Glycogen Storage Diseases

Overview :

Most of the body's cells rely on glucose as an energy source. Glucose levels in the blood are very stringently controlled within a range or 70-100 mg/dL, primarily by hormones such as insulin and glucagon. Immediately after a meal, blood glucose levels rise and exceed the body's immediate energy requirements. In a process analogous to putting money in the bank, the body bundles up the extra glucose and stores it as glycogen in the liver and muscles. Later, as the blood glucose levels begin to dip, the body makes a withdrawal from its glycogen savings.

The system for glycogen metabolism relies on a complex system of enzymes. These enzymes are responsible for creating glycogen from glucose, transporting the glycogen to and from storage areas within cells, and extracting glucose from the glycogen as needed. Both creating and tearing down the glycogen macromolecule are multistep processes requiring a different enzyme at each step. If one of these enzymes is defective and fails to complete its step, the process halts. Such enzyme defects are the underlying cause of GSDs.

The enzyme defect arises from an error in its gene. Since the error is in the genetic code, GSDs can be passed down from generation-to-generation. However, all but one GSD are linked to autosomal genes, which means a person inherits one copy of the gene from each parent. Following a Mendelian inheritance pattern, the normal gene is dominant and the defective gene is recessive. As long as a child receives at least one normal gene, there is no risk for a GSD. GSDs appear only if a person inherits a defective gene from both parents.

The most common forms of GSD are Types I, II, III, and IV, which may account for more than 90% of all cases. The most common form is Type I, or von Gierke's disease, which occurs in one out of every 100,000 births. Other forms, such as Types VI and IX, are so rare that reliable statistics are not available. The overall frequency of all forms of glycogen storage disease is approximately one in 20,000-25,000 live births.