Case ReviewGNE Myopathy as a Myofibrillar Myopathy: Potential Important Disease Mechanism Implied by Muscle BiopsyChrisman, Christina MD*,†; McKeever, Paul E. MD, PhD‡Author Information *Department of Neurology, Neuromuscular Medicine, Banner University Medical Center-Phoenix, Phoenix, AZ; †Neurology, University of Arizona College of Medicine-Phoenix, Phoenix, AZ; and ‡Neuropathology, Department of Pathology, Michigan Medicine, University of Michigan, Ann Arbor, MI. Reprints: Christina Chrisman, MD, Banner University Medical Center, Neuroscience Institute, 755 E McDowell Rd, 3rd Floor, Phoenix, AZ 85006 (e-mail: [email protected]). C. Chrisman speaker for Alexion on Soliris (eculizumab) 2019–2020, served on advisory board for Biogen on Spinraza (nusinersen) 2018. The remaining author reports no conflicts of interest. Journal of Clinical Neuromuscular Disease: December 2020 - Volume 22 - Issue 2 - p 90-96 doi: 10.1097/CND.0000000000000317 Buy Metrics Abstract We report a case of 2 sisters in their 20s with genetically confirmed UDP-N-acetylglucoasmine 2-epimerase/N-acetylmannosamine kinase myopathy along with muscle biopsy findings. Both patients described slowly progressive signs of distal-predominant weakness since adolescence that had been dismissed as “clumsiness.” Exam and electrodiagnostic testing suggested a predominately distal myopathy. Muscle biopsy of the left tibialis anterior revealed rimmed vacuoles and, interestingly, also had characteristic features of a myofibrillar myopathy. Genetic testing confirmed a diagnosis of autosomal recessive GNE myopathy in both patients. GNE myopathy has not typically been considered a myofibrillar myopathy, but this case raises possibilities worthy of further exploration. It is possible that the unique combination of pathogenic alleles in GNE reported here has led to a novel form of GNE myopathy with muscle biopsy showing characteristic features of GNE myopathy and myofibrillar myopathy. The other possibility is that myofibrillar myopathy may be a more common feature of GNE myopathies than classically described. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.