Spinal Muscular Atrophy (SMA) is an inherited disease that affects nerves and muscles, causing them to become progressively weaker. It mostly affects infants and children, but can also develop in adults. Symptoms and disease course vary depending on the type of SMA. Gene replacement therapies have been a new hope in the fight against the disease in recent years.
Spinal Muscular Atrophy (SMA) is a genetic (inherited) neuromuscular disease in which muscles weaken and atrophy. People with SMA lose motor neurons (a type of nerve cell) in the spinal cord that control muscle movement. Without these motor neurons, the muscles cannot receive the nerve signals that move the muscles. The word atrophy is a medical term that means “to waste away”. In SMA, some muscles become smaller and weaker because they are no longer used.
According to the SMA Clinical Protocol published by the Ministry of Health, there are approximately 3,000 children and adults living with SMA in Turkey and an average of 150 babies are born with SMA annually. SMA is a disease that affects one in every 6,000 to 10,000 children worldwide. The incidence is quite high in Turkey.
A person with SMA inherits two copies of a missing or defective (mutated) motor neuron 1 (SMN1) gene. One defective gene comes from the mother and the other from the father. An adult may unknowingly have only one copy of the defective gene that causes SMA. Worldwide, between 1/47 -1/90 adults carry the mutated SMN1 gene. These carriers have one healthy SMN1 gene and one missing or defective SMN1 gene. Carriers do not develop SMA. Two carriers have a 1 in 4 chance of having a child with SMA.
Type 1 (severe): About 60% of people with SMA have type 1, also called Werdnig-Hoffman disease. Symptoms appear at birth or in the first six months of a baby’s life. Babies with SMA type 1 have difficulty swallowing and sucking. They do not reach typical milestones, such as holding their head up or sitting up. As muscles weaken, babies become more susceptible to respiratory infections and collapsed lungs (pneumothorax). Most children with SMA type 1 die before their second birthday.
Type 2 (intermediate): Symptoms of type 2 SMA (also called Dubowitz disease) appear when a child is six to 18 months old. This type usually affects the lower limbs. Children with SMA type 2 can sit up but cannot walk. Most children with SMA type 2 live into adulthood.
Type 3 (mild): SMA type 3 symptoms (also called Kugelbert-Welander or juvenile SMA) appear after the first 18 months of a child’s life. Some people with type 3 do not show signs of the disease until early adulthood. Type 3 symptoms include mild muscle weakness, difficulty walking and frequent respiratory infections. Over time, symptoms can affect the ability to walk or stand. SMA type 3 does not significantly shorten life expectancy.
Type 4 (adult): The rare adult form of SMA typically does not appear until the mid-30s. Symptoms of muscle weakness progress slowly, so most people with type 4 remain active and live their lives to the fullest.
People with SMA either do not have part of the SMN1 gene or have an altered (mutated) gene. A healthy SMN1 gene produces the SMN protein. Motor neurons need this protein to survive and function properly. People with SMA do not produce enough SMN protein, so motor neurons shrink and die. As a result, the brain cannot control voluntary movements, especially in the head, neck, arms and legs. There are also people with SMN2 genes that produce small amounts of SMN protein. A person can have up to eight copies of an SMN2 gene. Multiple copies of the SMN2 gene usually cause less severe SMA symptoms because the extra genes make up for the missing SMN1 protein. In rare cases, mutations of non-SMN genes (non-chromosome 5) cause SMA.
Symptoms of SMA vary depending on the type. In general, people with SMA suffer from a progressive loss of muscle control, movement and strength. Muscle loss worsens with age. Usually the muscles closest to the trunk and neck are most affected by the disease. Some people with SMA will never be able to walk, sit or stand. Others gradually lose their ability to perform these actions.
Some SMA symptoms are similar to those seen in neuromuscular disorders such as muscular dystrophy. To find the cause of the symptoms, your doctor will perform a physical examination and take a medical history. Your doctor may also order one or more of the following tests to diagnose SMA:
Blood test: An enzyme and protein test in the blood can detect high levels of creatine kinase. This enzyme is released into the bloodstream when muscle atrophy occurs.
Genetic testing:This blood test can detect problems with the SMN1 gene. As a diagnostic tool, genetic testing is 95% effective in finding the altered SMN1 gene. In our country, SMA testing is also performed as part of routine newborn screening.
Nerve conduction test:An electromyogram (EMG) measures the electrical activity of muscles and nerves.
Muscle biopsy: In rare cases, a physician may perform a muscle biopsy. In this procedure, a small amount of muscle tissue is removed and sent to a laboratory for testing. A biopsy can detect atrophy or muscle loss.
If you are pregnant and have a family history of SMA, prenatal tests can determine whether your unborn child has the disease. These tests slightly increase the risk of miscarriage or abortion. Prenatal tests for SMA include:
Amniocentesis During amniocentesis, your gynecologist inserts a thin needle into your abdomen to remove a small amount of amniotic fluid from the amniotic sac. A laboratory specialist (pathologist) tests the fluid for SMA. This test is done after the 14th week of pregnancy.
There is no cure for SMA. Treatments depend on the type of SMA and symptoms. Many people with SMA benefit from physical therapy, occupational therapy and assistive devices such as orthopedic braces, crutches, walkers and wheelchairs. These treatments can also help:
Treatment to slow the course of the disease: These drugs stimulate the production of the SMN protein. Nusinersen (Spinraza®), which is also covered by the state in Turkey, is for children aged 2 to 12 years. Your doctor injects the medicine into the space around the spinal canal. Another medicine, Risdaplam (Evrysdi®), helps adults and children older than two months. Risdaplam is taken by mouth (orally) daily.
Gene replacement therapy: Recent studies have shown high benefit from a single intravenous (IV) infusion of a drug called Onasemnogene abeparvovec-xioi (Zolgensma®). This therapy replaces a missing or defective SMN1 gene with a functioning gene. It has not yet been included in the protocol in Turkey.
Over time, people with SMA experience progressive muscle weakness and loss of muscle control. Possible complications include:Bone fractures, hip dislocations and scoliosis (curvature of the spine). Malnutrition and dehydration due to eating and swallowing problems that may require a feeding tube. Pneumonia and respiratory infections. Weak lungs and respiratory problems that may require respiratory support (ventilation).
SMA is an inherited disease. If you or your partner carry the mutated gene that causes SMA, a genetic counselor can explain the risk of your child having SMA or being a carrier. You can take steps before you get pregnant to reduce the risk of developing SMA. A procedure called preimplantation genetic diagnosis (PGD) identifies embryos that do not carry the mutated gene. Your doctor implants healthy embryos during in vitro fertilization (IVF). PGD ensures that your child will have two healthy SMN1 genes and will not develop SMA.