Motor axonal neuropathy associated with GNE mutations

Background: Mutations in the GNE gene have been so far described as predominantly associated with distal lower-limb myopathies. Recent reports describe mutations in this gene in patients with peripheral neuropathy and motor neuron disease. Methods: We describe three patients displaying motor neuropathy in association with GNE mutations. Clinical, electrophysiological, imaging, pathological, and genetic data are presented in a retrospective manner. Results: The three patients had different phenotypes, ranging from mildly progressive lower limb weakness to a rapidly progressive 4-limb weakness. Genetic testing revealed GNE gene mutations in all patients; of those mutations, p.(His186Arg) has not been previously reported. All patients showed evidence of axonal motor nerve involvement on electrodiagnostic examination and/or muscle biopsy. Conclusions: Nerve involvement associated with GNE gene mutations may be an underdiagnosed pathology and may influence clinical presentation and disease progression.