Spinal muscular atrophy (SMA) type 1 is a genetic condition in which the nerves that control movement, breathing, and swallowing become progressively weaker and smaller.
SMA has five types with symptoms that vary in severity. The types tend to present at different age ranges. In the United States, fewer than 5,000 people have SMA type 1, which typically affects infants.
This article focuses on SMA type 1, which goes by several other names, including:
- muscular atrophy, infantile
- proximal spinal muscular atrophy type 1
- SMA type 1, SMA-I, or SMA1
- SMA, infantile acute form
- Werdnig Hoffmann disease
Read on to learn more about the symptoms, causes, risk factors, diagnosis, treatment, and outlook for SMA type 1.
Symptoms of SMA type 1 may vary but typically include:
- progressive muscle weakness, particularly in the hips, thighs, shoulders, and upper back
- hypotonia, or low muscle tone
- difficulties with feeding and suckling
- a weak cry
- involuntary twitching of the tongue
- lack of reflexes
- atypical breathing
- a pear-shaped body
Symptoms of SMA type 1 rarely develop later in life. Most symptoms become obvious at birth or within the first 23 months of life. Infants with SMA type 1 tend to develop symptoms at birth or before 6 months of age.
SMA type 1 is a genetic condition resulting from genetic mutations or faulty genes. Infants with SMA type 1 inherit the disease from their parents.
Most people with SMA type 1 have mutations, atypical changes, or deletions of a chromosome 5 gene protein known as SMN1 or survival motor neuron. To have SMA type 1, someone must have an atypical mutation or deletion on both copies of their SMN1 gene.
In rare cases, changes in other genes or chromosomes may cause SMA.
The only risk factor for developing SMA type 1 is having parents who carry an atypical or faulty SMN1 gene protein.
Many people who have SMA or are carriers of it have significant deletions in the region of chromosome 5 known as exon 7.
To diagnose SMA type 1, a doctor will do a physical exam. They will also ask the infant’s caregivers to describe any symptoms, including when they first appeared and how they have progressed.
To confirm a diagnosis of SMA type 1, a doctor will draw a blood sample from the infant and send it to a lab to test for a faulty or atypical SMN1 gene.
In rare cases, a doctor may also perform a muscle biopsy. This means they will take a small sample of muscle, usually from the thigh, and send it to a lab for evaluation.
Another test doctors sometimes use to help diagnose SMA type 1 is a nerve conduction test, which involves using an electromyogram to measure muscular electrical activity.
Experts recommend SMA testing as part of standard newborn screening tests.
In the past, treatment for SMA focused on reducing the impact or severity of symptoms and improving quality of life.
Common supportive treatments for SMA include:
- ventilation devices to help with breathing
- nutritional monitoring to reduce the risk of malnourishment
- feeding tubes
- back braces or spine-straightening surgery
- creatine or coenzyme Q10 supplements
- physical therapy
However, since 2016, the treatments available for SMA have started to focus on slowing the progression of the disease or reversing its course.
The first medication that the Food and Drug Administration (FDA) approved to treat SMA is Spinraza (nusinersen). It is a disease-modifying treatment that targets atypical or faulty SMN1 gene proteins.
Treatment involves injecting the drug into the spinal canal or the subarachnoid space. Spinraza is suitable for children between 2 and 12 years of age. It may help children with SMA live longer and improve their quality of life.
In some cases, the treatments may completely stop the progression of SMA and reverse the symptoms.
Another medication, Zolgensma (onasemnogene abeparvovec-xioi), is the first FDA-approved gene replacement therapy for treating a neuromuscular disease. It is effective in infants under 2 years of age.
Zolgensma treatment involves a one-time intravenous infusion that delivers healthy SMN1 gene proteins to cells.
Additionally, in summer 2020, the FDA approved Evrysdi (risdiplam) for treating SMA in infants older than 2 months. This oral medication increases levels of SMN proteins by increasing the production of the SMN1 “backup” gene, SMN2.
In the past, most infants with SMA did not survive past age 2. Doctors made life expectancy estimates based on the age at which symptoms began and the amount of healthy SMN protein present.
However, most medical professionals no longer base life expectancy on this information.
In recent years, disease-modifying or gene replacement therapies have greatly extended the life expectancy of people with SMA.
Aside from SMA type 1, the other four types of SMN-related SMA are:
- SMA type 0: Severe symptoms are present during pregnancy. Life expectancy is between 1 and 6 months.
- SMA type 2: SMA type 2 is also known as intermediate SMA or Dubowitz disease. Symptom onset occurs between 3 and 15 months of age. Life expectancy varies.
- SMA types 3 and 4: These types are also known as late onset SMA, mild SMA, juvenile or adult onset SMA, or Kugelberg-Welander disease. Symptoms usually develop sometime between 18 months of age and adulthood. SMA type 4 symptoms tend to develop in people over 30. People with SMA type 4 have a typical life expectancy.
Some types of SMA, such as spinal muscular atrophy with respiratory distress, are not related to SMN1.
Spinal muscular atrophy type 1 (SMA type 1) is the most common form of SMA in infants, accounting for about 60% of cases. Without treatment, infants with SMA type 1 tend to develop severe symptoms before 6 months of age and die before reaching age 2.
Infants with SMA type 1 typically cannot sit on their own or reach other motor-related developmental milestones.
Newer treatment options, such as disease-modifying medications and gene replacement therapy, may extend the life expectancy of infants with SMA type 1.