Skeletal muscle training for spinal muscular atrophy type 3 (Protocol).

Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease caused by a genetic mutation in the survival motor neuron 1 (SMN1) gene (5q11.2-q13.3) (Lefebvre 1995). With an incidence of one in 10,000 live births, it is the leading genetic cause of infant death (Lunn 2008; Mercuri 2012). SMA is characterized by degeneration of spinal cord α-motor neurons, which results in progressive proximal muscle weakness, fatigue, scoliosis, nutritional problems, respiratory complications, and severe functional limitations. SMA has a broad clinical spectrum but in general can be classified into four clinical types on the basis of age of onset and maximum motor function achieved (Mercuri 2012). SMA type 3 (Kugelberg-Welander disease) is the mildest subtype but shows large clinical heterogeneity, which can be further classified into type 3a (clinical symptoms before three years of age) and type 3b (clinical symptoms after three years of age) (Zerres 1997). Symptoms become evident after the age of 18 months. Children generally reach all major milestones, including independent walking, but their level of motor performance varies greatly. Some children are hardly able to stand up and take a few steps unaided, while others walk well, are able to climb stairs, and mainly experience problems in running and sports (Rudnik-Schöneborn 2001). Long-term follow-up studies (follow-up time of two to 20 years) in people with SMA type 2 and type 3 suggest a very slow deterioration of muscle strength and motor function that takes years to detect (Deymeer 2008; Kaufmann 2012; Werlauff 2012). Nevertheless, about 50% of people with SMA type 3 will lose independent ambulation during the second decade of life and only a small subgroup will remain ambulatory throughout life (Mercuri 2012; Russman 1996). In general people with SMA type 3b perform better on functional outcome measures, such as the six-minute walk test and the Hammersmith Functional Motor Scale Expanded, in comparison to people with SMA type 3a (Mazzone 2013; Montes 2010). There is no proven effective drug treatment for SMA type 3 (Wadman 2012), and current standards of care concentrate on SMA-associated complications, such as impaired mobility, scoliosis, fatigue, and respiratory infections. (aut. ref.