8.3 Glycogen storage diseases

While the above reactions should account for the complete degradation of glycogen (except for the very last glucose residue attached to glcyogenin), there is more than meets the eye. This is evident from the fact that a genetic defect in an apparently unrelated enzyme—lysosomal maltase, which cleaves the α1→4-glycosidic bond between two glucose residues¹—causes the accumulation of glycogen in all kinds of tissues, with particularly detrimental consequences in heart muscle. The accumulation of glycogen 'pudding' inside the cell interferes with cell motility and therefore with the contraction of the heart, and heart failure leads to death. The condition is known as Pompe's disease.

Other enzymes may be deficient as well. A deficiency of phosphorylase in the muscle is known as McArdle's disease; patients suffer from rapid exhaustion and muscle pain during exertion. A defect of glucose-6-phosphatase is mostly manifest in the liver and kidney. It will affect the release of glucose from glucose-6-phosphate formed by both glycogen degradation and gluconeogenesis, which in turn leads to critically low blood glucose (hypoglycemia).

1: The reaction is the same as catalyzed by the brush border maltase in the degradation of amylose; however, the lysosomal enzyme is a separate entity and has an acidic pH optimum, in keeping with the acidic environment inside the lysosomes.