typically sit without support but cannot stand or walk unaided. While it is less severe than type 1, SMA disease type 2 still causes progressive muscle weakness, especially in the legs and upper arms. With proper care and new treatment options, many individuals live into adolescence or adulthood.

SMA Type 3 (Kugelberg-Welander Disease)

SMA type 3 has a later onset, usually after 18 months or even into the teen years. People with this type can stand and walk, but may lose that ability over time. It tends to be milder than types 1 and 2.

SMA Type 4 (Adult-Onset SMA)

This rare form appears after the age of 30. Spinal Muscular Atrophy type 4 causes slowly progressing muscle weakness, often affecting the lower body. It is the mildest form and usually does not impact life expectancy.

Recognizing the SMA types is essential for choosing the right treatment approach and setting realistic expectations for physical development and daily life.

Detailed View of SMA Disease Type 2 

SMA Type 2 is often diagnosed in children between 6 to 18 months of age, making it the most common type in this age group. It is considered moderate in severity compared to SMA Type 1, yet it still leads to significant challenges in muscle control and mobility.

Unlike SMA Type 1, where infants cannot sit up or control basic movements, children with SMA Type 2 can sit independently but struggle with standing or walking without assistance. Muscle weakness usually begins in the proximal muscles (those closer to the body’s centre, like the hips and shoulders), which makes daily activities like standing or walking a major hurdle.

As the condition progresses, children with SMA type 2 often lose the ability to stand or walk and may require assistive devices, such as wheelchairs, for mobility. The weakness typically worsens over time, especially if not properly managed, and it can affect breathing and swallowing muscles in advanced cases.

Spinal Muscular Atrophy Symptoms for Type 2

The SMA symptoms for type 2 typically emerge between 6 and 18 months of age. Unlike SMA type 1, where SMA symptoms appear earlier and are more severe, children with SMA type 2 experience a moderate progression of muscle weakness and motor difficulties.

Here are the major SMA symptoms for Type 2 that parents and caregivers should be aware of:

• Muscle Weakness:-
  One of the major SMA symptoms is muscle weakness, which often starts in the proximal muscles, those closer to the body’s center, such as the hips, thighs, and shoulders. Spinal Muscular Atrophy causes difficulty for children to sit up, crawl, or eventually stand or walk independently.
  
• Delayed Motor Skills:-
  Spinal Muscular Atrophy causes the children to experience delays in motor milestones, such as sitting up, crawling, or walking. Sitting may be achievable, but standing and walking are often impossible without support as muscle weakness progresses.
  
• Spinal Curvature (Scoliosis):-
  As the muscles that support the spine weaken, scoliosis (curvature of the spine) often develops. This can worsen as the Spinal Muscular Atrophy Type 2 progresses, leading to postural abnormalities that affect overall mobility and comfort.
  
• Breathing Difficulties:-
  SMA type 2 can also impact the muscles used for breathing. This can lead to issues with respiratory function, especially during sleep. As the condition progresses, breathing support might be necessary.
  
• Hand Tremors (Fasciculations):-
  Some children with SMA type 2 experience muscle twitching or fasciculations, particularly in the hands or legs. These can be visible when the affected muscles are at rest and can contribute to additional challenges with fine motor skills.
  
• Difficulty Swallowing:-
  In more advanced cases of SMA type 2, swallowing difficulties may arise. This can cause issues with feeding and drinking, increasing the risk of choking or aspiration.
  
• Joint Deformities:-
  Weakness in muscles can lead to joint contractures, where the joints become stiff and immobile, especially in the hips, knees, and ankles. This can affect movement and cause discomfort.
  
• Fatigue:-
  Due to the increased effort needed to move weakened muscles, individuals with Spinal Muscular Atrophy type 2 often experience fatigue more quickly than other children. They may require more rest than their peers to recover from physical activity.
  

Causes of the Genetics of SMA

The most common cause of SMA types 1–4 is a mutation in the SMN1 gene located on chromosome 5. People have two copies of the SMN1 gene, one on each chromosome 5. In 94% of SMA cases, the mutation involves a deletion in exon 7 of the SMN1 gene. This deletion prevents the gene from making the necessary SMN protein (Survival of Motor Neuron), which is crucial for the health of motor neurons.

