The history of CDG

What is the history of CDG?

The disorders described in this Congenital Disorders of Glycosylation (CDG) timeline below are known to affect the N-glycosylation pathway.  There are a large number of other glycosylation disorders, which are not mentioned; but we are aware of them.  The following link explains many of the known CDG:

“Congenital Disorders of Glycosylation are a group of more than 60 mainly autosomal recessive disorders caused by impaired synthesis of glycoconjugates.  Affected individuals often have profound neurological deficiencies, including intellectual disability, seizures, and a wide range of multi-organ symptoms.  The majority of CDG defects involve the N-linked glycosylation pathway, and alterations can be detected by abnormal glycosylation of the convenient biomarker serum transferrin.” The American Journal of Human Genetics 92, 632-636, April 4, 2013

Glycoconjugates are carbohydrates (sugars) linked to a protein or lipid (fat). These are known as glycoproteins and glycolipids.

When was CDG discovered?


Professor Jaak Jaeken MD

The first CDG case was discovered by Professor Jaak Jaeken MD, and colleagues; one of whom was Henk Van Eiyk; a blood specialist from Rotterdam who had a particular interest in iron and its transportation through the blood.  This first case involved twin sisters, who were aged 1 ½ years old at the time.  They had various medical issues including fluctuating hormone levels, a psychomotor disability and atrophy (diminished intellect and brain function.)  Henk Van Eiyk had already produced a paper on Isoelectric Focussing of Serum Transferrin.  It was this test which enabled the girls’ blood to be screened for any metabolic abnormalities.  These abnormalities showed a problem with the girls’ glycosylation. 

At the time it was not known that “it was the absence of entire sugar chains.  That fact came along later and was very important in figuring out the problems”.  From email communication with Hud Freeze (Sanford Burnham Medical Research Institute, California) dated 28.06.2017


The results of this isoelectric focussing of Transferrin test were published.


Professor Jaeken contacted Helena Stibler; a neurologist from Stockholm.  Her interest was in investigating chronic alcoholism in adults.  This is a condition which also shows abnormalities in the body’s transferrin levels.  The liver is responsible for the metabolism of alcohol as well as the filtration and storage of nutrients in the body; one of which is iron. Jaeken contacted Stibler who was able to measure some enzyme samples related to sugar metabolism.  The results found some of Stibler’s patients had a number of characteristics the same as those of the twin sisters that Jaak Jaeken discovered in 1980.  Jaeken and Stibler wrote up their findings and named this disease Carbohydrate-Deficient Glycoprotein Syndromes (CDGS).

Jaeken also met a boy who was aged 10 at the time, from Belgium who presented with a bleeding tooth.  This patient had no speech and language skills, and he could not walk without support.  He also had severe psychomotor delay and epilepsy. Coagulation (blood clotting) investigations showed a decrease in factor 11; a decrease which was also found in the twin sisters back in 1980.  This suggested a similar problem as the twin sisters.  Isoelectric focussing of Transferrin was tested.  The results showed an abnormal transferrin pattern.  But, it was a totally different pattern to that of the twin sisters.  Jaeken named his first case pattern type Ia.  This had an absence in glycan structure.  The second case, which had an abnormality in the glycan structure, was named pattern type IIa. 

“The a and b designations were added because it was beginning to get confusing.  It was only I or II, then somebody wanted III and IV……it would become a problem”. Hud Freeze, Sanford Burnham Medical Research Institute, California, 28th June 2017


Karen Hackney wrote an article in the Research Trust for Metabolic Diseases in Children (RTMDC)’S newsletter about her son Peter, aged 10. At the time of writing CDG was known as Disialotransferrin Developmental Deficiency Syndrome. Peter was 39 when he passed away in 2018 and Karen had never met another family affected by CDG. She made contact with CDG UK in early 2019 and shared the article with us. The RTMDC is now Metabolic Support UK.

You can read an update from Karen here.


