by What is Spinal Muscular Atrophy?
Spinal muscular atrophy (SMA) is a genetic disease that affects the nerves in the spinal cord that control muscle movement. It is caused by a defect or mutation in the survival motor neuron 1 (SMN1) gene. This gene provides instructions for producing a protein that is essential for the function and survival of motor neurons which interact with voluntary muscles. Without this protein, motor neurons die, causing progressive muscle weakness and atrophy. There are different types and severities of SMA based on age of onset and highest level of motor function achieved.
Types and Severity
Spinal Muscular Atrophy is classified into four main types – Type I through Type IV – based on age of onset and highest physical milestone achieved.
Type I, also called Werdnig-Hoffmann disease, is the most severe and common type of SMA. Symptoms begin before 6 months of age. Babies with Type I SMA never sit without support and have severe weakness of the muscles responsible for breathing and swallowing.
Type II SMA has an age of onset between 6-18 months. Affected individuals never stand or walk without assistance. Respiratory problems are a major health concern.
Type III SMA, also known as Kugelberg-Welander disease or juvenile SMA, has an onset after 18 months of age. Affected individuals are able to stand and walk but may lose this ability over time.
Type IV SMA has the least severe symptoms. Onset is in adulthood but symptoms are mild and progression slow. Individuals are able to stand and walk normally but with some limitations of movement over time.
Causes and Genetics
Mutations in the SMN1 gene on chromosome 5 are responsible for all types of SMA. The SMN1 provides instructions for a protein called survival motor neuron (SMN) which is essential for motor neuron function and survival. Approximately 95% of individuals with SMA are missing or have defects in both copies of the SMN1 gene.
There is a homologous gene called SMN2 which produces a small amount of functional SMN protein but not enough to prevent SMA. The number of copies of SMN2 a person has determines disease severity in SMA. More copies generally result in less severe or later onset forms.
Diagnosis
If SMA is suspected based on clinical symptoms and family history, genetic testing is required for definitive diagnosis. A blood sample is analyzed to identify mutations or defects in the SMN1 and SMN2 genes. In severe forms like Type I, diagnosis can be as early as a few months of age following initial symptoms. In milder forms diagnosis may occur later once muscle weakness progresses.
Electromyography (EMG) assesses electrical activity in muscles and nerves and can reveal abnormalities indicative of motor neuron loss in SMA. Additional tests rule out other disorders with similar muscle weakness presentations.
Treatment and Management
While there is currently no cure for SMA, treatments can help manage symptoms and improve quality of life. Care focuses on maintaining nutrition, mobility, and respiratory health through physical and occupational therapy, bracing, supportive equipment like wheelchairs, and respiratory care including cough assistance and ventilation if needed.
Gene replacement therapy is a promising new treatment option for SMA. The first medication approved for SMA, nusinersen, is an antisense drug that modifies SMN2 splicing to increase full-length SMN protein production. Treatment aims to prevent motor neuron loss through increasing SMN levels in motor neurons. Early studies show improvements in motor function milestones maintained in treated individuals after several years.
Additional therapies in development target increasing SMN protein levels through different mechanisms including drugs and gene therapy. Clinical trials continue to evaluate new treatments and earlier intervention to potentially alter the disease course in more severe forms of SMA. Palliative care also plays an important role in symptom management.
Prognosis
Prognosis is variable based on type and severity of SMA. In severe Type I, without intervention median survival is only a few months due to respiratory failure. With treatments to support breathing and nutrition, average lifespan has increased to 2-4 years.
Type II and III individuals have better long-term survival, often into adulthood with risk of complications from reduced mobility over time if unsupported. Prognosis is best for Type IV SMA where average lifespan is normal. Continued advancements in treatments offer hope for further gains in managing disease progression and improving quality of life across all SMA types.
Understanding this complex genetic disorder provides insight into current and developing options to treat SMA and support affected individuals at each stage of life. As research uncovers new targets to boost the survival of motor neurons, prognosis continues improving.
