What Is dHMN-AARS1?
dHMN-AARS1 is a type of CMT caused by autosomal dominant mutations in the AARS1 gene. This gene provides instructions for making alanyl-tRNA synthetase, an enzyme that attaches the amino acid alanine to its transfer RNA during protein synthesis. Mutations in the AARS1 gene disrupt this function, leading to impaired nerve signal transmission.
dHMN-AARS1 is autosomal dominant, meaning that just one of the gene’s two copies needs a mutation to cause this subtype.
Clinical Features
The age of symptom onset in dHMN-AARS1 is variable, ranging from childhood to adulthood. As a motor neuropathy, dHMN-AARS1 primarily affects the most distal points, with weakness and atrophy of the feet and hands, and little to no involvement of the sensory nerves. Nerve conduction studies usually show somewhat slowed conduction velocities and reduced amplitudes, consistent with an axonal form of CMT.
dHMN-AARS1 symptoms may include:
- Weakness and atrophy in the feet and lower legs
- Foot drop
- Reduced or absent reflexes
- A steppage-style walking pattern
- Foot deformities, including high arches, and hammertoes (clawed toes)
- Progressive involvement of the hands
- Difficulty with fine motor skills and manual dexterity
- Additional symptoms not listed here
Disease Course
dHMN-AARS1 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.
