Congenital Disorders of Glycosylation (CDG), formerly called carbohydrate-deficient glycoprotein syndrome, are a group of inherited disorders that affect a process called glycosylation.
Glycosylation is a process by which all human cells build long sugar chains that are attached to proteins. Together the proteins and their attached sugars are called glycoproteins. Glycoproteins, have many very important functions in the human body and are required for the normal growth and function of all tissues and organs. The process or pathway which makes this glycosylation takes at least 100 steps, and specialized proteins called enzymes trigger each step. Hundreds of enzymes are used in making the sugar chains and adding them to thousands of proteins. Sometimes coordinated groups of enzymes work in a specific order to add some sugars, or cleave others from the maturing chain. In individuals born with CDG, one of the many glycosylation enzymes in the pathway malfunctions. However, the impact on the body structures and functions differs depending upon the altered enzyme. CDG is caused by a genetically inherited change or malfunction of one of these enzymes. If one of these enzymes malfunction then the cells in the body of a child or adult cannot glycosylate correctly. This incorrect glycosylation is the underlying basis of the important medical issues in individuals with CDG.
Types of CDG
Scientists investigating CDG (who are called glycobiologists) have identified 19 types of CDG each with its own unique defective enzyme identified. Most of the glycosylation disorders have been identified in the synthesis of N-linked oligosaccharides. These oligosaccharides are assembled in a specific order to create different sugar chain patterns on proteins in every cell. Because of the important biologic functions of these oligosaccharides for protein stability and cell communication, incorrect synthesis may result in clinical problems in different organs of the body. The very complexity of sugar chain assembly practically guarantees that more gylcosylation disorders will be discovered.
While CDG is a rare disease, a great deal of new scientific information indicates that it may be more common than originally thought. There are approximately 500 cases of all types of CDG worldwide, it is probably only a few percent of the total patients. It is safe to say that the entire group of CDGs is severely underdiagnosed. CDG patients are often misdiagnosed early on because their symptoms resemble other generic disorders. CDG-Ia patients are sometimes mistaken for having inherited mitochondrial disorders or ataxic cerebral palsy.
Current research aimed at "boosting" glycosylation pathways are under development in cellular models. However, it is hoped that a stimulation of glycosylation at the cellular level may eventually compensate for defects and restore normal glycosylation levels. New research has identified several types of CDG and is focused on both the causes and possible treatments for this condition as well as appropriate medical management of children and adults affected with these disorders.