Biochemistry and molecular genetics of human glycogenoses
Abstract
Most of the glycogen metabolism disorders that affect skeletal muscle involve enzymes of glycogenolysis (myophosphorylase ( PYGM ), glycogen debranching enzyme ( AGL ), phosphorylase b -kinase ( PHKB )) and glycolysis (phosphofructokinase ( PFK ), phosphoglyceromutase ( PGAM 2), aldolase A ( ALDOA ), β -enolase ( ENO 3)); however, 3 of them involve glycogen synthesis (glycogenin-1 ( GYG 1), glycogen synthase ( GSE ), and debranching enzyme ( GBE 1)). Many present with exercise-induced cramps and rhabdomyolysis with more intense exercise (ie, PYGM , PFK , PGAM 2), while others present with muscle wasting and weakness ( GYG 1, AGL , GBE 1). Failure of serum lactate to rise with exercise, with an exaggerated response to ammonia, is a common but not invariant feature. Serum creatine kinase ( CK ) levels are often elevated in myopathic forms and PYGM deficiency , but may be normal and elevated only in rhabdomyolysis ( PGAM 2, PFK , ENO 3). Therapy for glycogen storage diseases that result in exercise-induced symptoms involves lifestyle adaptations and carefully selected exercises. Immediate carbohydrate ingestion before exercise improves symptoms in glycogenolytic defects (i.e., PYGM), but may worsen symptoms in glycolytic defects (i.e., PFK ). Low-dose creatine monohydrate may provide modest improvement in PYGM mutations.