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

A severe muscle enolase deficiency, with 5% of residual activity, was detec ted in a 47-year-old man affected with exercise intolerance and myalgias. N o rise of serum lactate was observed with the ischemic forearm exercise. Ul trastructural analysis shows focal sarcoplasmic accumulation of glycogen be ta particles. The enzyme enolase catalyzes the interconversion of 2-phospho glycerate and phosphoenolpyruvate. In adult human muscle, over 90% of enola se activity is accounted for by the beta -enolase subunit, the protein prod uct of the ENO3 gene. The beta -enolase protein was dramatically reduced in the muscle of oar patient, by both immunohistochemistry and immunoblotting , while alpha -enolase was normally represented. The ENO3 gene of our patie nt carries two heterozygous missense mutations affecting highly conserved a mino acid residues: a G467A transition changing a glycine residue at positi on 156 to aspartate, in close proximity to the catalytic site, and a G1121A transition changing a glycine to glutamate at position 374. These mutation s were probably inherited as autosomal recessive traits since the mother wa s heterozygous for the G467A and a sister was heterozygous for the G1121A t ransition. Our data suggest that EN03 mutations result in decreased stabili ty of mutant beta -enolase. Muscle beta -enolase deficiency should be consi dered in the differential diagnosis of metabolic myopathies due to inherite d defects of distal glycolysis.