What Is dSMAX-3?
dSMAX-3 is a type of CMT caused by X-linked recessive mutations in the ATP7A gene. This gene provides instructions for making a copper-transporting protein essential to the normal function of motor nerve cells. Mutations in the ATP7A gene disrupt this function, leading to impaired nerve signal transmission.
dSMAX-3 is X-linked recessive. This means the gene lives on the X chromosome, and in people with two X chromosomes (chromosomal females), a mutation in both copies of the gene is needed to cause dSMAX-3. For individuals with one X and one Y chromosome (chromosomal males), a mutation in their single copy of the gene is sufficient to cause dSMAX-3.
Clinical Features
The age of symptom onset in dSMAX-3 is variable, ranging from childhood to adulthood. As a motor neuropathy, dSMAX-3 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.
dSMAX-3 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
dSMAX-3 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.
