Charcot–Marie–Tooth+Disease

Charcot–Marie–Tooth disease

__Root Cause__: This disease is caused by hereditary genetic mutations which cause demyelination of the myelin sheath which covers the axon of nerve cells. Additionally, as a result of the improper maintenance of the myelin sheath, the axon can become damaged (Young & Suter, 2001). These cause thickening of nerves, often in the feet and lead to deformities, severe pain, muscle atrophy and weakness.



__Affected cell types__: This disease mainly affects nerve cells and seems to most commonly effect muscle and nerve cells in the extremities.

__Historical Background__: The disease was described independently by the three physicians Jean-Martin Charcot, Pierre Marie France and Howard Henry Tooth (Berciano et al., 2011). The disease is mostly prevalent in Spain.

__Common Symptoms__: The first symptoms are leg weakness and muscle atrophy. Sometimes pain can be associated with the disease, most likely due to damaged nerves, as a result of the cause of the disease. The disease causes slower neural cell firing leading to spasmodic muscle contractions. Additionally, foot deformities may occur such as foot drop, hammertoes and high arches in later stages.

__Standard Treatments__: Because the disease is a hereditary genetic disorder, there is no cure. Most treatments involve physical therapy to maintain muscle strength. Surgery or braces are sometimes used to correct malformation of the feet.

__Current Research__: In 2013, a study found that the same genetic mutation which causes CMT disease, also affects mitochondria and endoplasmic reticulum contact and changes calcium ion flow in the ER (Pla-Martín et al., 2013).

In 2012, a study showed that the genes which cause CMT disease are also highly linked to proteins which are involved in intercellular transport and regulation of intercellular traffic (Bucci, Bakke, & Progida, 2012).

Another recent study from 2013, showed that the expression of MAG and Nec14, adhesion proteins in the axon surface were changed in patients with CMT as compared to those who do not have the genetic disorder. MAG, which is vital to sustaining proper axon-gila contact, is increased in expression in those with CMT, perhaps due to the increased need to counteract the derogatory effects of the disease (Kinter et al., 2013).

__References__: Berciano, J., Gallardo, E., García, A., Pelayo-Negro, A. L., Infante, J., & Combarros, O. (2011). Charcot-Marie-Tooth disease: a review with emphasis on the pathophysiology of pes cavus. //Revista Española de Cirugía Ortopédica y Traumatología (English Edition)//, //55//(2), 140–150. doi:http://dx.doi.org/10.1016/S1988-8856(11)70296-6 Bucci, C., Bakke, O., & Progida, C. (2012). Charcot–Marie–Tooth disease and intracellular traffic. //Progress in Neurobiology//, //99//(3), 191–225. doi:10.1016/j.pneurobio.2012.03.003 Kinter, J., Lazzati, T., Schmid, D., Zeis, T., Erne, B., Lützelschwab, R., … Schaeren-Wiemers, N. (2013). An essential role of MAG in mediating axon–myelin attachment in Charcot–Marie–Tooth 1A disease. //Neurobiology of Disease//, //49//, 221–231. doi:10.1016/j.nbd.2012.08.009 Pla-Martín, D., Rueda, C. B., Estela, A., Sánchez-Piris, M., González-Sánchez, P., Traba, J., … Palau, F. (2013). Silencing of the Charcot–Marie–Tooth disease-associated gene GDAP1 induces abnormal mitochondrial distribution and affects Ca2 + homeostasis by reducing store-operated Ca2 + entry. //Neurobiology of Disease//, //55//, 140–151. doi:10.1016/j.nbd.2013.03.010