Peripheral neuropathy as initial sign of mitochondrial disorder

Charcot‐Marie‐Tooth disease constitutes a clinically and genetically heterogeneous group of hereditary motor and sensory peripheral neuropathies. On the basis of electrophysiologic properties and histopathology, CMT has been divided into demyelinating (type 1) and axonal (type 2) neuropathies. The form of Charcot‐Marie‐Tooth neuropathy that maps to Xq13 may present mild electrophysiological changes (NCV > 40 M/s), mixed neuropathy (NCV: Intermediate (30–40 M/s), or demyelinating neuropathy (NCV: Slow (<37 M/s). On molecular grounds, CMTX is caused by mutations in GJB1 gene, coding for Connexin 32 protein. A 42‐year‐old man, with no other affected family members, was clinically evaluated for CMT. Three years ago he noticed thumb abductor atrophy and then leg muscle atrophy. He presented with hand and leg muscle atrophy, bilateral pes cavus, areflexia, and apallesthesia. The median and ulnar motor NVC were 35–38 m/s, and the median sensory NVC was 35 m/s. Both motor and sensory nerve action potentials were markedly reduced. After exclusion of CMT1A and 1B, analysis for CMTX was performed. The mutation screening of GJB1 gene showed a 9bp insertion upstream the 194ATG codon (Met194) with preservation of the downstream sequence. The three new amino acids (Thr‐Val‐Phe) inserted are localized between the end of the second extracellular domain and the beginning of the fourth transmembrane domain. This is the first 9bp insertion found in GJB1 gene; a genotype‐phenotype correlation may be deduced.