August is typically one of the hottest months of the year, so this is an excellent time to stay indoors in the air conditioning and read a blog. The topic of this one is spinal muscular atrophy, or SMA, a genetic disorder that primarily affects infants and children.

August is Spinal Muscular Atrophy Awareness Month.

SMA is a neuromuscular disorder. It’s a progressive disease that destroys the nerve cells that control muscle movement, called motor neurons. With SMA, motor neurons in the spinal cord are affected. As a result, the muscles begin to waste away, or atrophy. Over time, this takes away the ability to walk, eat and breathe.

Approximately one in every 6,000 to 10,000 babies worldwide is born with SMA. Estimates suggest that 10,000 to 25,000 children and adults in the US are living with SMA, making it one of the most common rare diseases. It is estimated that about 6 million Americans are carriers of the mutated gene that leads to SMA. That’s nearly one in every 50 people.

In almost all cases, SMA is caused by the insufficient production of a protein necessary for proper motor neuron function called survival motor neuron (SMN) protein. The SMN protein is primarily produced by the SMN1 gene located on chromosome 5. The SMN2 gene also produces the SMN protein but in smaller quantities.

In children who have SMA, both SMN1 genes are mutated or missing, and their SMN2 genes don’t make enough survival motor neuron to compensate. Without adequate SMN proteins, the motor neurons in the spinal cord begin to wither and die, leading to debilitating and sometimes fatal muscle weakness.

Some forms of SMA are not linked to SMN1, chromosome 5 or SMN protein deficiency. These vary greatly in severity and the muscles affected. SMN-related SMA primarily affects the proximal muscles, those closest to the center of the body. Other forms primarily affect the distal muscles, those farthest away from the body’s center.

SMA is inherited in an autosomal recessive pattern, which means that both copies of the SMN1 gene in each cell must be mutated. To inherit SMA, both parents must carry the mutated gene and pass it along to their child. When both parents are carriers of the mutated gene, a child has a 25 percent chance of being born with SMA.

In SMN-related SMA, there is wide variability in age of onset, symptoms and rate of progression. To account for the differences, SMA is typically classified into four types. The age at which SMA symptoms begin roughly correlates with the degree to which motor neuron function is affected. In general, the earlier the age of onset, the greater the impact on function.

Type 1 SMA, also called Werdnig-Hoffmann disease, affects about 60 percent of people with SMA. It is a severe form with muscle weakness evident at birth or within the first few months. Most children with type 1 SMA cannot control their head movements or sit without help. They often have swallowing problems, which cause feeding difficulties that ultimately impair growth. They also experience breathing problems.

Most children with type I SMA don’t survive past early childhood due to respiratory failure. However, with more proactive care and newer treatments, children with this disorder are living longer and reaching higher milestones, such as sitting up and even walking.

Children with type 2, or Dubowitz disease, develop muscle weakness between the ages of 6 and 12 months. While those with this type can often sit on their own, they typically cannot stand or walk unaided. They often have tremors, scoliosis and respiratory muscle weakness that can be life-threatening. Still, children with type 2 SMA can live into their 30s.

Type 3 SMA, also called Kugelberg-Welander disease, is a mild form of the condition. Symptoms can appear anywhere from 18 months to early adulthood. Those with this type learn to stand and walk, but often lose these abilities later in life. They generally experience mild muscle weakness and are at high risk for respiratory infections. Most people with this type have near normal life expectancies.

Type 4, or adult-onset SMA, is rare, accounting for less that 5 percent of all cases. It generally does not present until people are in their 20s or 30s. People with this type can walk throughout life, but typically experience mild to moderate muscle weakness, tremors and mild breathing problems. People with type 4 SMA have a normal life expectancy.

SMA is typically diagnosed using a blood test that looks for the mutated SMN1 gene. The doctor will recommend this blood test if your child’s symptoms and diagnostic workup suggest SMA. The doctor may also order an electrical study called electromyography (EMG) or a muscle biopsy to rule out other disorders and confirm the SMA diagnosis.

In July 2018, SMA screening was added to the Recommended Uniform Screening Panel for newborns. This helps ensure that every baby is screened, which permits early access to life-changing and even life-saving interventions.

There is no cure for SMA. Treatment focuses on easing symptoms, preventing complications and improving quality of life. Therapies are based on the type of SMA, the severity of the condition and the child’s age. They can range from feeding and breathing tubes to orthopedic braces, wheelchairs, and physical and occupational therapy.

Medications that stimulate the production of the SMN protein are also available to treat SMA. These medications are called disease-modifying therapies.

In December 2016, nusinersen (SPINRAZA®) was approved by the Food and Drug Administration for treating all four types of SMN-related SMA in children and adults. SPINRAZA may be effective at slowing, stopping or possibly reversing SMA symptoms.

In May 2019, the FDA approved ZOLGENSMA®, the first gene replacement therapy for a neuromuscular disease such as SMA.

In August 2020, the FDA approved risdiplam (Evrysdi®) for the treatment of SMA in ages 2 months and older. Evrysdi is an oral medication designed to increase the amount of SMN protein by boosting its production by the SMN2 genes. Research is ongoing for additional disease-modifying therapies for SMA.

Patti DiPanfilo