GENETIC DEFECTS OF GLYCOGEN METABOLISM AND ITS CONTROL

Genetic defects of glycogen metabolism are known in man, dog, mouse and in bacteria. In 2 of the human glycogen storage diseases the symptoms are related to the glycogen accumulation itself (lysosomal α glucosidase and branching enzyme deficiency). All other human glycogen diseases are primarily triggered by a shortage of glucose or glycolytic intermediates (deficiencies of glucose 6 phosphatase liver or muscle phosphorylase, phosphorylase kinase or debranching enzyme). Three of the defects should in fact be considered inborn errors in control of metabolism, since they are not defects of enzymes of glycogen metabolism itself. These defects are deficiency of phosphorylase kinase, glucose 6 phosphatase and phosphofructokinase. In the latter 2 the glycogen accumulation is secondary and caused by increased availability of substrate (glucose 1 phosphate) as well as stimulatory action of elevated glucose 6 phosphate concentrations on the glycogen synthase system. Phosphorylase kinase deficiency may be caused by an increase of the Km of the enzyme for its macromolecular substrate or by a decrease in the total amount of enzyme present. A large proportion of heterozygotes of this X linked deficiency show some signs of their defect especially at an early age.