Introduction
Spinal muscular atrophy type 1 (SMA-1), also referred to as Werdnig Hoffmann disease, is a degenerative neuromuscular condition that affects the control of voluntary movements in the body. The damage and loss of motor neurons cause this condition. Common symptoms of Werdnig Hoffmann disease include difficulty with eating, breathing, and limb movement. Approximately 60 percent of SMA patients have Werdnig-Hoffman disease. This form of SMA manifests in infants at birth or within the first six months of life. It causes difficulties with swallowing and sucking, along with a failure to reach typical developmental milestones such as holding up their heads or sitting. As the muscles continue to deteriorate, the risk of respiratory infections and pneumothorax increases, and most children with type 1 SMA do not survive past their second birthday.
What Are the Symptoms of Spinal Muscular Atrophy Type 1?
Spinal Muscular Atrophy (SMA) is a condition that weakens muscles over time. SMA1 is a severe form of the condition that affects the muscles responsible for breathing, making it difficult for children with the condition to live beyond the age of two. Infants with SMA1 are often weak from birth and have difficulty feeding, but their cognitive, mental, and emotional development is generally unaffected. There is no cure for SMA, but treatments can improve symptoms and extend the child's life. Children with different types of SMA may have difficulty with movements such as head control, sitting up, walking, and swallowing, with the severity of the condition depending on the specific type of SMA they have.
Additional symptoms of SMA1:
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Muscle weakness.
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Changes in the shape of limbs due to muscle weakness.
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Lack of ability to move the limbs.
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Scoliosis (curvature of the spine over time).
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Congenital (present at birth) bone fractures.
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Thin ribs.
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Difficulty with standing, walking, and sitting.
Severe symptoms of SMA1:
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Aspiration pneumonia (can lead to severe conditions and death).
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Heart defects (including ventricular septal defects - abnormal connections between the ventricles of the heart).
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Possible involvement of the autonomic nervous system.
SMA is a degenerative condition, meaning symptoms will worsen over time.
What Are the Causes and Risk Factors of Spinal Muscular Atrophy Type 1?
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SMA affects both infants and children due to the breakdown of nerve cells in the brain and spinal cord.
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SMA1 is a genetic condition caused by abnormal genes, specifically the survival motor neuron (SMN) gene.
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There are two forms of the SMN gene: SMN1 and SMN2, with SMN1 causing the disease and SMN2 affecting its severity.
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Other gene mutations may also play a role in determining the severity of SMA1.
Spinal muscular atrophy affects roughly 1 in 10,000 live births and is found equally in both males and females. Half of the infants born with the disease do not survive. Those with a family history of the condition are at a greater risk of passing it on to their offspring and may opt for genetic testing before conception. Carriers can be identified through a blood test. If both parents are carriers, the risk of having a child with the disease is 25 percent. To decrease the risk, they may opt for in vitro fertilization or sperm donation.
What Are the Methods for Diagnosing Spinal Muscular Atrophy Type 1?
A diagnosis of SMA1 can be made based on observation of symptoms by a parent or caregiver or through newborn screening, which added SMA to its screening guidelines in 2018. A doctor will then conduct a medical evaluation, which includes reviewing the child's and family's medical history, performing a physical examination, checking for weak or floppy muscles and tongue twitching, and testing muscle reflexes. Additional tests may also be requested to aid in the diagnosis.
Diagnostic tests for SMA may include:
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Blood test to check for creatine kinase levels, which can indicate muscle deterioration.
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Muscle biopsy to look for specific characteristics of SMA, although it is no longer sufficient for diagnosis.
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Electromyography (EMG) to evaluate muscle and nerve health.
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Molecular genetic testing to detect single gene changes.
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Additional genetic testing during pregnancy, such as amniocentesis or chorionic villus sampling, for families with a history of SMA.
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A positive newborn screening result may suggest SMA, but further testing, including additional bloodwork, physical exams, and genetic testing, is needed to confirm the diagnosis and determine the type and severity of SMA.
What Treatment Options Are Available for Spinal Muscular Atrophy Type 1?
Unfortunately, Werdnig-Hoffmann's disease has no cure yet. However, the treatment focuses on managing the symptoms of the condition. The Food and Drug Administration (FDA) has approved some new gene replacement therapies and disease-modifying therapies to help patients. One of the recent gene replacement therapies is Zolgensma (onasemnogene neparvovec-xioi), which replaces the defective or missing SMN1 with a functioning copy through an infusion. The new gene increases the SMN protein levels, which may lead to improved motor neuron function and increased survival. This therapy is intended for children who are younger than two years.
In addition, there are disease-modifying therapies that can help stimulate the production of SMN protein. Spinraza (nusinersen) has been approved for pediatric and adult patients, and it is injected into the space around the spinal canal. Another medication called Evrysdi (risdiplam) is prescribed for adults and children who are younger than two months, and it is taken daily by mouth. These treatments aim to provide relief and improve the quality of life for patients with Werdnig-Hoffmann disease.
Additional treatment options aim to provide support for issues related to feeding, breathing, and muscle weakness, which may include:
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Feeding Support: Children with difficulties in feeding can benefit from nutritional supplementation using percutaneous endoscopic gastrostomy tubes.
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Respiratory Support: Some children may require non-invasive breathing support if their respiratory muscles are affected early on. In more severe cases, ventilator support or a tracheostomy may be necessary.
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Muscle Support: Physical and occupational therapy can help improve muscle strength and flexibility, reduce joint stiffness and shortening, and minimize muscle, tendon, and tissue tightening. Assistive devices such as orthopedic braces, walkers, crutches, and wheelchairs can relieve pressure on affected joints and muscles and aid in movement. Scoliosis can be managed through surgical procedures.
Conclusion
In conclusion, Spinal Muscular Atrophy Type 1 (SMA-1), also known as Werdnig-Hoffmann disease, is a severe form of spinal muscular atrophy that affects voluntary movement control in the body. It is a degenerative genetic condition caused by abnormal genes, specifically the survival motor neuron (SMN) gene. Symptoms of SMA1 include muscle weakness, difficulty feeding and breathing, and developmental delays. Although there is currently no cure for SMA1, there are treatments available such as gene replacement therapy and disease-modifying medications, to manage symptoms and improve the quality of life for patients. A diagnosis of SMA1 can be made through observation of symptoms, newborn screening, and medical evaluations that may include blood tests, muscle biopsy, and genetic testing.
