Originals: Introduction to SMA: What is SMA?

We are here with the 1st part of our SMA file, which we will prepare as a long series of articles. At the end of this file, we will try to answer everything from what is SMA to why SMA drugs are so expensive.


Introduction to SMA: What is SMA?

  • Chapter I. What is SMA?
  • SMA Chapter II Diagnosis
  • SMA Chapter III. Treatment Methods
  • SMA Chapter IV. Why are treatments so expensive?

Chapter I. What is SMA?

SMA or Spinal muscular atrophy, was first described in 1891 by Guido Werdnig, an Austrian doctor, in 2 siblings. However, the first definition of SMA was made in 1903. [2]. Spinal muscular atrophy, or SMA, can be described as muscle weakness and atrophy resulting from degeneration at the cellular level [1]. SMA is a rare disease in general. Its incidence is reported to be approximately 10 per 100,000 live births [3].

SMA has classifications and is classified by sma survival times classified as 4 grades [2-4]. These classification studies go back to 1991. Some different classifications are also available.

0. Prenatal Respiratory failure at birth Week
I. 0-6 months Never sit <1 year
II. <18 months Sit >25 year
III. >18 months Stand or ambulatory Adult
IV. 30 years Ambulatory Adult
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Table-1 SMA classifications [2-4]

SMA is clinically examined in 4 different types. SMA type 0 occurs before birth.

Type 0. It presents with severe malaise, hypotonia and respiratory distress at birth. Babies with SMA born with this type have severe respiratory distress. After 6 months, survival is rarely seen [4].

Type I. The patient group graded as SMA Type 1 shows symptoms in infants before 6 months of age. This group, which constitutes 60% of the patients diagnosed with SMA, can never sit without support. They usually do not survive beyond 2 years of age due to respiratory failure [3]. The characteristic soul-shaped chest leads to abdominal breathing [4].

Type II. It usually occurs between 6 and 12 months, while the onset of symptoms averages 8 months. While hand tremor is common, cognition is normal.

Type III. It typically occurs after 18 months, with an average onset occurring after 39 months. Legs are more severely affected than arms.

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Type IV. It typically manifests as muscle weakness in the 20s-30s [4].

The disease first manifests itself in various ways, depending on the age of onset of the disease. While severe hypotonia and feeding difficulties are observed especially in infants, the initial symptoms in young children can be seen as inability to climb stairs and falling frequently [6].

Hypotonia, which we will talk about frequently on SMA, is not the same thing as atrophy. Hypotonia is not necessarily directly related to muscle weakness. This is defined as the remaining tension in a muscle at rest.Hypotonia is usually present at birth and is often diagnosed in early infancy [5].

SMA and Genetics

SMA is most commonly caused by homozygous disruption on chromosome 5q on the SMN1 gene. It is called SMA5q. In addition, there have been treatment studies in the form of genetic modifications on SMN2 in recent years [7-8].

In addition, mutations on the IGHMBP2 protein of SMA Type 1 (SMARD1 or DSMA1) are thought to be effective on SMA. SMARD1 is called respiratory distress type 1. [9]

When we consider all SMA types, the gene and locus regions that are thought to affect SMA are listed below. [7]. All of these are covered in detail in Chapter 2.

  • SMN1
  • UBE1
  • SCO2
  • EXOSC3
  • TSEN54
  • RARS2
  • VRK1
  • DYNC1H1
  • BICD2
  • VAPB
  • LMNA
  • MAPT
  • AR
  • HSPB1/ HSPB8/ GARS/ DYNC1H1 (7q34)
  • HSPB8/ HSPB1/ HSPB3/ FBXO38 (11q13)
  • mtATP8
  • mtATP6
  • TRPV4
  • TRPV4
  • ATP7A
  • 9p21
  • SETX
  • DNAJB2; HSJ1
  • DCTN1
  • SLC5A7; CHT
  • BSCL2
  • REEP1
  • GARS

SMA Chapter II: Diagnosis


[1] Prior, Thomas W., et al. “Spinal Muscular Atrophy.” Nih.gov, University of Washington, Seattle, 3 Dec. 2020, www.ncbi.nlm.nih.gov/books/NBK1352/.

‌[2] Kolb, Stephen J., and John T. Kissel. “Spinal Muscular Atrophy: A Timely Review.” Archives of Neurology, vol. 68, no. 8, 2011, pp. 979–84, https://doi.org/10.1001/archneurol.2011.74.

[3] Verhaart, Ingrid E. C., et al. “Prevalence, Incidence and Carrier Frequency of 5q-Linked Spinal Muscular Atrophy – a Literature Review.” Orphanet Journal of Rare Diseases, vol. 12, no. 1, BioMed Central, 2017, p. 124, https://doi.org/10.1186/s13023-017-0671-8.

‌[4] Prior, Thomas W., et al. “Spinal Muscular Atrophy.” Nih.gov, University of Washington, Seattle, 3 Dec. 2020, www.ncbi.nlm.nih.gov/books/NBK1352/.

[5] Madhok, Sehajvir S., and Nadeem Shabbir. “Hypotonia.” Nih.gov, StatPearls Publishing, 2 May 2022, www.ncbi.nlm.nih.gov/books/NBK562209/.

[6] “Clinical Features, Epidemiology, Natural History, and Management of Spinal Muscular Atrophy.” Nih.gov, Canadian Agency for Drugs and Technologies in Health, 2018, www.ncbi.nlm.nih.gov/books/NBK533981/.

[7] Farrar, Michelle A., and Matthew C. Kiernan. “The Genetics of Spinal Muscular Atrophy: Progress and Challenges.” Neurotherapeutics : The Journal of the American Society for Experimental NeuroTherapeutics, vol. 12, no. 2, Springer US, 2015, pp. 290–302, https://doi.org/10.1007/s13311-014-0314-x.

[8] Jędrzejowska M. “Advances in Newborn Screening and Presymptomatic Diagnosis of Spinal Muscular Atrophy.” Degenerative Neurological and Neuromuscular Disease, vol. 10, Degener Neurol Neuromuscul Dis, 2020, https://doi.org/10.2147/DNND.S246907.

[9] Grohmann. “Mutations in the Gene Encoding Immunoglobulin Mu-Binding Protein 2 Cause Spinal Muscular Atrophy with Respiratory Distress Type 1.” Nature Genetics, vol. 29, no. 1, Nat Genet, 2022, https://doi.org/10.1038/ng703.

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