What Is CMT-HADHB?
CMT-HADHB is a type of CMT caused by autosomal recessive mutations in the HADHB gene. This gene provides instructions for making one part of the mitochondrial trifunctional protein, an enzyme complex responsible for breaking down long-chain fatty acids for energy inside mitochondria. Mutations in the HADHB gene disrupt this energy-producing process in peripheral nerve cells, leading to impaired nerve signal transmission.
CMT-HADHB 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-HADHB is variable, ranging from childhood to adulthood. 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.
CMT-HADHB symptoms may include:
- Weakness in the feet and lower legs
- Muscle atrophy
- Foot drop
- 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-HADHB 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.
