What Is dHMN-5A?
dHMN-5A is a type of CMT caused by autosomal dominant mutations in the GARS1 gene. This gene provides instructions for making glycyl-tRNA synthetase, an enzyme that attaches the amino acid glycine to its transfer RNA during protein synthesis. Mutations in the GARS1 gene disrupt this function, leading to impaired nerve signal transmission.
dHMN-5A 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-5A is variable, ranging from childhood to early adulthood. Unlike many forms of CMT, dHMN-5A predominantly affects the upper limbs, with weakness and atrophy of the hand muscles often appearing early. The lower limbs typically become involved as the disease progresses. As a distal hereditary motor neuropathy, dHMN-5A predominantly affects the motor nerves, with sensation typically preserved. Nerve conduction studies usually show somewhat slowed conduction velocities and reduced amplitudes, consistent with an axonal form of CMT.
dHMN-5A symptoms may include:
- Weakness in the hands, often as an early feature
- Muscle atrophy, particularly of the hand muscles
- Weakness in the feet and lower legs
- Difficulty with fine motor skills and manual dexterity
- Brisk reflexes
- Foot deformities, including high arches
- Foot drop
- Additional symptoms not listed here
Disease Course
dHMN-5A 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.
