Background: Charcot-Marie-Tooth 2A (CMT2A) is caused by mutations in mitochondrial fusion protein mitofusin 2 (MFN2). CMT2A had a large variety of clinical symptoms and several cohort studies were published recently. This study is to summarized the clinical, electrophysiological, pathological and genetic features in Han Chinese CMT2A.
Methods: 20 patients from 12 unrelated Chinese families with MFN2 related CMT2A were collected. Clinical symptom, nerve conduction velocity study, sural nerve pathology and MFN2 gene mutation were retrospectively analyzed.
Results: We confirmed MFN2 gene mutation in 12 indexes. Nineteen of 20 (95%) patients were classified as early onset phenotypes of CMT2A, including four cases (20%) with infantile onset. Motor nerve conduction velocity (MNCV) of median nerve was above 38m/s in 50% of patients and not recordable in remaining patients. MNCV was not affected by onset age, disease course and mutation site in different patients and MNCV had no correlation with severity of symptoms. Sural nerve biopsy revealed mixed axonal and demyelination change. Loss of myelinated fibers and atypical onions was found in all cases. Electron microscopic (EM) examination of sural nerve confirmed mitochondrial vacuation and aggregation both in myelinated and unmyelinated axons. Eight mutations were detected in 12 indexes, including two novel mutations. The amino acid residue at position 94 of MFN2 protein was a hot spot in Han Chinese patients, followed by R104W.
Conclusions: Eraly onset, even infantile onset was more common in our Chinese population. MNCV of median nerve could be either above 38m/s or unrecordable in CMT2A. Pathologically, mixed axon and myelin change should be considered since onion change was frequently observed in most CMT2A.
Keywords: Axonal neuropathy; Charcot–Maria–Tooth; Early onset; Hereditary neuropathy; Mitofusin 2; Pathology.
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