Respiratory dysfunction in patients severely affected by GNE myopathy (distal myopathy with rimmed vacuoles)

Neuromuscul Disord. 2013 Jan;23(1):84-8. doi: 10.1016/j.nmd.2012.09.007. Epub 2012 Nov 2.


GNE myopathy is a rare and mildly progressive autosomal recessive myopathy caused by GNE mutations. Respiratory dysfunction has not been reported in GNE myopathy patients. In this study, we retrospectively reviewed the respiratory function of 39 severely affected GNE myopathy patients (13 men, 26 women) from medical records, and compared these parameters with various other patient characteristics (e.g., GNE mutations, age at onset, creatine kinase levels, and being wheelchair-bound) for correlations. The mean % forced vital capacity [FVC] was 92 (26) (range, 16-128). In 12/39 (31%) patients, %FVC was <80%. Of these 12 patients, 11 (92%) were entirely wheelchair-dependent. These patients exhibited significantly earlier onset (20 [4] vs. 30 [8] years, p<0.001) and lower creatine kinase levels (56 [71] vs. 279 [185] IU/L) than patients with normal respiratory function. Two patients exhibited severe respiratory failure and required non-invasive positive pressure ventilation. Patients with a homozygous mutation in the N-acetylmannosamine kinase domain exhibited lower %FVC, while only one compound heterozygous patient with separate mutations in the uridinediphosphate-N-acetylglucosamine 2-epimerase and the N-acetylmannosamine kinase domains had respiratory dysfunction. Our results collectively suggest that GNE myopathy can cause severe respiratory failure. Respiratory dysfunction should be carefully monitored in patients with advanced GNE myopathy characterized by early onset and homozygous homozygous mutations in the N-acetylmannosamine kinase domain.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Creatine Kinase / metabolism
  • Distal Myopathies / epidemiology
  • Distal Myopathies / genetics*
  • Distal Myopathies / physiopathology*
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Mobility Limitation
  • Mutation / genetics*
  • Phosphotransferases (Alcohol Group Acceptor) / genetics*
  • Respiratory System / physiopathology*
  • Retrospective Studies
  • Vital Capacity / physiology


  • Phosphotransferases (Alcohol Group Acceptor)
  • N-acylmannosamine kinase
  • Creatine Kinase

Supplementary concepts

  • Distal myopathy, Nonaka type