Without enough SMN protein, motor neurons deteriorate, leading to muscle weakness. The severity of SMA can vary based on the number of copies of another gene, SMN2, which also produces SMN protein. However, most of the protein from SMN2 is not fully functional, and only 10–15% of it is useful.

More SMN2 gene copies = milder symptoms

Fewer copies of SMN2 = more severe disease progression

In general, people with three or more SMN2 gene copies tend to experience a milder form of SMA.

Other Genetic Spinal Muscular Atrophy Causes

X-linked SMA: This form is caused by mutations in a gene on the X chromosome, known as UBE1. Males with this mutation are often severely affected, while females may be carriers.

DYNC1H1-related SMA: A rarer form of SMA can be caused by mutations in the DYNC1H1 gene on chromosome 14, leading to SMA-LED. This form is dominantly inherited, meaning that only one copy of the mutated gene is needed to cause the disease.

Why Does SMA Vary in Severity?

The severity of SMA can vary widely between individuals. This is due to both genetic factors and disease modifiers. Although the SMN1 gene mutation causes SMA, the number of SMN2 gene copies plays a crucial role in determining how severe the condition will be. More SMN2 copies result in higher amounts of functional SMN protein, which can delay the onset of symptoms and reduce the severity of the disease.

In addition to SMN2, certain proteins like plastin 3 and ZPR1 have been identified as disease modifiers, affecting the course of SMA. These proteins may influence the severity and onset of symptoms, and ongoing research into them could provide new therapeutic targets.

Inheritance Pattern of SMA

SMA types 1-4, caused by SMN1 gene mutations, follow an autosomal recessive inheritance pattern. This means that a child needs to inherit two copies of the mutated SMN1 gene (one from each parent) to develop the disease. Carriers, who have only one copy of the mutated gene, do not show symptoms but can pass the gene to their children.

• 25% chance of a child being affected if both parents are carriers
• 50% chance of a child being a carrier if one parent is a carrier

Genetic testing is available to identify carriers and diagnose SMA, including in unborn babies.

Diagnosis and Tests for SMA Disease Type 2 

SMA Disease Type 2 is usually diagnosed between 6 to 18 months, when the child does not achieve normal movement development for their age. Spinal Muscular Atrophy (SMA) Type 2 is typically diagnosed between the ages of 6 months and 2 years when a child fails to meet expected milestones for movement development. Children with SMA type 2 may show delayed motor skills, such as difficulty sitting, crawling, or standing, which often prompts doctors to investigate further.

Genetic Testing for SMA Type 2 Diagnosis

The most reliable method for Spinal Muscular Atrophy diagnosis, especially for SMA type 2, is through genetic testing for the SMN1 gene mutation. This test looks for mutations in the SMN1 gene located on chromosome 5, which causes the loss of motor neurons and muscle weakness. If the SMN1 gene mutation is present, it confirms the diagnosis of SMA type 2.

Challenges in the Diagnosis of SMA Disease Type 2

Although genetic testing is the gold standard for confirming SMA, the disease can sometimes be confused with other neuromuscular disorders due to the milder symptoms of SMA type 2 compared to the more severe forms, like SMA type 1. In some cases, apart from SMA tests like genetic testing, doctors may also consider a muscle biopsy from the leg as an additional diagnostic tool to examine muscle tissue and confirm the presence of muscle atrophy.

Prenatal Genetic Testing for SMA Disease Type 2

With advancements in prenatal genetic testing, SMA diagnosis is possible before birth or in the first few months of life. Prenatal screening for SMA allows parents to know whether their baby has inherited the SMN1 gene mutation and to prepare for early intervention. These tests are becoming increasingly common and accurate, providing quicker and more reliable diagnoses.

In many countries, SMA newborn screening is recommended, which can detect the condition at birth, enabling immediate diagnosis and timely treatment to prevent or slow down disease progression.

Why Early Diagnosis is Crucial

The early detection of SMA type 2 is critical, as early intervention with SMA treatments like Spinraza, Zolgensma, or Evrysdi has been shown to improve motor function and overall quality of life. Early treatment can help slow the progression of muscle weakness and increase the chances of reaching important developmental milestones.

