FAQ

Congenital disorders of glycosylation (CDG) are a group of rare genetic diseases that affect the process of adding chains of sugar “building blocks”, called glycans, to proteins and fats (lipids) in cells throughout the body. This process is called glycosylation and is important for healthy functioning of all tissues and organs. CDG causes problems in the ways that glycans are attached to proteins and fats, resulting in a variety of symptoms, potentially affecting multiple organs.

Glycans are sometimes called “sugar trees” or “sugar chains”. They are built from sugar “building blocks”. Glycans are needed for different types of proteins and lipids to work properly in the body. Glycosylation is the process of creating, changing and attaching these sugar building blocks to proteins and lipids. When glycans are attached to proteins, they are called glycoproteins and when glycans are attached to lipids, they are called glycolipids.

Defects in glycosylation can cause the incorrect glycans to be attached to proteins and lipids, or glycans to be missing completely, causing CDG. As glycosylation is needed for different proteins and lipids to work properly throughout the body, faults in glycosylation can impact multiple organs, causing a wide variety of symptoms in individuals with CDG. While glycosylation involves sugar molecules, CDG is not related to diabetes as glycans are not used as an energy source.

CDG are genetic disorders, meaning that in most cases, they are inherited from an individual’s parents. We inherit pairs of genes, one from each of our parents. Our genes make each of us unique, as they contain the instructions required for the body to maintain its complex processes. CDG is caused by faults, called mutations, in genes that have a role in glycosylation. Over 400 different genes are involved in glycosylation and mutations in over 160 of them have been found to cause different types of CDG.

To date, over 1500 people have been diagnosed with CDG but because CDG are often mis- or underdiagnosed, it is likely that there are many more affected individuals.

As of 2021, more than 160 different CDG types have been identified. New CDG types are regularly identified through genetic testing. A list of all CDG types identified to date and how they may be classified can be found here.

CDG are classified and named according to the affected gene. For example, CDG caused by mutations in the PMM2 gene are called PMM2-CDG. CDG may also be broadly classified into categories according to the glycosylation pathway(s) that is affected. Major categories include disorders of N-glycosylation, disorders of O-glycosylation, disorders of lipid (glycosphingolipid) and GPI-anchor glycosylation, and disorders of multiple glycosylation pathways.

The first CDG was discovered in 1980 by Jaak Jaeken and colleagues, and the specific type was caused due to mutations in the PMM2 gene. Initially, this was termed “carbohydrate deficient glycoprotein syndrome” however upon discovery of many more disorders caused by defects in glycosylation, these were renamed to “congenital disorders of glycosylation”. PMM-CDG was also formerly called CDG-1a.

PMM2-CDG is the most common CDG, with more than 1000 reported patients.

Symptoms vary greatly depending on the CDG type and even among individuals with the same type or affected individuals from the same family. Although CDG can result in problems with many of the body’s organs and systems, neurological symptoms are common among many CDG types. Common neurological symptoms include diminished muscle tone (hypotonia), seizures, intellectual disability, developmental delay, stroke-like episodes and problems with balance and coordination (ataxia). Other common symptoms include growth problems (failure to thrive), liver disease, and problems with bleeding and blood clotting.

Symptoms vary greatly depending on the CDG type and even among individuals with the same type or affected individuals from the same family. Although CDG can result in problems with many of the body’s organs and systems, neurological symptoms are common among many CDG types. Common neurological symptoms include diminished muscle tone (hypotonia), seizures, intellectual disability, developmental delay, stroke-like episodes and problems with balance and coordination (ataxia). Other common symptoms include growth problems (failure to thrive), liver disease, and problems with bleeding and blood clotting.

As symptoms of CDG are often present in infancy and childhood, individuals may be diagnosed when they are very young. However, because symptoms of CDG are similar to other disorders, individuals are often initially misdiagnosed with different conditions resulting in a delay of an accurate diagnosis. Additionally, because some CDG types are so rare, it is thought that many people remain undiagnosed or misdiagnosed.

Few CDG have specific treatment options available therefore treatment is primarily focused on managing specific symptoms to improve quality of life.  Some CDG may be treated by nutritional supplementation where specific substances that are at low levels, such as certain sugars, are supplemented in the diet.

While children with CDG often tend to be cheerful and social, symptoms and their severity vary greatly across individuals and as such, every CDG child will have a unique set of needs. Most children with CDG will need a team of medical specialists, as well as a multi-disciplinary support system that can provide personalized care. The need for certain specialists may change as health conditions evolve over time. Depending on the severity of their symptoms, some children may require frequent and lengthy hospitalizations. However, the frequency of critical episodes usually decreases gradually as children grow older. While many children with CDG deal with cognitive and physical disabilities, their quality of life may be greatly improved with physical, occupational and speech therapy.

There have been cases of individuals with CDG contracting COVID-19, with disease severity ranging from asymptomatic (no symptoms) to severe. However, individuals with CDG are currently thought to be at a similar risk to severe forms of COVID-19 disease as healthy individuals who are of a similar age.

The recommendation by the CDG experts of the Frontiers in CDG Consortium (FCDGC) is for CDG patients, parents and caregivers to be vaccinated against COVID-19. Read the official vaccination recommendation by the FCDGC here.

You can learn more about CDG and COVID-19 and frequently asked questions by watching the informational webinar developed by the FCDGC here.