Glycogen Storage Diseases

GSD are a group of genetic diseases caused by defects in enzymes required for glycogen degradation or, more rarely, glycogen synthesis. They result either in formation of glycogen that has an abnormal structure or in the accumulation of excessive amounts of normal glycogen in specific tissues as a result of impaired degradation.

A particular enzyme may be defective in a single tissue, such as the liver (resulting in hypoglycemia) or muscle (causing muscle weakness), or the defect may be more generalized, affecting a variety of tissues, such as the heart and kidneys. Severity ranges from fatal in early childhood to mild disorders that are not life threatening. Some of the more prevalent GSD are illustrated in Figure 1. [Note: Only GSD II is lysosomal because glycogen metabolism occurs primarily in the cytosol.]

Figure 1: Glycogen degradation, showing some of the glycogen storage diseases (GSD). [Note: GSD type IV: Andersen disease is caused by defects in branching enzyme, an enzyme of synthesis, resulting in liver cirrhosis that can be fatal in early childhood.] Pi = inorganic phosphate; P = phosphate.