glycogen storage disease type III Approximately 100 mutations in the AGL gene have been found to cause glycogen storage disease type III (also called GSDIII or Cori disease). Most of these mutations lead to a premature stop signal in the instructions for making the glycogen debranching enzyme, resulting in a nonfunctional enzyme. As a result, the side chains of glycogen molecules cannot be removed and abnormal, partially broken down glycogen molecules are stored within cells. A buildup of abnormal glycogen damages organs and tissues throughout the body, particularly the liver and muscles, leading to the signs and symptoms of GSDIII. Mutations in the AGL gene can affect different isoforms of the enzyme, depending on where the mutations are located in the gene. For example, mutations that occur in a part of the AGL gene called exon 3 affect the isoform that is primarily expressed in the liver. These mutations almost always lead to GSD type IIIb, which is characterized by liver problems.

     The AGL gene provides instructions for making the glycogen debranching enzyme. This enzyme is involved in the breakdown of a complex sugar called glycogen, which is a major source of stored energy in the body. Glycogen is made up of several molecules of a simple sugar called glucose. Some glucose molecules are linked together in a straight line, while others branch off and form side chains. The glycogen debranching enzyme is involved in the breakdown of these side chains. The branched structure of glycogen makes it more compact for storage and allows it to break down more easily when it is needed for fuel. The AGL gene provides instructions for making several different versions (isoforms) of the glycogen debranching enzyme. These isoforms vary by size and are active (expressed) in different tissues.

The following transcription factors affect gene expression:

• Max
• STAT3

Tissue specificity:

Liver, kidney and lymphoblastoid cells express predominantly isoform 1; whereas muscle and heart express not only isoform 1, but also muscle-specific isoform mRNAs (isoforms 2, 3 and 4). Isoforms 5 and 6 are present in both liver and muscle.

Molecular Function:

• 4-Alpha-Glucanotransferase Activity
• Amylo-Alpha-1,6-Glucosidase Activity
• Glycogen Debranching Enzyme Activity
• Polysaccharide Binding

Biological Processes:

• Glycogen Biosynthetic Process
• Glycogen Catabolic Process
• Response To Glucocorticoid
• Response To Nutrient