Research into Congenital Disorders of Glycosylation (CDG)

Why does CDG occur?

Testing for CDG

The Future for CDG

What can you do to help?

Is there a treatment for CDG?

Why does a Congenital Disorder of Glycosylation occur?

A Congenital Disorder means the disorder is present from birth.  Congenital Disorders of Glycosylation (CDG) is an inborn error of metabolism.  It is mostly a recessive hereditary genetic disorder. There are approximately 1000 diagnosed cases worldwide.

Glycosylation is the process in which sugar trees (glycans) are attached to proteins in a specific order. These are called glycoproteins and are vital for the development of healthy cells and, therefore, the body’s healthy growth and development.

The initial test for CDG is a blood test to look for abnormalities in the transferrin pattern.  Errors in the transferrin pattern results in a type I or type II CDG.

“The transferrin protein carries two ‘glyco’-trees, each having two branches in most of the cases.  In CDG type I, one or both of the trees are completely missing.  In CDG Type II, the base of the tree is present, but something happened to the branches” Mailys Guillard, Biomedical Engineer

Sugar ‘trees’ or ‘chains’ are very important for the proper function of the body’s proteins. Problems with the sugar trees (glycans) being absent or incomplete interferes with the proper function of the proteins.  Proper cell function, as well as good cell to cell communication, is very important, as it regulates the activity and function of enzymes, hormones, and proteins in the body.  This is needed for good health, growth and development. 

When there is an error in the glycosylation process, this can have serious consequences throughout the entire body.  Symptoms can range from mild to severe.  But CDG can significantly affect growth and development of the brain, as well as the development of speech, language, vision and hearing, and a failure to thrive (growth).   It can also affect organs such as heart, liver and kidneys.

PMM2 is the most well-known CDG.

SLC35A2-CDG is the first CDG to be discovered that is not inherited, but is a spontaneous mutation.

Testing for Congenital Disorders of Glycosylation

Transferrin testing does not always show as abnormal, so more specialist testing is required to either confirm or rule out CDG. 

Transferrin can also normalise over time.  Research has shown that normalisation in transferrin levels can miss a diagnosis for CDG.  Because Transferrin testing does not always show as abnormal, more specialist testing is required to either confirm or rule out CDG. The earlier testing for CDG is carried out, the better the chances of diagnosis.  The liver’s function can normalise over the years; which will affect the test results of the Isoelectric focussing of transferrin serum.  In these cases, further specialist testing is needed to either confirm or rule out a diagnosis of CDG.

“Type I and Type 2 classification is becoming a little more difficult now, because not all genes that should give a Type I or type II affect Transferrin.  While Transferrin is useful, it is not a guarantee to be abnormal.”  Bobby Ng, Sanford Burnham, 5 May 2017

Advances in the field of genetics shows that the discovery of new CDG is growing very rapidly.  It is expected that many different CDG will be discovered/detected in the future.

The important thing to remember is that if a child presents with symptoms such as developmental delay, organ failure and failure to thrive, then to suspect CDG.  Many tests are already available as standard to test for unexplained developmental delays in children.  There needs to be more awareness of CDG amongst the medical practitioners, so that testing for CDG happens too.

Research is vital to diagnosing CDG.  With the knowledge Sanford Burnham Medical Research Institute has gained through the discovery of three different CDG: SLC35A2-CDG, ALG13-CDG and SSR4-CDG, which are all spontaneous mutations, it is important that a combination of genetic and biochemical diagnoses are used.

Brain function is involved in most CDG.  Proper brain development is crucial early in foetal development.  CDG can affect the development of the brain and leave those affected by CDG with physical, neurological and learning difficulties, as well as medical complications involving the internal organs, such as heart, liver and kidneys.  Brain tissue does not repair itself like the liver cells can.  It is difficult to approach the brain with any treatment as brain development is already affected by the time an affected child is born. Impaired development of, or damage to the brain, cannot be reversed or treated.  Treatments may make the body healthy but you cannot, unfortunately, fix the brain if impaired development or damage is already evident.  Professor Jaak Jaeken refers to this as “sugar tragedies” in his video below:

The Future for CDG

Jaak Jaeken sums this up perfectly by saying:

  • More awareness and research!!!!
  • More collaboration between scientists, patients, politicians.
  • Better screening.
  • Better understanding.
  • Efficient treatments.
  • Courage and perseverance.

What can you do to help?

Join the patient registries
When it comes to research in the world of a rare disease, sample size is everything, and engaging patients and their families is crucial.

A registry is a collection of data giving standardised information about a group of patients. We need to learn about normal variation in CDGs, how they progress over time, whether lab results are stable, and crucially, what we actually need to measure (the best biomarkers). The more information we have about CDGs, the better we can understand their causes and effects. The more we know about their causes and effects, the more we can research into potential therapeutic treatments. Therefore, signing up to a patient registry is a must.

Below is a list of patient registries available for CDG patients to contribute to. You may wonder why we don’t just have one registry for all patients, and that is a valid question! Unfortunately, there is fragmentation of data sources across Europe- there is very little sharing due to data protection and ownership rights. All registries should make it clear to you exactly what will happen to your data, how it will be stored, and who it will be shared with. You will need to give your consent for each registry. 

CDG Connect: this registry is run by CDG Care USA and is open to European patients too. It is designed to be patient friendly, and there are 5 surveys to complete. The registry is secure and free, not overly time consuming, and its patients and families who own the data.

Unified Registry for Inherited Metabolic Disorders (UMID): This is a European registry which includes CDG. The aim of this registry is to unify data and information about all inherited Metabolic Disorders across Europe. Your doctor will need to sign up to this one and fill in the forms, although there are some questionnaires for patients, the answers of which your doctor will need to input. To encourage your doctor, download the leaflet from, and take it along to your next appointment. 

National Institute of Health Natural History Study: Lynne Wolf C.R.N.P. is the principle investigator for this natural history study of CDGs, which is now in its 6th year. A natural history study collects clinical and biological data about patients which is then used for research. This study involves a trip to Washington DC (once you get to the USA, everything else is government funded and free) and a week at a hospital.

Glycomine’s Natural History Study: This is a new study for PMM2-CDG patients, run by Glycomine, Inc, a private lab in California. Some NIH sites are used to collect data. The closest location currently available is in France, and the details can be found at

EuroBioBank: A network of biobanks in Europe that store and distribute quality DNA, cell and tissue samples for scientists conducting research on rare diseases. There are currently 25 biobanks in 11 European countries, including sites in London and Newcastle.

Prognosis for Congenital Disorders of Glycosylation


Glycomine, a research lab in the USA, is researching how to transport the PMM2 enzyme through the cell membrane and into the cell as a therapeutic treatment. It is extremely important to remember that this idea is a worthy approach for PMM2; but it’s really years away from use. 

Other researchers are looking at drug re-purposing. This means that a drug that is already on the market for another condition could have beneficial effects for CDG patients. Research shows that there is some evidence a Japanese drug, epalrestat, used for adult peripheral neuropathy, improves PMM2 enzyme activity.

Studies are ongoing, but it will be several years before clinical trials on patients will happen. You can read a scientific paper on this research here.


“Mannose looks good for these patients.”


“Galactose – Only one paper claims an effect and that is only on transferrin.  No clinical improvement.”


“Galactose – there appears to be some benefit.  That looks good.”

Source: Pr.Hud Freeze, Director of the Human Genetics Program at Sanford Burnham Medical Research Institute, 14th June 2017

Let’s further CDG research together!

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