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

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 beta 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 beta-enolase subunit, the protein product of the ENO3 gene. The beta-enolase protein was dramatically reduced in the muscle of our patient, by both immunohistochemistry and immunoblotting, while alpha-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 beta-enolase. Muscle beta-enolase deficiency should be considered in the differential diagnosis of metabolic myopathies due to inherited defects of distal glycolysis.

Characterization of porcine ENO3: genomic and cDNA structure, polymorphism and expression

“…As an early marker of human myogenesis [6], ENO3 is responsible for over 90% of the enolase activity in adult human muscle and plays an important role in muscle diseases [4]. In our study, we used the real-time PCR technique to examine the tissue expression of both ENO3 transcripts and expression changes of these mRNAs during three important stages of skeletal muscle development in different pig breeds.…”

“…In adult human muscle, over 90% of the enolase activity is accounted for by the beta-enolase subunit encoded by the ENO3 gene. Mutations in this gene can be associated with metabolic myopathies that may result from a decreased stability of the enzyme [4].…”

Transcriptome of the subcutaneous adipose tissue in response to oral supplementation of type 2 Leprdb obese diabetic mice with niacin-bound chromium

“…The enzyme catalyzes the interconversion of 2-phosphoglycerate and phosphoenolpyruvate. In adult human muscle, Ͼ90% of enolase activity is accounted for by the ␤-enolase subunit, the protein product of the ENO3 gene (17). The transcription of ENO3 is regulated by an intronic musclespecific enhancer that binds myocyte-specific enhancer factor-2 proteins and ubiquitous G-rich box-binding factors (21).…”

“…The transcription of ENO3 is regulated by an intronic musclespecific enhancer that binds myocyte-specific enhancer factor-2 proteins and ubiquitous G-rich box-binding factors (21). Deficiency in ␤-enolase leads to myopathy (17). In the order of the magnitude of change, the next NBC-sensitive gene in the fat tissue was calsequestrin.…”

Neuromuscular, cognitive and metabolic implications of McArdle Syndrome: a global overview

“…On these grounds, 14 distinct diseases have currently been identified:  Type I, or Von Gierke's disease, which develops due to glucose-6-phosphatase deficiency [5];  Type II, or Pompe's disease, which develops due to acid alpha glucosidase deficiency; it exhibits two different forms: early-onset (or the infantile form) and late-onset (or the juvenile/adult form) [6];  Type III, or Cori's disease, which develops due to alteration of a glycogen debranching enzyme (4-alpha glucanotransferase); it is subdivided into subtypes IIIa, IIIb, IIIc and IIId as a function of the degree of enzyme deficiency [7];  Type IV, or Andersen disease, which develops due to alteration of the glycogen branching enzyme [8];  Type V, or McArdle Syndrome (MS), which develops due to myophosphorylase deficiency [9];  Type VI, or Hers' disease, which develops due to liver phosphorylase deficiency [10]. Type VII results from phosphofructokinase deficiency [11], and types VIII and X were included in the latter category;  Type IX, which develops due to deficiency of the liver phosphorylase kinase isoform PHK2 [12];  Type XI, or Fanconi-Bickel Syndrome, which is caused by accumulation of the gene that encodes glucose transporter GLUT 2 [13];  Type XII, or distal glycogenosis, which results from aldolase A deficiency [14];  Type XIII, which develops due to β-enolase deficiency [15];  Type XIV, which develops due to phosphoglucomutase deficiency [16]; and  Type 0, which develops due to glycogen synthase deficiency [17]. Although MS is caused by the deficiency of a muscle enzyme (myophosphorylase), it affects several organ systems, such as the nervous, cognitive and metabolic ones.…”