- Who Is Affected
- Life Expectancy
Spinal muscular atrophy (SMA) is a debilitating disease that can be classified as a disability if symptoms are severe enough to cause significant impairments. SMA is hereditary and progressive, affecting both the central and peripheral nervous systems as well as voluntary muscle function.
The disease destroys motor neurons in the brainstem and spinal cord. Motor neurons are nerve cells responsible for skeletal muscle function, which include muscles in our arms, legs, chest, face, throat and tongue. Destruction of motor neurons disrupts the signals from the neurons to the muscles, and over time, the muscles gradually weaken and waste away (atrophy).
Who is affected by the disease?
The earlier in life the disease develops, the more severe it is:
- Approximately 60% of children with spinal muscular atrophy are born with the condition or develop it within the first 6 months of life. Children who develop spinal muscular atrophy after 6 months of age may be able to sit, depending on the severity, but most cannot walk.
- Children who develop the disease in their teens may initially have muscle weakness, but some eventually lose the ability to stand or walk.
- Adult onset of spinal muscular atrophy is rare and accounts for only about 5% of cases. People who develop spinal muscular atrophy as adults usually have muscle weakness, but most are able to manage the condition with treatment and exercise and remain mobile throughout their lives.
What are the signs and symptoms of spinal muscular atrophy?
Symptoms vary depending on the type and severity of the disease. Some people are never able to sit, stand or walk, and some lose these abilities gradually due to increasing muscle loss with age.
There are five types of spinal muscular atrophy:
Type 0 (SMA0)
Type 0 SMA is the rarest and most severe form, developing in babies in the womb. Fetal movement decreases and the baby is born with congenital heart defects, breathing difficulty, facial paralysis (facial diplegia), low muscle tone (hypotonia) and muscle weakness.
Type 1 (SMA1)
Also known as Werdnig-Hoffman disease, type 1 is a severe form of SMA that presents at birth or develops before a baby is six months old.
A child with type 1 SMA cannot sit up without support, and has trouble breathing, sucking and swallowing.
Type 2 (SMA2)
Type 2 accounts for about 20% of SMA cases and develops in children between 6-18 months of age. Also known as intermediate SMA or Dubowitz disease, type 2 SMA usually affects the legs more than the arms.
Type 3 (SMA3)
Children with type 3 SMA are able to stand and walk without support, but have difficulty running, climbing stairs and getting up from a chair. Most patients develop foot deformities, sideways spine curvature (scoliosis) and respiratory issues, and eventually become wheelchair-dependent.
Type 4 (SMA4)
Type 4 SMA is a mild form that develops in adulthood, usually after age 30. It accounts for less than 5% of all SMA cases.
What causes spinal muscular atrophy?
SMA is caused by inherited genetic defects. The most common form of the disease is caused by mutations in both copies of a gene known as survival motor neuron 1 (SMN1) on chromosome 5. The SMN1 gene encodes SMN protein, which maintains the health and normal functioning of motor neurons.
In 95%-98% of SMA cases, both copies of SMN1 gene are missing. About 2.5% have mutations that cause low production of SMN protein. A low level of SMN protein results in the destruction of motor neurons; as a result, the skeletal muscles weaken and waste away. This can lead to disability and even death in severe cases.
Many people with defective SMN1 usually have extra copies of the SMN2 gene, which mostly produces shorter-length SMN proteins. But it also produces a small amount (10%-15%) of functional full-length SMN protein. Some people may have even up to 8 copies of the SMN2 gene which increases the level of functional SMN protein and results in milder forms of the disease.
If someone has a mutation in one copy of a SMN1 gene, they may not be affected by the disease but can be a carrier and pass it on to their child. If both parents are carriers of SMN1, a child has about a 25% chance of developing SMA.
Less common forms of SMA are caused by mutations in other genes which include:
- VAPB gene on chromosome 20
- DYNC1H1 gene on chromosome 14
- BICD2 gene on chromosome 9
- UBA1 gene on X chromosome
With the exception of the UBA1 gene mutation on sex chromosome X, all others are autosomal recessive diseases. The 22 pairs of numbered chromosomes in the human cell are known as autosomes, except chromosomes X and Y which are the 23rd pair and determine gender.
