Long term clinical follow-up and natural history in a cohort of Italian patients with GNE myopathy: the experience of a single centre

Background: GNE myopathy is a muscle disease due to mutations in the GNE gene, encoding for the key enzyme of sialic acid biosynthesis. This disorder firstly involves distal lower limb muscles and slowly progresses to scapular girdle and distal upper limb muscles. Patients/Methods: We describe a cohort of 13 patients (9/13 women and 4/13 men) affected by GNE myopathy, followed on average for 15 years. The diagnoses were based on clinical evaluation, EMG, muscle MRI/CT, muscle biopsy and genetic analysis. Results: Our patients have a mean age of 44 years old. The onset of symptoms was between the second and third decade of life. In the early stage, every patient complained difficulty in walking caused by foot drop. Ten patients are now wheelchair-bound, and quadriceps is typically spared in each patient, as commonly described for GNE myopathy. Only one patient developed respiratory failure requiring non-invasive ventilation. EMG study revealed a myopathic pattern in quite all patients and muscle biopsy showed atrophic fibres with “rimmed” vacuoles. Finally, all our patients are genetically characterized: 4/13 present a homozygous mutation in GNE gene, 9/13 a compound heterozygous one. Conclusions: GNE myopathy is a very rare muscle disorder, probably under-diagnosed because of the large group of diseases manifesting with foot drop. Although that, it’s necessary to suspect it in case of distal and bilateral lower limb muscles weakness with quadriceps sparing. Several aspects of this myopathy are still unclear and there is no approved therapy for, but novel therapeutic strategies continue to be explored.