Spinal muscular atrophy, progressive

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. 

Another motor neuron disease, which is rare and x-linked inheritance, shows certain similarities with ALS but has a much more benign course. It is so-called Kennedy s disease or x-linked spino-bulbar muscular atrophy (X-SBMA). It is caused by a mutation of the androgen receptor gene. A progressive spinal. 

Mutations in the AR cause resistance to the actions of testosterone and dihydrotestosterone. Male sexual differentiation and pubertal development therefore are incomplete. Other AR mutations occur in patients who have spinal and bulbar muscular atrophy, known as Kennedy s disease. These patients have an expansion of the CAG repeat, which codes for glutamine, at the amino terminus of the AR they exhibit very mild androgen resistance—manifest principally by gynecomastia—but progressively severe motor neuron atrophy, the basis of which is poorly understood. 

Motor neuron disease is also known as amyotrophic lateral sclerosis. It is a condition in which there is loss of spinal motor neurons and neurons of descending motor pathways from pyramidal cells of the cerebral cortex. The disease results in rapidly progressing muscular weakness, muscle atrophy, fasciculations, spasticity, difficulty speaking. 

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