What Is CMT-PSAT1?
CMT-PSAT1 is a type of CMT caused by autosomal dominant or autosomal recessive mutations in the PSAT1 gene. This gene provides instructions for making an enzyme in the pathway that produces the amino acid serine, which supports nerve cell function. Mutations in the PSAT1 gene disrupt this function, leading to impaired nerve signal transmission.
CMT-PSAT1 can be either autosomal dominant or autosomal recessive, meaning that sometimes it’s just one of the gene’s two copies with a CMT-causing mutation, and sometimes it’s both copies.
Clinical Features
The age of symptom onset in CMT-PSAT1 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-PSAT1 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-PSAT1 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.
