GNE Myopathy

Abstract

GNE myopathy is an adult onset disorder due to recessive mutations in the UDP N-acetylglucosamine 2- epimerase/N-acetylmannosamine kinase gene. It is a distal myopathy with relative sparing of the quadriceps manifesting usually in the third decade and slowly progressive to involve other limb muscles. Unusual features like proximal onset, neurogenic pattern and late respiratory involvement have been described. This is a worldwide disease with some high prevalence clusters due to founder mutations. Its typical muscle histology includes ‘rimmed’ vacuoles and cytoplasmic inclusions, thus it was called in the past hereditary inclusion body myopathy (HIBM) and distal myopathy with rimmed vacuoles (DMRV). Since GNE encodes a bi-functional enzyme, essential to sialic acid synthesis, sialylation defect is suspected as an important pathogenic factor, yet it does not fully explain the mechanism. Defects in this gene also account for macrothrombocytopenia and sialuria. Histopathology, imaging and other diagnostic features are reviewed. Potential therapeutic methods and future developments are discussed.