Autosomal recessive intermediate Charcot-Marie-Tooth disease type A

Autosomal recessive intermediate Charcot-Marie-Tooth disease type A (RI-CMTA), also known as CMTRIA, is a rare inherited peripheral neuropathy caused by mutations in the GDAP1 gene (ganglioside-induced differentiation-associated protein 1). It belongs to the intermediate forms of Charcot-Marie-Tooth disease, meaning that nerve conduction velocities fall between the ranges typically seen in the demyelinating (CMT1) and axonal (CMT2) subtypes, generally between 25 and 45 m/s in motor nerves. The disease primarily affects the peripheral nervous system, leading to progressive weakness and wasting of the distal muscles of the legs and arms, sensory loss, foot deformities (such as pes cavus and hammertoes), and difficulty walking. Onset typically occurs in childhood or adolescence, and the severity can vary considerably even within the same family. The condition affects both motor and sensory nerves, and nerve biopsy or electrophysiological studies may show features of both axonal degeneration and demyelination. Patients often develop steppage gait due to foot drop, reduced or absent deep tendon reflexes, and may experience hand weakness that impairs fine motor skills as the disease progresses. Some patients may eventually require mobility aids such as ankle-foot orthoses or wheelchairs. Scoliosis and vocal cord paresis have been reported in some cases. There is currently no cure or disease-modifying therapy for RI-CMTA. Management is supportive and multidisciplinary, including physical therapy to maintain muscle strength and flexibility, occupational therapy for hand function, orthopedic interventions for foot deformities, and pain management when needed. Genetic counseling is recommended for affected families. Research into potential therapies, including gene-based approaches, is ongoing but remains in early stages.

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