Cori disease, also known as glycogen storage disorder type III, is an inherited disorder caused by a defect in the glycogen synthesis mechanism. It belongs to a group of diseases known as glycogen storage diseases.
What are glycogen storage diseases?
Our cells require glucose to provide energy for basic life activities. Since we do not eat constantly, our body is required to adjust to temporary shortages in glucose. To store glucose for times of need, different cells synthesize glycogen – a long, branched molecule consisting of long glucose chains.
In times of glucose shortage in the body, certain enzymes break down glycogen, release the glucose, and transfer it to the bloodstream, where it can supply energy to various tissues. Impairments to the glycogen metabolism process cause various disorders known as “glycogen storage diseases”.
The genetic basis of Cori disease
Part of the glycogen breakdown process includes a gradual removal of glucose molecules from the glycogen chain. The enzyme phosphorylase is responsible for releasing the glucose molecules.
Before this enzyme can become activated, other enzymes must first open the glycogen chain and remove branching points. These actions are vital to the glycogen breakdown process and are performed by a debrancher enzyme. In Cori disease, the gene coded to this enzyme is mutated.
The mutated gene, called AGL, is located on chromosome 1. This same gene is coded to an enzyme found in various tissues, but different protein production processes create different enzyme products in the muscle and heart.
Several gene mutations were found to cause this disease. The prevalence of a certain mutation is higher in the Faroe Islands (a small group of islands between Scandinavia and Iceland). In addition, another mutation is more frequent in people of North African Jewish descent (around 1 in 5,400 people in this ancestry group are affected). The general prevalence of GSD3 is 1 in 100,000 people, which makes it a rare disorder.
Signs and symptoms
Symptoms of Cori disease take different forms and have various levels of severity. The disease can cause damage to the muscles, the liver, or both. People with this disease develop an enlarged liver (caused by the accumulation of glycogen in the cells), and hypoglycemia (low blood sugar).
Other symptoms include short stature, decreased muscle tone, and muscle weakness (also called myopathy) – a symptom that is dominant in adult patients and has a profound effect on their quality of life.
How is the disease diagnosed?
Traditional diagnosis is based on high levels of the enzyme creatine kinase, detected via a blood test. Genetic testing can also be used to confirm the diagnosis, especially when the mutation is known to run in the family, or when there is a risk for a certain mutation that can be screened for.
Prenatal genetic screening is recommended in cases of a family history of GSD3, or when both parents are of ethnic descent groups known to be at an increased risk.
Treatment
Unfortunately, there is no specific treatment for Cori disease. The glycogen dysfunction can be dealt with by frequent meals containing starch (a polymeric carbohydrate found in plant-based foods, like glycogen). In addition, Patients can most likely benefit from a high-protein diet.
