Atrophy spinal muscular

From the practical viewpoint it is important to be able to distinguish infants and children with this condition from less benign disorders such as the spinal muscular atrophies. Careful histochemical assessment of muscle biopsies with histographic analysis is recommended. Most biopsies from CFTD patients show type 1 fibers which are small in relation to type 2 fibers. A revised definition of CFTD states that... 

All three forms of spinal muscular atrophy are inherited as autosomal recessive disorders, linked to chromosome 5q. Prenatal diagnosis using closely linked markers is now available. A rare, autosomal dominant form of juvenile SMA is similar in expression to the recessive forms, but 5q is not involved. 

Diseases selectively targeting spinal cord and brainstem motor neurons (e.g. amyotrophic lateral sclerosis and the familial spinal muscular atrophies) or the presynaptic component of neuromuscular junctions (e.g. Lambert-Eaton syndrome, botulism and Ixodes tick paralysis) cause weakness without sensory impairment. Disorders involving the enteric nervous system (e.g. Chagas disease and Hirschsprung s disease) impair bowel motility. 

Pellizzoni, L., Kataoka, N., Charroux, B. and Dreyfuss, G. A novel function for SMN, the spinal muscular atrophy disease gene product, in pre-mRNA splicing. Cell 95 615-624, 1998. 

Anderson, K. and Talbot, K. Spinal muscular atrophies reveal motor neuron vulnerability to defects in ribonucleo-protein handling. Curr. Opin. Neurol. 16 595-599,2003. 

Le, T. T., Pham, L. T., Butchbach, M. E. et al. SMNA7, the major product of the centromeric survival motor neuron (SMN2) gene, extends survival in mice with spinal muscular atrophy and associates with full-length SMN. Hum. Mol. Genet. 14 845-857, 2005. 

Cork, L. C., Griffin, I. W., Adams, R. J. and Price, D. L. Motor neuron disease spinal muscular atrophy and amyotrophic lateral sclerosis. Animal model hereditary canine spinal muscular atrophy. Am. J. Pathol. 100 599-602,1980. 

Grohmann, K., Varon, R., Stolz, P. et al. Infantile spinal muscular atrophy with respiratory distress type 1 (SMARD1). Ann. Neurol. 54 719-724, 2003. 

EM electron microscopy HCSMA hereditary canine spinal muscular atrophy... 

There are many other neurodegenerative diseases, some with a high incidence, and others rare. They include Parkinson disease (p. 1790), Huntington disease (Table 26-4), spinal muscular atrophy (SMA a leading hereditary cause of infant mortality),1162a b amyotrophic lateral sclerosis (ALS), prion diseases (Box 29-E), ataxias, and other diseases caused by triple-repeat DNA sequences (Table 26-4) and X-linked adrenoleukodystrophy (ALD p. 945).1163 In the last, membrane function is disrupted. Although these diseases arise from a variety of causes many of them have in common amyloidosis, the deposition of insoluble proteins in or around neurons.11633... 

Key words Motor neuron diseases, amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), peripheral neuropathies, Charcot-Marie-Tooth diseases, hereditary motor and/or sensory neuropathies (HSMNs), congenital myasthenic syndromes, neuromuscular junction, muscular dystrophies, Duchenne s disease. 

The disease models can be grouped into four primary categories (Fig. 20.1). (1) Motor neuron diseases, in which the death of motor neuron somata in the spinal cord results in denervation of the muscles, progressive flaccid paralysis, and usually premature death. In humans, examples of such diseases would include amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). (2) Peripheral neuropathies, in which axonal integrity or conduction is not maintained, resulting in axon degeneration and impaired connectivity of the nervous system and the musculature. 

O., Jablonka, S., Le, T. T., Andreassi, C., et al. (2003) A transgene carrying an A2G missense mutation in the SMN gene modulates phenotypic severity in mice with severe (type I) spinal muscular atrophy. J Cell Biol 160,41-52. 

Schrank, B., Gotz, R, Gunnersen, J. M., Ure, J. M., Toyka, K. V., Smith, A. G., et al. (1997) Inactivation of the survival motor neuron gene, a candidate gene for human spinal muscular atrophy, leads to massive cell death in early mouse embryos. Proc Natl Acad Sci USA 94,9920-9925. 

Lefebvre S, Burglen L, Reboullet S, Clermont O, Burlet P, Viollet L, Benichou B, Cruaud C, Millasseau P, Zeviani M, et al. Identification and characterization of a spinal muscular atrophy-determining gene. Cell 1995 80(1) 155—165. 

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