Spinal Muscular Atrophy Treatment

Although there is currently no cure for SMA Type 2, recent advances in SMA diagnosis and treatment have significantly improved both motor function and life expectancy for those affected. With early diagnosis through newborn screening, children can begin treatment even before symptoms arise, greatly enhancing the Spinal Muscular Atrophy life expectancy.

Disease-Modifying Treatments for SMA Type 2

Several newer Spinal Muscular Atrophy treatments can help increase the levels of functional SMN protein in the body, which is essential for motor neuron survival. These treatments have proven to help children with SMA Type 2 achieve or maintain key motor milestones:

Nusinersen (Spinraza): This injectable SMA medicine stimulates the production of functional SMN protein in the central nervous system (CNS), including the brain and spinal cord. Administered by a healthcare professional, Spinraza is injected directly into the fluid surrounding the spinal cord at regular intervals. This treatment has been shown to improve motor function in children with SMA.

Risdiplam (Evrysdi): Unlike Spinraza, Evrysdi is an oral SMA medicine that helps increase functional SMN protein not only in the CNS but throughout the entire body. Taken daily, Evrysdi is an important option for SMA Type 2 patients who may not be suitable candidates for injections.

Onasemnogene abeparvovec (Zolgensma): Zolgensma is an SMA gene therapy that works as a replacement therapy specifically for children under 2 years old. Administered as a one-time intravenous (IV) infusion, Zolgensma works by replacing the missing or defective SMN1 gene, enabling the production of the crucial SMN protein.

These disease-modifying Spinal Muscular Atrophy treatments may help SMA Type 2 children achieve or sustain motor milestones, allowing them to lead a better quality of life. However, it’s important to discuss with your child’s healthcare provider to determine if and when these treatments are appropriate for your child.

Read more on: SMA Injection Cost – Why It Is the Costliest Injection in the World?

Supportive Care for SMA Type 2

In addition to disease-modifying SMA treatments, children with SMA Type 2 may require supportive care to manage their symptoms and ensure overall well-being. This may include:

• Mechanical ventilation is used to assist with breathing if the respiratory muscles are weakened.
• Respiratory therapy helps maintain lung function.
• Feeding support for children who have difficulty swallowing or feeding independently.
• Physical and occupational therapy to promote mobility, strengthen muscles, and enhance daily functioning.
• Assistive devices for mobility (such as wheelchairs or walkers) and communication (such as speech devices) can improve independence and quality of life.
  

Real Story: Manha SMA Patient

Manha, a child diagnosed with SMA disease Type 2, has faced numerous challenges throughout her life. Like many children with SMA, Manha’s journey began with a diagnosis of delayed motor milestones around the age of 6 months. Her parents noticed that she had difficulty sitting, crawling, and achieving other important motor skills expected of a child her age.

Thanks to early SMA diagnosis through newborn screening, Manha was able to start disease-modifying SMA treatments like Spinraza and Evrysdi soon after her diagnosis. This early intervention has helped improve her motor function and has given her the opportunity to achieve some motor milestones she might have otherwise missed.

Throughout her treatment, Manha has also received ongoing supportive care, including physical therapy, which has helped strengthen her muscles and improve her coordination. Despite the challenges she faces daily, Manha’s family continues to provide her with the necessary resources, including assistive devices for mobility and communication, to ensure she leads a fulfilling life.

Conclusion

In this blog, we understood the SMA meaning, how Spinal Muscular Atrophy (SMA) Type 2 is a genetic neuromuscular disorder. It significantly impacts motor function, but with early diagnosis and advanced treatments, the outlook for children with this condition has greatly improved. Although there is no cure for SMA disease Type 2, disease-modifying treatments such as Spinraza, Evrysdi, and Zolgensma offer hope, helping to enhance motor function, prolong life expectancy, and allow children to reach important milestones.

Through advancements in genetic testing and newborn screening, SMA can be identified early, ensuring that children receive the care they need before SMA symptoms worsen. Supportive care, including physical therapy, feeding support, and assistive devices, plays a crucial role in improving the quality of life for those living with SMA Type 2.

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