IllnessSpinale Muskelatrophie; SMN1-/SMN2-Gene

SP6755_DH

Disease information

Spinal muscular atrophy (SMA) is one of the most frequent autosomal recessively inherited diseases in Europe, the most severe course leads to early infantile death. The frequency of heterozygous carriers is 1/40 tos 1/60 for the European population. In cultures with high rates of consanguinity autosomal recessive diseases such as SMA observed often (1). The majority of affected children has lost both SMN1 gene copies as cause of disease. Hence the parents are mostly carriers of one lost SMN1 gene copy, i.e. only for one allele. The different courses of the SMA forms I to III and the varying age of onset are mainly determined by the copy number of the virtually identical SMN2 genes neighboring on the same chromosome. From the SMN2 gene only a small amount of full-length transcripts are produced (2, 3). - Several gene therapeutich approaches have been established oon this basis, like e.g. Nusinersen (SpinrazaTM). This medication increases as antisense oligonucleotid the production of the SMN transcript by improved splicing of the SMN2 mRNA, thus working exclusively if there are several copies of the SMN2 gene (4). Onasemnogene Abeparvovec (ZolgensmaTM) is a Adeno-associated virus 9 based gene therapy with which a transgene copy of the SMN1 gene is transfected, that codes for the SMN protein (5).

References: (1) Shafeghati Y et al. Arch Iranian Med. 7(1): 47 – 52; 2004. (2) Prior, TW et al.; Genet Med. 2011 Jul;13(7):686-94. (3) Prior, TW and Finanger, E; online Gene Reviews http://www.ncbi.nlm.nih.gov/books/NBK1352/. (4) Ottensen. Transl Neurosci. 2017; 8: 1–6. (5) Hoy SM. Onasemnogene Abeparvovec: First Global Approval. Drugs. 2019 Jul;79(11):1255-1262.

ORPHA:83330 Proximal spinal muscular atrophy type 1; ORPHA:83418 SMA type 2; ORPHA:83419 SMA type 3; ORPHA:83420 SMA type 4

ORPHA:83330 Proximal spinal muscular atrophy type 1

Severe infantile form: progressive muscle weakness + hypotonia resulting from degeneration/loss of the lower motor neurons in spinal cord + brain stem nuclei

ORPHA:83418 SMA type 2

Prevalence: 1-9/100 000 (prevalence 1/70 000, slightly more frequent in males than females)

Chronic infantile form: muscle weakness + hypotonia resulting from degeneration/loss of lower motor neurons in the spinal cord + brain stem nuclei

ORPHA:83419 SMA type 3

Prevalence: 1-9/1 000 000 (1/375000)

Relatively mild form: muscle weakness + hypotonia resulting from degeneration/loss of lower motor neurons in the spinal cord + brain stem nuclei

ORPHA:83420 SMA type 4

Adult-onset form: muscle weakness + hypotonia resulting from the degeneration/loss of lower motor neurons in the spinal cord + brain stem nuclei

• Alias: Infantile spinal muscular atrophy
• Alias: Proximal spinal muscular atrophy type 0, 1-4
• Alias: Spinal muscular atrophy-0, -1-4 [SMA]
• Alias: Werdnig-Hoffmann disease
• Spinal muscular atrophy, type 0 [prenatal] (SMN1)
• Spinal muscular atrophy, type III, modifier of (SMN2)
• Spinal muscular atrophy-1 (SMN1)
• Spinal muscular atrophy-2 (SMN1)
• Spinal muscular atrophy-3 (SMN1)
• Spinal muscular atrophy-4 (SMN1)