Summary about Disease
Spinal Muscular Atrophy (SMA) is a genetic neuromuscular disease characterized by the progressive loss of motor neurons (nerve cells) in the spinal cord and brainstem. These motor neurons control voluntary muscle movements, such as crawling, walking, head and neck control, and swallowing. The loss of these neurons leads to muscle weakness and atrophy (wasting). SMA is a leading genetic cause of infant mortality. The severity of SMA varies depending on the type and age of onset.
Symptoms
Symptoms of SMA vary greatly depending on the type of SMA and the age of onset. Common symptoms include:
Muscle weakness: This is the primary symptom and is typically symmetrical (affects both sides of the body equally). It's usually more pronounced in the muscles closer to the center of the body (proximal muscles), such as those in the shoulders, hips, and back.
Muscle atrophy (wasting): Muscles become smaller and weaker due to lack of nerve stimulation.
Floppiness (hypotonia): Infants may appear "floppy" or have reduced muscle tone.
Difficulty breathing: Weakness of respiratory muscles can lead to breathing problems, especially in more severe types.
Difficulty swallowing and feeding: Weakness of the muscles involved in swallowing can cause problems with feeding and an increased risk of aspiration (food entering the lungs).
Tremors: Fine trembling of the hands or fingers may be observed.
Skeletal abnormalities: Scoliosis (curvature of the spine) and joint contractures (shortening and tightening of muscles and tendons) can develop over time.
Delayed motor milestones: Infants and children may be slow to reach developmental milestones such as sitting, crawling, and walking.
Causes
SMA is caused by a genetic defect in the SMN1 (Survival Motor Neuron 1) gene located on chromosome 5. This gene produces a protein called SMN (survival motor neuron) which is crucial for the health and function of motor neurons. In individuals with SMA, both copies of the *SMN1* gene are either missing or mutated, leading to insufficient production of functional SMN protein. A backup gene, *SMN2*, also produces SMN protein, but at much lower levels. The number of copies of the *SMN2* gene a person has can influence the severity of SMA; individuals with more copies of *SMN2* tend to have milder symptoms. SMA is inherited in an autosomal recessive pattern. This means that both parents must be carriers of the defective gene in order for their child to be affected. Carriers typically do not have any symptoms of SMA. If both parents are carriers, there is a 25% chance with each pregnancy that their child will have SMA, a 50% chance that their child will be a carrier, and a 25% chance that their child will inherit two normal copies of the gene.
Medicine Used
Several medications are approved for the treatment of SMA:
Nusinersen (Spinraza): This is an antisense oligonucleotide that modifies the splicing of the SMN2 gene to increase the production of functional SMN protein. It is administered by intrathecal injection (injection into the fluid surrounding the spinal cord).
Onasemnogene abeparvovec-xioi (Zolgensma): This is a gene therapy that delivers a functional copy of the SMN1 gene to the patient's cells using a viral vector. It is administered as a one-time intravenous infusion.
Risdiplam (Evrysdi): This is an SMN2 splicing modifier, similar to nusinersen, but it is administered orally as a liquid. These medications aim to increase the amount of functional SMN protein in the body, which can improve motor function and slow the progression of the disease. Other treatments and therapies include physical and occupational therapy, respiratory support, and nutritional support.
Is Communicable
No, Spinal Muscular Atrophy (SMA) is not communicable. It is a genetic disease caused by a mutation in the SMN1 gene, and it is inherited from parents. It cannot be spread from person to person through any form of contact.
Precautions
Since SMA is not communicable, standard infection control precautions do not apply. However, there are important considerations for individuals with SMA and their caregivers:
Respiratory Support: Individuals with SMA, particularly those with more severe types, may have weakened respiratory muscles and be more susceptible to respiratory infections. Precautions to minimize exposure to respiratory illnesses are important, such as avoiding close contact with sick individuals, practicing good hand hygiene, and receiving recommended vaccinations (e.g., flu vaccine, pneumococcal vaccine).
Swallowing Difficulties: If swallowing is impaired, precautions to prevent aspiration (food or liquid entering the lungs) should be taken during feeding. This may include modified food textures, specialized feeding techniques, and monitoring for signs of aspiration.
Skin Care: Individuals with limited mobility are at risk for pressure sores. Regular repositioning and good skin care are essential to prevent skin breakdown.
Fall Prevention: Muscle weakness and balance problems increase the risk of falls. Home modifications and assistive devices can help to prevent falls.
Physical and Occupational Therapy: Regular physical and occupational therapy can help to maintain muscle strength and function, improve mobility, and prevent contractures. Following the therapist's recommendations for exercises and positioning is important.
How long does an outbreak last?
SMA is not an infectious disease and does not involve outbreaks. Therefore, this question does not apply.
How is it diagnosed?
SMA is typically diagnosed through a combination of clinical evaluation and genetic testing.
Clinical Evaluation: A physician will assess the patient's symptoms, muscle strength, reflexes, and motor development.
Genetic Testing: A blood test is used to analyze the SMN1 gene. In most cases, individuals with SMA have a deletion or mutation in both copies of the *SMN1* gene. The number of copies of the *SMN2* gene may also be determined, as this can influence the severity of the disease.
Electromyography (EMG): An EMG may be performed to assess the electrical activity of muscles and nerves. This can help to confirm the diagnosis and rule out other neuromuscular disorders.
Muscle Biopsy: In some cases, a muscle biopsy may be performed to examine muscle tissue under a microscope. This is less common now that genetic testing is readily available.
Timeline of Symptoms
The timeline of symptoms varies greatly depending on the type of SMA:
SMA Type 0: Symptoms are present at birth or shortly thereafter. Severe muscle weakness, respiratory failure, and absent reflexes are typical. Life expectancy is very short.
SMA Type 1 (Werdnig-Hoffmann disease): Symptoms typically appear within the first 6 months of life. Infants have severe muscle weakness, difficulty breathing and swallowing, and are unable to sit independently.
SMA Type 2 (Intermediate SMA): Symptoms usually appear between 6 and 18 months of age. Children can sit independently but are unable to stand or walk independently.
SMA Type 3 (Kugelberg-Welander disease): Symptoms usually appear after 18 months of age, but can also appear in adolescence or adulthood. Individuals can walk independently at some point, but may experience progressive muscle weakness and loss of motor skills over time.
SMA Type 4 (Adult-onset SMA): Symptoms appear in adulthood. Individuals experience gradual muscle weakness and fatigue.
Important Considerations
Early Diagnosis and Treatment: Early diagnosis and treatment of SMA are crucial to maximizing outcomes. Newborn screening for SMA is becoming increasingly common, allowing for early intervention.
Multidisciplinary Care: Management of SMA requires a multidisciplinary approach, involving neurologists, pulmonologists, gastroenterologists, orthopedic surgeons, physical therapists, occupational therapists, speech therapists, and other specialists.
Genetic Counseling: Genetic counseling is recommended for families affected by SMA to understand the inheritance pattern and the risk of having another child with SMA.
Research: Ongoing research is focused on developing new and improved treatments for SMA, as well as better understanding the underlying mechanisms of the disease.
Support Groups: Support groups can provide valuable emotional support and information for individuals with SMA and their families.