From the Guidelines
Cori disease, also known as glycogen storage disease type III (GSD III), is a rare genetic disorder caused by a deficiency of the glycogen debranching enzyme, leading to accumulation of abnormal glycogen in the liver, muscles, and heart. The pathophysiology of Cori disease involves the inability to completely break down glycogen during periods of fasting, resulting in hypoglycemia and accumulation of limit dextrin, an abnormal form of glycogen with short outer branches 1. This accumulation causes a range of clinical symptoms, including hepatomegaly, elevated liver enzymes, and impaired glucose release during fasting in the liver, as well as progressive weakness, cardiomyopathy, and exercise intolerance in muscles.
Key aspects of the pathophysiology of Cori disease include:
- Inability to break down glycogen due to deficient glycogen debranching enzyme activity
- Accumulation of abnormal glycogen (limit dextrin) in the liver, muscles, and heart
- Hypoglycemia and impaired glucose release during fasting
- Hepatomegaly and elevated liver enzymes due to glycogen accumulation in the liver
- Progressive muscle weakness, cardiomyopathy, and exercise intolerance due to glycogen accumulation in muscles
The clinical presentation of Cori disease typically includes hypoglycemia, growth retardation, and hepatomegaly in childhood, with muscle symptoms becoming more prominent later in life 1. The underlying genetic cause is mutations in the AGL gene, which is inherited in an autosomal recessive pattern. Understanding the pathophysiology of Cori disease is crucial for managing the condition, including the need for frequent carbohydrate-rich meals to prevent hypoglycemia and the potential benefits of medium-chain triglyceride supplementation as an alternative energy source.
From the Research
Pathophysiology of Cori Disease
The pathophysiology of Cori disease, also known as Glycogen Storage Disease Type III (GSDIII), is characterized by a deficiency in the glycogen debranching enzyme, amylo-1,6-glucosidase,4-alpha-glucanotransferase (AGL) 2, 3, 4, 5. This deficiency leads to the accumulation of abnormally structured glycogen in tissues, resulting in variable organ dysfunction.
Key Features of GSDIII
- Deficiency in AGL enzyme, leading to impaired glycogenolysis 2, 3, 4
- Accumulation of limited dextrin in tissues, causing organ dysfunction 2, 3
- Clinical presentation includes hepatomegaly, hypoglycemia, hyperlipidemia, and increased CK levels 2, 3
- Disease onset typically occurs in early childhood, with hepatomegaly being the most common presenting clinical sign 2, 3
Molecular Basis of GSDIII
- Mutations in the AGL gene, including nonsense, frameshift, and missense mutations, can lead to GSDIII 3, 4
- The C-terminal region of the AGL protein is responsible for binding to glycogen, while the N-terminal region possesses separate domains for transferase and glucosidase activities 4
- Mutations in the carbohydrate-binding domain (CBD) of AGL can lead to significant loss of enzymatic activities and carbohydrate binding ability 4