Spinal muscular atrophy (SMA) is an inherited autosomal recessive neurodegenerative disease. It is characterized by the loss of specialized nerve cells called motor neurons in the spinal cord and in the part of the brain that is connected to the spinal cord (the brain stem), leading to progressive muscle weakness.

Motor neurons control voluntary muscle movement, including those of the arms, legs, chest, face, throat and tongue. The loss of motor neurons leads to weakness and atrophy in these muscles. Fundamental activities using muscles, such as walking, sitting up, controlling head movement, breathing and swallowing, can be affected by the disease. Movement progressively becomes slower and over time, and the ability to control voluntary movement may be lost completely.

The disease is divided into subtypes based on the age of onset and maximum function achieved. SMA types 0, 1, 2, 3 and 4 are associated with mutations in the SMN1 gene, which is located on chromosome 5. This gene encodes for the SMN protein that is important for the survival of motor neurons. Some people have extra copies of a second gene called the SMN2 gene and the number of copies of this second gene can modify the course of SMA (types 2, 3 and 4). The more copies there are, the less severe the symptoms are.

Other types of SMA not linked to mutations in the SMN1 gene include, Finkel type SMASMA with respiratory distress syndrome (SMARD1)SMA lower extremity, dominant (SMA-LED), and X-linked SMA, also called Kennedy’s disease.

Finkel type SMA is associated with mutations in the VAPB gene. SMARD1 is a type of SMA that affects infants. SMA-LED affects lower extremities and is associated with mutations in the DYNC1H1 gene. X-linked SMA is a rare type of SMA caused by mutations in the UBA1 gene situated on the X chromosome. Symptoms of this type of SMA vary and include weakness and atrophy of the facial, jaw and tongue muscles, leading to difficulties in swallowing and changes in speech.

SMA symptoms

Some of the common symptoms of SMA include:

  • Poor muscle tone that leads to lack of motor development;
  • Breathing difficulties that may lead to respiratory complications, including underdeveloped lungs and weak cough;
  • Scoliosis, or an abnormal spinal curvature, due to weakness of the muscles that normally support the spinal column.

SMA diagnosis

SMA diagnosis may start with a physical examination by a physician who will record your family history. The doctor also may want to check the level of creatine kinase (CK) in your blood. CK is an enzyme that leaks out of muscles as they deteriorate. Although this is not an SMA-specific test, high CK levels indicate that muscles have been damaged.

When symptoms are present, diagnosis can be made through genetic testing, as different forms of SMA are linked to mutations in specific genes (e.g., SMA types 0 to 4 are linked to mutations in the SMN1 gene, and Finkel type SMA to the VAPB gene mutation). Having extra copies of the SMN2 gene can modify the course of SMA (types 2, 3 and 4). The more SMN2 gene copies there are, the less severe the symptoms.

In situations where it is not possible to conduct SMN gene tests or no abnormalities are identified, other tests may be conducted. These include electromyography and muscle biopsy.

Electromyography assesses the health of the muscles and motor neurons that control them. This test determines whether muscles are responding to electrical stimulations.

In a muscle biopsy, a small section of muscle tissue from the upper thigh is removed and examined to see if it is degenerating or has characteristics unique to SMA type 1 and 2.

SMA treatments

SMA has no cure yet, and existing treatments consist of managing the symptoms and preventing complications. These include:

  • Palliative care aims to improve the quality of life of both the patient and their family, focusing on relief from the symptoms and stress caused by the disease.
  • Physical therapy and rehabilitation may help to improve posture, prevent joint immobility and slow muscle weakness and atrophy in some forms of SMA.

The only treatment addressing the underlying genetic cause of SMA is Spinraza (nusinersen), which was approved by the U.S. Food and Drug Administration (FDA) in December 2016. The therapy aims to increase the production of SMN protein from the SMN2 gene.

Additionally, there are a number of experimental therapies being tested to treat SMA.

Note: SMA News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.