To describe atypical myopathological findings in 2 patients with GNE myopathy.

GNE myopathy is a distal myopathy due to recessive mutations in GNE, which encodes a bifunctional enzyme critical for sialic acid biosynthesis. Rimmed vacuoles, although nonspecific, are the pathological hallmark of GNE myopathy. On the other hand, glycogen accumulation in muscle fibers is the canonical finding of glycogen storage diseases and is not known to occur in GNE myopathy.

Retrospective review of two patients. 

Patient 1 was a 28-year-old female who presented with an 8-year history of recurrent falls as a result of bilateral foot drop, and later developed bilateral hand weakness. Her older brother had similar symptoms. Patient 2 was a 23-year-old male with a history of bilateral foot drop since age 18. His weakness later progressed to involve his hands.  On exam, both patients had generalized weakness, most severely affecting the anterior compartment of the legs. Their muscle biopsies showed several fibers harboring rimmed vacuoles, some of which contained PAS-positive, diastase labile material. Next generation sequencing of myopathy-related genes identified pathogenic variants in GNE in both patients (patients 1: homozygous p. Met743Thr; patient 2: compound heterozygous p.Val727Met and  p.Arg160Gln). No mutations or variants of unknown significance in glycogen storage myopathy genes were detected.

We describe glycogen accumulation in muscle fibers of patients with GNE myopathy. The presence of PAS-positive vacuoles should not exclude a diagnosis of GNE myopathy, especially in patients with early onset distal myopathy.