β-enolase deficiency, a new metabolic myopathy of distal glycolysis

Authors

  • Giacomo P. Comi MD,

    Corresponding author
    1. Centro Dino Ferrari, Istituto di Clinica Neurologica, Università degli Studi di Milano, I.R.C.C.S. Ospedale Maggiore Policlinico, Milan, Italy
    • Istituto di Clinica Neurologica, Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milan, Italy
    Search for more papers by this author
  • Francesco Fortunato BS,

    1. Centro Dino Ferrari, Istituto di Clinica Neurologica, Università degli Studi di Milano, I.R.C.C.S. Ospedale Maggiore Policlinico, Milan, Italy
    Search for more papers by this author
  • Sabrina Lucchiari PhD,

    1. Centro Dino Ferrari, Istituto di Clinica Neurologica, Università degli Studi di Milano, I.R.C.C.S. Ospedale Maggiore Policlinico, Milan, Italy
    Search for more papers by this author
  • Andreina Bordoni BS,

    1. Centro Dino Ferrari, Istituto di Clinica Neurologica, Università degli Studi di Milano, I.R.C.C.S. Ospedale Maggiore Policlinico, Milan, Italy
    Search for more papers by this author
  • Alessandro Prelle MD,

    1. Centro Dino Ferrari, Istituto di Clinica Neurologica, Università degli Studi di Milano, I.R.C.C.S. Ospedale Maggiore Policlinico, Milan, Italy
    Search for more papers by this author
  • Stefano Jann MD,

    1. Division of Neurology, Ospedale Niguarda Cà Granda, Milan, Italy
    Search for more papers by this author
  • Angélica Keller PhD,

    1. Laboratoire CRRET-UPRESA CNRS 7053, Université Paris 12, Créteil, France
    Search for more papers by this author
  • Patrizia Ciscato BS,

    1. Centro Dino Ferrari, Istituto di Clinica Neurologica, Università degli Studi di Milano, I.R.C.C.S. Ospedale Maggiore Policlinico, Milan, Italy
    Search for more papers by this author
  • Sara Galbiati MD,

    1. Centro Dino Ferrari, Istituto di Clinica Neurologica, Università degli Studi di Milano, I.R.C.C.S. Ospedale Maggiore Policlinico, Milan, Italy
    Search for more papers by this author
  • Luca Chiveri MD,

    1. Centro Dino Ferrari, Istituto di Clinica Neurologica, Università degli Studi di Milano, I.R.C.C.S. Ospedale Maggiore Policlinico, Milan, Italy
    Search for more papers by this author
  • Yvan Torrente MD,

    1. Centro Dino Ferrari, Istituto di Clinica Neurologica, Università degli Studi di Milano, I.R.C.C.S. Ospedale Maggiore Policlinico, Milan, Italy
    Search for more papers by this author
  • Guglielmo Scarlato MD,

    1. Centro Dino Ferrari, Istituto di Clinica Neurologica, Università degli Studi di Milano, I.R.C.C.S. Ospedale Maggiore Policlinico, Milan, Italy
    Search for more papers by this author
  • Nereo Bresolin MD

    1. Centro Dino Ferrari, Istituto di Clinica Neurologica, Università degli Studi di Milano, I.R.C.C.S. Ospedale Maggiore Policlinico, Milan, Italy
    2. IRCCS E. Medea, Associazione La Nostra Famiglia, Bosisio Parini, Italy
    Search for more papers by this author

Abstract

A severe muscle enolase deficiency, with 5% of residual activity, was detected in a 47-year-old man affected with exercise intolerance and myalgias. No rise of serum lactate was observed with the ischemic forearm exercise. Ultrastructural analysis showed focal sarcoplasmic accumulation of glycogen β particles. The enzyme enolase catalyzes the interconversion of 2-phosphoglycerate and phosphoenolpyruvate. In adult human muscle, over 90% of enolase activity is accounted for by the β-enolase subunit, the protein product of the ENO3 gene. The β-enolase protein was dramatically reduced in the muscle of our patient, by both immunohistochemistry and immunoblotting, while α-enolase was normally represented. The ENO3 gene of our patient carries two heterozygous missense mutations affecting highly conserved amino acid residues: a G467A transition changing a glycine residue at position 156 to aspartate, in close proximity to the catalytic site, and a G1121A transition changing a glycine to glutamate at position 374. These mutations were probably inherited as autosomal recessive traits since the mother was heterozygous for the G467A and a sister was heterozygous for the G1121A transition. Our data suggest that ENO3 mutations result in decreased stability of mutant β-enolase. Muscle β-enolase deficiency should be considered in the differential diagnosis of metabolic myopathies due to inherited defects of distal glycolysis.

Ancillary