We inherit a set of 23 chromosomes from each parent, with one copy of each gene on the 22 chromosomes from each parent, along with an X from our mother and an X or Y from our father. Autosomal recessive diseases occur when both the copies of the same gene are missing or defective.
How is spinal muscular atrophy diagnosed?
Diagnosis begins with a classification of SMA. Along with a clinical assessment of symptoms, diagnostic tests that can help confirm diagnosis include:
- Genetic testing with blood sample, which is the most accurate method.
- Blood test for an enzyme called creatine kinase (CK) which leaks out of muscles that break down. CK values are usually normal in SMA1, but are slightly elevated in SMA2 and SMA3 and can be confused with other muscle-wasting diseases.
- Electromyogram, a test that uses low electric pulses to measure electrical activity in the muscles.
- Nerve conduction study, which assesses the speed with which signals are transmitted through motor neurons.
- Muscle biopsy, in which muscle tissue sample is analyzed under a microscope.
Can spinal muscular atrophy be treated?
Treatment is highly effective in managing symptoms in SMA4 patients and most are mobile throughout their lives. Early diagnosis (before permanent motor neuron damage occurs) and appropriate treatment can improve outcomes for patients with SMA2 and SMA3.
New gene therapies and disease-modifying medications targeting the SMN1 and SMN2 genes, which increase production of SMN protein and reduce motor neuron loss, have helped improve prognosis.In May 2015, the U.S. Department of Health and Human Services (HHS) approved the addition of spinal muscular atrophy to the Recommended Uniform Screening Panel (RUSP) for newborns. This may help in early diagnosis and prompt treatment, which can be life-saving, especially with research of more effective medications underway.
What is the treatment for spinal muscular atrophy?
Treatment for spinal muscular atrophy depends on the severity of the disease and includes disease-modifying medications and treatment for symptoms and complications. Patients also have the option to enroll in clinical trials for new treatments.
The FDA has approved three disease-modifying medications to treat SMA caused by a missing or mutated SMN1 gene:
- Nusinersen sodium (Spinraza): Nusinersen is administered with an injection into the cerebrospinal fluid in the spinal canal. Nusinersen modifies the SMN2 gene to increase its production of functional SMN protein. Nusinersen is approved for use in children and adults.
- Onasemnogene abeparvovec-xioi (Zolgensma): Zolgensma is a gene replacement therapy administered with intravenous infusion. A non-infectious virus delivers a fully functional SMN1 gene into the motor neurons, which increases production of SMN protein. Zolgensma is a one-time therapy approved for children below 2 years of age.
- Risdiplam (Evrysdi): Risdiplam is an oral solution that modifies SMN2 gene to make it produce more functional SMN protein. Risdiplam is approved for children over 2 months of age and is a life-long treatment.
Symptom and complication therapies
Treatment to relieve symptoms and alleviate complications vary depending on the patient’s condition. Therapies may include:
- Breathing support and devices to remove respiratory secretions (if the patient has respiratory muscle weakness)
- Feeding tubes for weakness in the chewing and swallowing muscles
- Physical and occupational therapies
- Supportive aids such as back braces, leg braces, walkers or wheelchairs
- Surgery to treat hip dislocations, fractures or scoliosis
What is the life expectancy of someone with spinal muscular atrophy?
Life expectancy depends on the severity of the disease:
- Type 0: Babies with SMA type 0 have extremely weak respiratory muscles and many also have congenital heart defects. Type 0 babies rarely survive beyond 6 months.
- Type 1: The majority of children with SMA type 1 do not survive beyond the age of 2 because of respiratory issues. New treatments, however, have helped prolong the life of children with SMA1 and enabled them to sit and even walk.
- Type 2: Most children with SMA type 2 survive into adolescence or young adulthood. Current disease-modifying treatments help improve muscle function and quality of life in these children.
- Type 3: With appropriate care and treatment, most patients with SMA type 3 have a normal life span. Treatment can improve motor function and slow down progression of the disease.
- Type 4: Life expectancy is normal in people with SMA type 4 and most remain mobile and active throughout their lives. Treatment can slow down disease progression and prevent complications.
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