What Is CMT-SORD?
CMT-SORD is a type of CMT caused by autosomal recessive mutations in the SORD gene. This gene provides instructions for making sorbitol dehydrogenase, an enzyme that breaks down the sugar alcohol sorbitol as part of normal glucose metabolism. Mutations in the SORD gene disrupt this function, leading to impaired nerve signal transmission.
CMT-SORD is autosomal recessive, meaning that both copies of the gene must have a mutation to cause this subtype.
Clinical Features
The age of symptom onset in CMT-SORD is variable, typically beginning in childhood or adolescence. The disease results from a buildup of sorbitol, a sugar alcohol that the sorbitol dehydrogenase enzyme normally breaks down. It is motor-predominant, with weakness and atrophy that begin in the lower limbs. Nerve conduction studies usually show somewhat slowed conduction velocities and reduced amplitudes, consistent with an axonal form of CMT.
CMT-SORD symptoms may include:
- Weakness in the feet and lower legs
- Muscle atrophy
- Reduced or absent reflexes
- Reduced sensation
- A steppage-style walking pattern
- Foot deformities, including high arches, and hammertoes (clawed toes)
- Progressive involvement of the hands and forearms
- Difficulty with fine motor skills and manual dexterity
- Additional symptoms not listed here
Disease Course
CMT-SORD shows wide variability in severity and progression. Some individuals are mildly affected, while others develop a more severe disease. Disease progression is generally slow, and life expectancy is not reduced.
