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Review
. 2024 Mar 31;43(1):1-7.
doi: 10.36185/2532-1900-402. eCollection 2024.

Fatigue in Spinal Muscular Atrophy: a fundamental open issue

Oscar Crisafulli  1 , Angela Berardinelli  2 , Giuseppe D'Antona  1   3
Affiliations
Review

Fatigue in Spinal Muscular Atrophy: a fundamental open issue

Oscar Crisafulli et al. Acta Myol. .

Abstract

Hereditary proximal 5q Spinal Muscular Atrophy (SMA) is a severe neuromuscular disorder with onset mainly in infancy or childhood. The underlying pathogenic mechanism is the loss of alpha motor neurons in the anterior horns of spine, due to deficiency of the survival motor neuron (SMN) protein as a consequence of the deletion of the SMN1 gene. Clinically, SMA is characterized by progressive loss of muscle strength and motor function ranging from the extremely severe, the neonatal onset type 1, to the mild type 4 arising in the adult life. All the clinical variants share the same molecular defect, the difference being driven mainly by the copy number of SMN2 gene, a centromeric gene nearly identical to SMN1 with a unique C to T transition in Exon 7 that results in exclusion of Exon 7 during post-transcriptional processing. In all the types of SMA the clinical picture is characterized by hypotonia, weakness and areflexia. Clinical severity can vary a lot between the four main recognized types of SMA. As for the most of patients affected by different neuromuscular disorders, also in SMA fatigability is a major complaint as it is frequently reported in common daily activities and negatively impacts on the overall quality of life. The increasing awareness of fatigability as an important dimension of impairment in Neuromuscular Disorders and particularly in SMA, is making it both a relevant subject of study and identifies it as a fundamental therapeutic target. In this review, we aimed to overview the current literature articles concerning this problem, in order to highlight what is known and what deserves further research.

Keywords: SMA1; SMA2; SMA3; SMN1 gene; neuromuscular fatigue; skeletal muscle.

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Conflict of interest statement

The authors declare no conflict of interest.

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