Myopathies Related to Glycogen Metabolism Disorders

Abstract

Most of the glycogen metabolism disorders that affect skeletal muscle involve enzymes in glycogenolysis (myophosphorylase (PYGM), glycogen debranching enzyme (AGL), phosphorylase b kinase (PHKB)) and glycolysis (phosphofructokinase (PFK), phosphoglycerate mutase (PGAM2), aldolase A (ALDOA), β-enolase (ENO3)); however, 3 involve glycogen synthesis (glycogenin-1 (GYG1), glycogen synthase (GSE), and branching enzyme (GBE1)). Many present with exercise-induced cramps and rhabdomyolysis with higher-intensity exercise (i.e., PYGM, PFK, PGAM2), yet others present with muscle atrophy and weakness (GYG1, AGL, GBE1). A failure of serum lactate to rise with exercise with an exaggerated ammonia response is a common, but not invariant, finding. The serum creatine kinase (CK) is often elevated in the myopathic forms and in PYGM deficiency, but can be normal and increase only with rhabdomyolysis (PGAM2, PFK, ENO3). Therapy for glycogen storage diseases that result in exercise-induced symptoms includes lifestyle adaptation and carefully titrated exercise. Immediate pre-exercise carbohydrate improves symptoms in the glycogenolytic defects (i.e., PYGM), but can exacerbate symptoms in glycolytic defects (i.e., PFK). Creatine monohydrate in low dose may provide a mild benefit in PYGM mutations.

Keywords: Glycolysis; forearm exercise test; glycogenolytic; glycogenosis; myogenic hyperuricemia.

Fig. 1

Electron microscopy of human skeletal muscle. IMCL = intramyocellular lipid; IMF = intermyofibrillar; SS = subsarcolemmal

Fig. 2

Glycogen metabolism in skeletal muscle. GLUT = glucose transporter; DHAP = dihydroxyacetone phosphate; GYS1 = glycogen synthase; BE = branching enzyme; MCT = monocarboxylate transporter; TCA = tricarboxylic acid cycle.