Muscular atrophy

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. 

Trinucleotide sequences that increase in number (microsateUite instability) can cause disease. The unstable p(CGG) repeat sequence is associated with the fragile X syndrome. Other trinucleotide repeats that undergo dynamic mutation (usually an increase) are associated with Huntington s chorea (CAG), myotonic dystrophy (CTG), spinobulbar muscular atrophy (CAG), and Kennedy s disease (CAG). 

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. 

La Spada, A. R., Roling, D. B., Harding, A. E. et al. Meiotic stability and genotype-phenotype correlation of the trinucleotide repeat in X-linked spinal and bulbar muscular atrophy. Nat. Genet. 2 301-304,1992. 

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. 

Kennedy s disease/ spinobulbar muscular atrophy [6,7] AR Xql3-21 not determined 9-36... 

Arbizu, T., Santamaria, J., Gomez, J. M. et al. A family with adult spinal and bulbar muscular atrophy, X-linked inheritance and associated testicular failure./. Neurol. Sci. 59 371-382,1983. 

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

Huntington disease (HD) is the prototypic disease caused by expansion of unstable GAG repeat. It primarily affects striatal neurons. It is a mid-life onset disorder characterized by unvoluntary movements (chorea), personality changes and dementia that progress to death within 10-20 years of onset. There are currently no treatment to delay or prevent appearance of the symptoms in the patients. Other diseases in this class include spinocerebellar ataxias (SCA) 1, 2, 3 (also known as Machado-Joseph disease, MJD), 6, and 7, DRPLA, and spinobulbar muscular atrophy (SMA, also known as Kennedy s disease) (Zoghbi and Orr 2000). 

SBMA In addition to HD, NaBu has also been reported to be effective in treating spinal and bulbar muscular atrophy (SBMA) (Minamiyama et al, 2004), an inheritable motorneuron disease caused by an expanded polyglutamine-repeat within the androgen receptor. SBMA is associated with motorneuron loss in the spinal cord and brain stem as well as a sub-clinical loss of sensory neurons in the dorsal root ganglia resulting in skeletal muscle atrophy and weakness (Sobue et al, 1989 ... 

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