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LOOK OUT FOR EARLY WARNING SIGNS OF SPINAL MUSCULAR ATROPHY (SMA)1–3

LOOK OUT FOR EARLY WARNING SIGNS OF SPINAL MUSCULAR ATROPHY (SMA)1–3

REFER FOR DIAGNOSIS

For babies with SMA fast diagnosis is vital. This is because any lower motor neuron damage occurring before treatment is irreversible4,5

What is SMA?

SMA is a rare, progressive, inherited monogenic disease, characterized by lower motor neuron degeneration and muscle weakness6–10

Untreated, SMA is the 2nd most common fatal autosomal recessive disorder after cystic fibrosis11

SMA remains the leading genetic cause of infant mortality in the absence of therapeutic intervention5,10

SMA is typically classified into 4 phenotypes (Types 1–4) that range in severity. SMA Types 1 and 2 are the most severe and common forms with onset between birth and 18 months3,5,10

SMA affects approximately 1 in 10,000 – 12,000 live births and can impact any race or sex6,12

Around 1 in 50 people are carriers of the disease mutation13

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Cause of SMA

SMA is caused by an absent or dysfunctional survival motor neuron 1 (SMN1) gene14–18

The body has a back-up gene, SMN2, however, it is only capable of producing a small amount of functional SMN protein, which is insufficient for motor neuron survival and function6,14,15,17,18

Click to see the difference:

Unaffected individual:

  • SMN protein is critical for neuronal survival and neuromuscular junction formation15

  • SMN1 is the primary gene that encodes SMN protein with SMN2 as a back-up15,19

Functional SMN protein

Non-functional SMN protein

Functional SMN protein

Non-functional SMN protein

Affected individual:

  • SMN1 gene is absent or dysfunctional14–17

  • SMN2 alone is unable to produce sufficient SMN protein6,14,15,18

  • SMN protein deficiency leads to irreversible neuronal degeneration and loss of muscle function in SMA5,14,15

Functional SMN protein

Non-functional SMN protein

Functional SMN protein

Non-functional SMN protein

STOPPING NEURONAL LOSS

Loss of motor neurons in SMA is irreversible4,5

Disease progression

More than 90% of untreated patients with SMA Type 1 will not survive or will need permanent ventilatory support by 2 years of age20

Every delay in the diagnosis of SMA Type 1 can jeopardize lower motor neuron survival,4 directly impacting neuromuscular function21

Your rapid referral is crucial to halt or delay disease progression, and enable your patient access to the best available care4,10,22

PNCR: SMA Type 1 survival rates*

NeuroNext: SMA Type 1 survival rates*

PNCR, Pediatric Neuromuscular Clinical Research

*Event-free survival for PNCR = no death, and no need for ≥16 hours/day ventilation continuously for 14 days, in the absence of an acute reversible illness;20 n=23 (Type 1 patients with 2 copies of SMN2). Survival for NeuroNext = no death, or no intubation; n=2021

Adapted from Anderton RS and Mastaglia FL. 201515, Finkel RS. 201324, Finkel RS, et al. 201420 and Kolb SJ, et al. 201721

Disease progression

While patients diagnosed with SMA Type 2 (with disease onset between 6–18 months of age) may possibly reach motor milestones in the first years of life, all patients will show a clear and progressive decline with long-term follow-up8

Every delay in the diagnosis of SMA can jeopardize lower motor neuron survival,4 directly impacting neuromuscular function4,10,22

Your rapid referral is crucial to halt or delay disease progression, and enable your patient access to the best available care4,10,22

TIMPSI: Average Test of Infant Motor Performance Screening Items

Adapted from Kolb SJ, et al. 201721

IMPORTANCE OF EARLY DIAGNOSIS

Fast diagnosis of SMA is vital, as damage that occurs before treatment is irreversible4,5

Early diagnosis of SMA is critical to:25–27

  • Begin optimal therapeutic intervention and management strategies

  • Relieve the stress and burden experienced by patients and caregivers

Research suggests early medical intervention provides the most benefit in SMA10,22,28

Adapted from Serra-Juhe C and Tizzano EF, 201919

Your early action could limit the irreversible damage associated with SMA4,5,10,29

References

NMD, Neuromuscular disease.

References
  • 1. Kolb SJ and Kissel JT. Neurol Clin. 2015;33(4):831–46.
  • 2. Prior TW, Leach ME, Finanger E. Spinal Muscular Atrophy. 2000 Feb 24 [Updated 2019 Nov 14]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2020.
  • 3. Wang CH, et al. J Child Neurol. 2007;22(8):1027–49.
  • 4. Govoni A, et al. Mol Neurobiol. 2018;55(8):6307–18.
  • 5. Glascock J, et al. J Neuromuscul Dis. 2018;5(2):145–58.
  • 6. Verhaart IEC, et al. Orphanet J Rare Dis. 2017;12:124.
  • 7. Richter T, et al. Value Health. 2015;18(6):906–14.
  • 8. Mercuri E, et al. Neurology. 2019;93(13):e1241–7.
  • 9. Mercuri E, et al. Orphanet J Rare Dis. 2020;15(1):84.
  • 10. Schorling DC, et al. J Neuromuscl Dis. 2020;7:1–13.
  • 11. D’Amico A, et al. Orphanet J Rare Dis. 2011;6:71.
  • 12. Cure SMA (2023). About SMA. Available at: https://www.curesma.org/about/. Date accessed: July 2023.
  • 13. Verhaart IEC, et al. Additional file 2: Table S1. Overview carrier frequencies of SMA. Supplementary material to Verhaart IEC, et al. Orphanet J Rare Dis. 2017;12:124. Available at: https://ojrd.biomedcentral.com/articles/10.1186/s13023-017-0671-8. Date accessed: July 2023.
  • 14. Coovert DD, et al. Hum Mol Genet. 1997;6(8):1205–14.
  • 15. Anderton RS and Mastaglia FL. Expert Rev Neurother. 2015;15(8):895–908.
  • 16. Lefebvre S, et al. Cell. 1995;80:155–65.
  • 17. National Institute for Health (NIH) (2020a). Genetics home reference. Your guide to understanding genetic conditions. SMN1 gene. Available at: https://ghr.nlm.nih.gov/gene/SMN1. Date accessed: July 2023.
  • 18. NIH (2020b). Genetics home reference. Your guide to understanding genetic conditions. SMN2 gene. Available at: https://ghr.nlm.nih.gov/gene/SMN2. Date accessed: July 2023.
  • 19. Serra-Juhe C and Tizzano EF. Eur J Hum Genet. 2019;27(12):1774–82.
  • 20. Finkel RS, et al. Neurology. 2014;83(9):810–7.
  • 21. Kolb SJ, et al. Ann Neurol. 2017;82(6):883–91.
  • 22. Kirschner J, et al. Eur J Paediatr Neurol. 2020;28:38–43. Published online ahead of print.
  • 23. Swoboda KJ, et al. Ann Neurol. 2005;57(5):704–12.
  • 24. Finkel RS. Neuromuscul Disord. 2013;23(2):112–5.
  • 25. Qian Y, et al. BMC Neurol. 2015;15:217.
  • 26. Mammas IN and Spandidos DA. Exp Ther Med. 2018;15:3673–9.
  • 27. Lurio JG, et al. Am Fam Physician. 2015;91(1):38–44.
  • 28. Waldrop MA and Elsheikh BH. Neurol Clin. 2020;38(3):505–18.
  • 29. Lowes LP, et al. Pediatr Neurol. 2019;98:39–45.