spinal muscular atrophy

Spinal muscular atrophy (SMA) is a group of hereditary diseases that affect motor neurons, which are specialized nerve cells responsible for controlling voluntary muscle movement [1]. This genetic condition causes certain muscles to become weak and waste away due to the loss of nerve cells in the spinal cord called lower motor neurons [5].

There are five subtypes of SMA, each with varying degrees of severity and age of onset [2]. The disease can affect a child's ability to walk, sit, or even breathe, depending on the subtype and severity [6]. In someone with SMA, the nerves that control muscle movement (the motor neurons) are affected, leading to progressive muscle weakness and atrophy [7].

SMA is a rare genetic condition that can cause muscle weakness, which gets worse over time. However, there are medicines and other treatments available to manage the symptoms and improve quality of life [8]. The disease can affect muscles throughout the body, weakening them due to nerve cell degeneration in the spinal cord [9].

Symptoms may appear at any age and include progressive loss of coordination of gait, hands, speech, and eye movements. Early diagnosis and treatment are crucial for improving outcomes and managing symptoms effectively.

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Spinal muscular atrophy (SMA) is a genetic disorder that affects the nerve cells responsible for controlling voluntary muscle movement. The signs and symptoms of SMA can vary in severity, but they typically involve weakness or wasting of the muscles.

Common Signs and Symptoms:

• Muscle weakness: This is the most common symptom of SMA, and it can affect any muscle group, including the arms, legs, and respiratory muscles.
• Floppiness or little movement in infancy: Infants with SMA may have difficulty moving their arms and legs, and they may appear "floppy" due to weak muscles.
• Poor head control: Babies with SMA may have trouble holding their heads up or maintaining good posture.
• Weak suck or feeding difficulties: Some infants with SMA may have trouble sucking or feeding properly due to weak facial muscles.
• Breathing problems: As the disease progresses, people with SMA may experience breathing difficulties due to weakened respiratory muscles.
• Scoliosis (curved spine): Weakened back muscles can lead to a curved spine in some individuals with SMA.

Progression of Symptoms:

The symptoms of SMA can progress over time, and they can vary depending on the type and severity of the disease. In general, people with SMA experience:

• Gradual weakening of muscles
• Decreased muscle tone (hypotonia)
• Muscle wasting (atrophy)
• Breathing difficulties
• Scoliosis or other musculoskeletal problems

References:

• [1] Decreased fetal movements. Arthrogryposis. Decreased muscle tone (hypotonia). Severe muscle weakness. Severe breathing issues.
• [2] Symptoms of SMA type 1 include: floppy arms and legs, difficulty sitting up, crawling, or walking.
• [3] Muscle weakness – such as floppy or weak arms and legs; movement problems – such as difficulty sitting up, crawling, or walking.
• [4] Scoliosis (a curved spine) if the back muscles are weak; aspiration (breathing in) of fluid or food.
• [5] Loss of lower motor neurons leads to progressive muscle weakness, muscle wasting (atrophy), and low muscle tone (hypotonia).
• [6] Insufficient levels of SMN protein leads to loss of motor neurons in the spinal cord and causes weakness and wasting of the skeletal muscles.

Spinal muscular atrophy (SMA) can be diagnosed through various tests, which are essential for confirming the presence of this genetic disorder.

Genetic Testing

Genetic testing is considered the most accurate way to diagnose SMA. This test involves analyzing a blood sample or tissue from the affected individual to identify any mutations in the SMN1 gene, which is responsible for producing the survival motor neuron protein (SMN) [1]. Genetic testing can confirm 95% of SMA cases by identifying problems with the SMN1 gene [4].

Other Diagnostic Tests

In addition to genetic testing, other diagnostic tests may be performed to rule out or confirm SMA. These include:

• Electromyography (EMG): This test measures the electrical activity of a muscle or group of muscles to assess nerve function [3].
• Nerve Conduction Study (NCS): This test evaluates the speed and strength of electrical signals traveling through nerves [3].
• Muscle Biopsy: A sample of muscle tissue is taken for examination under a microscope to look for signs of muscle damage or degeneration [3].

Newborn Screening

In the United States, all 50 states now routinely screen newborns for SMA as part of their universal newborn screening programs. This blood test can detect problems with the SMN1 gene and confirm approximately 95% of SMA cases [4].

Carrier Testing

Carrier testing is available through a simple blood test that detects the most common mutation associated with SMA. This test can identify individuals who carry the mutated gene, even if they do not show symptoms themselves [5].

