Özge’s background is in research; she holds a MSc. in Molecular Genetics from the University of Leicester and a PhD. in Developmental Biology from the University of London. Özge worked as a bench scientist for six years in the field of neuroscience before embarking on a career in science communication. She worked as the research communication officer at MDUK, a UK-based charity that supports people living with muscle-wasting conditions, and then a research columnist and the managing editor of resource pages at BioNews Services before joining Rare Disease Advisor.
SMA Type 1
Spinal muscular atrophy (SMA) type 1 is the most common type of SMA and the most severe form of the disease after SMA type 0.1 The disease is sometimes referred to as Werdnig-Hoffmann disease, infantile spinal muscular atrophy type 1, or floppy baby syndrome.2
SMA Type 1 Causes
SMA type 1 is caused by mutations in the SMN1 gene. This gene contains the information necessary for cells to make a protein that is essential for the survival of motor neurons.
When there is a mutation in the SMN1 gene, cells cannot make enough SMN protein, which leads to the death of motor neurons. This means that no signals are coming from motor neurons to the muscle, causing them to atrophy and die over time and causing muscle weakness and floppiness.
Patients with SMA type 1 only have 2 to 3copies of a second gene, SMN2, from which some functional SMN protein can be produced.3 However, SMN production is not sufficient in these patients and, as a result, the symptoms of SMA type 1 are severe.
SMA type 1, like the other types of SMA caused by mutations in the SMN1 gene, is inherited in an autosomal recessive manner.4 This means that a baby must inherit 2 faulty copies of the SMN1 gene, one from each parent, to develop SMA.
SMA Type 1 Symptoms
Babies born with SMA type 1 show symptoms within the first 6 months of life.5 These include hypotonia or low muscle tone and breathing and swallowing difficulties. Affected infants cannot lift their heads or sit without support. Frequent chest infections and aspiration pneumonia due to respiratory muscle weakness are common.6
SMA type 1 does not affect intelligence. Babies can frown and smile, as their facial muscles are usually not affected.6
SMA Type 1 Diagnosis
The optimal diagnostic approach for SMA type 1 is through genetic testing that looks for mutations in the SMN1 gene.7 However, genetic testing of the SMN1 gene alone is not able to differentiate between the different types of SMA linked to chromosome 5. Instead, the disease is classified according to the age of onset of the symptoms. If a patient has a mutation in the SMN1 gene and symptoms appear before the age of 6 months, they are diagnosed with SMA type 1.
Because some treatments are most effective before symptoms develop, it is of great importance to diagnose the disease as early as possible. Newborn screening, therefore, plays an essential role in the early diagnosis of SMA. This way, the disease can be diagnosed at birth or soon after and early treatment can be given. In the US, SMA is included in newborn screening programs in 34 states.8
SMA Type 1 Treatment
Until recently, treatment approaches focused primarily on reducing the symptoms of SMA type 1 and improving patients’ quality of life.6
For example, infants affected by the disease may benefit from feeding tubes where food can be directly delivered into the stomach or intestines. This can help them obtain all the nutrition they need and gain weight as they grow.
Respiratory assistance through ventilators can also help with breathing difficulties. Some infants and children with the disease may benefit from physiotherapy, which can help maintain muscle strength and range of motion.
Currently, there are 3 treatments that address the underlying cause of SMA. These are nusinersen (Spinraza),9 onasemnogene abeparvovec-xioi (Zolgensma),10 and risdiplam (Evrysdi).11
Nusinersen and risdiplam aim to increase the production of functional SMN protein from the SMN2 gene while onasemnogene abeparvovec delivers a healthy copy of the SMN1 gene to the patient’s body using a viral vector.
All 3 treatments have been approved by the US Food and Drug Administration (FDA) to treat all types of SMA, including SMA type 1. Onasemnogene abeparvovec is approved to treat patients up to age 2, while risdiplam is approved for patients aged 2 years and older. Nusinersen can be used in patients with SMA types 1, 2, or 3 of any age.
Both nusinersen and risdiplam are life-long treatments while onasemnogene abeparvove is a one-off infusion into the bloodstream. Nusinersen must be administered intrathecally every 4 months after a series of loading doses. Risdiplam is available as a liquid solution and parents or caregivers can administer the treatment by mouth or feeding tube.
Reviewed by Michael Sapko, MD, on 7/1/2021
- Spinal muscular atrophy. Medline Plus. Accessed May 25, 2021.
- SMN1 gene. Medline Plus. Accessed May 25, 2021.
- Butchbach MER. Copy number variations in the survival motor neuron genes: implications for spinal muscular atrophy and other neurodegenerative diseases. Front Mol Biosci. 2016;3:7. doi:10.3389/fmolb.2016.00007
- About spinal muscular atrophy. National Human Genome Research Institute. Accessed May 25, 2021.
- Types: spinal muscular atrophy. NHS. Accessed May 25, 2021.
- Type 1. SMA Europe. Accessed May 25, 2021.
- Prior TW, Leach ME, Finanger E. Spinal muscular atrophy. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews. University of Washington; 2000. Updated December 3, 2020. Accessed May 25, 2021.
- Newborn screening for SMA. Cure SMA. Accessed May 25, 2021.
- Spinraza. European Medicines Agency. Updated November 2017. Accessed May 25, 2021.
- Zolgensma – one-time gene therapy for spinal muscular atrophy. Med Lett Drugs Ther. 2019;29;61(1577):113-114.
- Evrysdi. Cure SMA. Accessed May 25, 2021.