What Is CMT2EE?
CMT2EE is a type of CMT caused by mutations in the MPV17 gene. This gene provides instructions for producing a protein involved in maintaining mitochondrial DNA stability and normal mitochondrial function. Mutations in the MPV17 gene disrupt mitochondrial maintenance in peripheral nerve cells, leading to impaired nerve signal transmission.
CMT2EE is autosomal recessive, meaning that both of the gene’s two copies must have a CMT-causing mutation to cause this subtype.
Clinical Features
The age of symptom onset in CMT2EE is usually in the teens. Symptoms typically begin in the lower extremities and progress over time to involve the upper limbs. Nerve conduction studies usually show somewhat slowed conduction velocities and reduced amplitudes, consistent with an axonal form of CMT.
CMT2EE symptoms may include:
- Weakness in the feet and lower legs
- Muscle atrophy
- Foot drop
- A steppage-style walking pattern
- Reduced sensation
- Reduced or absent reflexes
- Muscle biopsy shows:
- Mitochondrial respiratory chain deficiency
- Ragged red fibers
- Subsarcolemmal accumulation of abnormal mitochondria
- Mitochondrial DNA deletions (in some patients)
- Foot deformities, including high arches and hammertoes (clawed toes)
- Progressive involvement of the hands and forearms
- Difficulty with fine motor skills and manual dexterity
- Balance difficulties
- Additional symptoms not listed here
Disease Course
CMT2EE 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.