In summary, diagnostic tests for spinal muscular atrophy include genetic testing, electromyography (EMG), nerve conduction study (NCS), muscle biopsy, newborn screening, and carrier testing.

References:

[1] Context 1 [2] Context 2 [3] Context 3 [4] Context 4 [5] Context 5

Spinal muscular atrophy (SMA) is a rare and often fatal genetic disorder that affects the nerve cells responsible for controlling voluntary muscle movement. Fortunately, several drug treatments have been approved to manage this condition.

Approved Treatments

There are currently three SMN-enhancing (SMA) spinal muscular atrophy treatments approved by the U.S. Food and Drug Administration (FDA):

• Nusinersen (Spinraza): approved in 2016 for use in children (including newborns) and adults with SMA [8].
• Onasemnogene abeparvovec (Zolgensma): a gene therapy that replaces the faulty SMN1 gene, approved in 2019 [6].
• Risdiplam (Evrysdi): an orally administered drug that works by increasing the production of the survival motor neuron protein, approved in 2020 for use in children 2 months and older [4].

Additional Treatment Options

Other treatments are also available to help people with SMA have the best possible quality of life. These include:

• Physical therapy: to maintain muscle strength and mobility
• Occupational therapy: to improve daily living skills and independence
• Speech therapy: to address communication difficulties
• Respiratory care: to manage breathing problems

Current Research

Researchers are continually exploring new treatments for SMA, including gene therapies and small molecule drugs. These advancements hold promise for improving the lives of people with this condition.

References:

[1] Crisafulli S (2023) - To date, three orphan drugs have been approved for the treatment of SMA: nusinersen, an antisense oligonucleotide, onasemnogene abeparvovec, a gene therapy, and risdiplam, an orally administered drug. [2] FDA approval of Evrysdi (risdiplam) in 2020 [3] Available Treatments for SMA [4] Risdiplam is the third treatment for SMA and was FDA approved in 2020 for use in children 2 months and older. [5] Evrysdi is a prescription medicine used to treat spinal muscular atrophy (SMA) in children and adults. [6] Zolgensma, marketed by Novartis Gene Therapies®, replaces the faulty SMN1 gene. [7] Risdiplam (Evrysdi™) works by increasing the production of the survival motor neuron protein. [8] FDA approval of nusinersen (Spinraza) in 2016

Spinal Muscular Atrophy (SMA) has several differential diagnoses, which are conditions that can present similarly to SMA and must be considered in the diagnostic process.

Conditions to Consider

• Amyotrophic Lateral Sclerosis (ALS): Also known as Lou Gehrig's disease, ALS is a progressive neurological disorder that affects nerve cells in the brain and spinal cord. Like SMA, ALS leads to muscle weakness and atrophy, but it primarily affects the motor neurons in the brain rather than the spinal cord [1].
• Congenital Muscular Dystrophy: This is a group of rare genetic disorders characterized by muscle weakness and wasting that are present at birth. While some forms of congenital muscular dystrophy can mimic SMA, they often have distinct clinical features such as muscle cramps and cataracts [2].
• Congenital Myopathies: These are a group of rare genetic disorders that affect the muscles and can cause weakness and wasting. Some types of congenital myopathies can present similarly to SMA, but they often have distinct histological features on muscle biopsy [3].
• Disorders of Carbohydrate Metabolism: Certain metabolic disorders, such as Pompe disease, can mimic the clinical presentation of SMA. These conditions are caused by enzyme deficiencies that affect carbohydrate metabolism and can lead to muscle weakness and wasting [4].

Other Conditions

• Cerebral Palsy (Hypotonic Diplegia): This is a neurological disorder that affects movement and muscle tone in children. While it can cause muscle weakness, cerebral palsy typically presents with distinct clinical features such as spasticity and developmental delays [5].
• Transverse Myelitis: This is an inflammatory condition that affects the spinal cord and can cause muscle weakness and wasting. However, transverse myelitis often has distinct clinical features such as sensory loss and bladder dysfunction [6].

Diagnostic Considerations

The diagnosis of SMA typically involves a combination of clinical evaluation, family history, and genetic testing. A thorough physical examination and medical history are essential to rule out other conditions that may mimic SMA. Genetic testing for the SMN1 gene can confirm the diagnosis of SMA, but it is not always necessary [7].

In conclusion, differential diagnoses for spinal muscular atrophy include a range of conditions that can present similarly to SMA. A thorough clinical evaluation and genetic testing are essential to accurately diagnose and differentiate these conditions.

References:

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