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Neurotherapeutics

, Volume 15, Issue 4, pp 900–914 | Cite as

GNE Myopathy: Etiology, Diagnosis, and Therapeutic Challenges

  • Nuria Carrillo
  • May C. Malicdan
  • Marjan Huizing
Review

Abstract

GNE myopathy, previously known as hereditary inclusion body myopathy (HIBM), or Nonaka myopathy, is a rare autosomal recessive muscle disease characterized by progressive skeletal muscle atrophy. It has an estimated prevalence of 1 to 9:1,000,000. GNE myopathy is caused by mutations in the GNE gene which encodes the rate-limiting enzyme of sialic acid biosynthesis. The pathophysiology of the disease is not entirely understood, but hyposialylation of muscle glycans is thought to play an essential role. The typical presentation is bilateral foot drop caused by weakness of the anterior tibialis muscles with onset in early adulthood. The disease slowly progresses over the next decades to involve skeletal muscles throughout the body, with relative sparing of the quadriceps until late stages of the disease. The diagnosis of GNE myopathy should be considered in young adults presenting with bilateral foot drop. Histopathologic findings on muscle biopsies include fiber size variation, atrophic fibers, lack of inflammation, and the characteristic “rimmed” vacuoles on modified Gomori trichome staining. The diagnosis is confirmed by the presence of pathogenic (mostly missense) mutations in both alleles of the GNE gene. Although there is no approved therapy for this disease, preclinical and clinical studies of several potential therapies are underway, including substrate replacement and gene therapy-based strategies. However, developing therapies for GNE myopathy is complicated by several factors, including the rare incidence of disease, limited preclinical models, lack of reliable biomarkers, and slow disease progression.

Key Words

GNE myopathy genetics rare diseases gene therapy ManNAc sialic acid. 

Notes

Acknowledgments

This research was supported by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health.

Required Author Forms

Disclosure forms provided by the authors are available with the online version of this article.

Supplementary material

13311_2018_671_MOESM1_ESM.pdf (499 kb)
ESM 1 (PDF 498 kb)

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Copyright information

© This is a U.S. government work and its text is not subject to copyright protection in the United States; however, its text may be subject to foreign copyright protection 2018

Authors and Affiliations

  1. 1.Medical Genetics Branch, National Human Genome Research Institute (NHGRI)National Institutes of HealthBethesdaUSA

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