“The structural basis of I and II was different but unproven as to cause.  It was work carried out by Wada and Taniguchi that revealed that the sugar chains were missing.” Hud Freeze, Sanford Burnham Medical Research Institute, California, 28th June 2017


Jaak Jaeken shipped samples to Harry Schachter; a Biochemist from Toronto, Canada who was very interested in Jaeken’s request to investigate the samples. Schachter performed the tests in the lab, and Jaeken’s suspicions were correct that it was a type II transferrin deficiency.  There was a defect in the enzyme GlcNAc Transferase II.

“The enzyme assay was very convincing.”  Hud Freeze, Sanford Burnham Medical Research Institute, California, 28th June 2017

In contrast to the type IIa case, the twins, type 1a, had an absence of one or two glycans. Pf. Jaeken suspected a defect very early on in the twins’ glycosylation pathway and enlisted the help of Emile Van Scaftingen.


Emile Van Scaftingen, a biochemist from Louvain- la-Neuve, looked into the twins the glycosylation pathway and found a defect in an enzyme which was not yet known in humans: phosphomannomutase. (PMM) 


Gert Matthijs, a geneticist from Leuven, cloned the PMM gene and found the same genetic mutations in the twins and other patients with the pattern type 1a.  This gene was called PMM2 because the PMM1 gene had already been identified on chromosome 22 by Gert Matthijs and a group of Japanese scientists.

The PMM2 gene deficiency is on chromosome 16.

Isoelectric focussing of transferrin has since become the first diagnostic pathway in testing a patient suspected of CDG.


Niehnes described a new Carbohydrate Deficient Glycoprotein Syndrome 1b; which was caused by mutations in the enzyme phosphomannose isomerase (PMI)


A meeting was held in Leuven between Jaak Jaeken MD, PhD, Hud Freeze PhD; a professor and director of the Human Genetics Program at Sanford Burnham Medical Research Institute in California, Thierry Hennet; a professor of Human Biology at the University of Zurich, and other professionals with an interest in CDG.  The question of the nomenclature was discussed among all participants.

“We were looking for a simpler name than Carbohydrate Deficient Glycoprotein Disorders, that preserved a similar acronym CDGS and linked inheritance to glycosylation.  Shortening Carbohydrate Deficient Glycoprotein Disorder (CDGS) to Congenital Disorders of Glycosylation (CDG) did just that. 

A consensus emerged for Congenital Disorders of Glycosylation.

Each gene was then characterised by a letter following the type I or type II designation.” Hud Freeze, Sanford Burnham Medical Research Institute, California, 13th June 2017


Advances made by JM Lacey, HR Bergen, MJ Magera, S Naylor and JF O’Brien, Clin Chem. 2001 Mar; 47 (3):513-8. PMID: 11238305 shows that…

“Transferrin isoelectric focussing is not used to diagnose all cases. A more precise and informative approach is to use mass spectrometry of serum transferrin. ” Hud Freeze, Sanford Burnham Medical Research Institute, California, 28th June 2017


“The growing number of gene defects identified as causes of CDG prompted the community to abandon the cryptic numbering system….and it was proposed to drop the numbering sequence and simply use the official abbreviation of the mutated gene followed by the letters CDG.  So, CDG1a became PMM2-CDG; given that the PMM2 gene is deficient in this disease.” Thierry Hennet, University of Zurich, 14th June 2017



“This is a mixed type, meaning that is has the transferrin abnormalities typical of BOTH Type I and Type II.  We reported on some of these patients years ago, in 2006, but didn’t know the cause.  In fact, two of them had PGM1 defect and two siblings who had a Type I transferrin pattern also had a newly discovered CDG called TMEM199-CDG.” Pr. Hud Freeze, Director of the Human Genetics Program at Sanford Burnham Medical Research Institute, 28th June 2017


The Rocket Fund, in the United States of America, was set up by John Taylor “Rocket” Williams IV family, when he was diagnosed with Congenital Disorders of Glycosylation. Sadly in November 2008, Rocket passed away. 

“ The Rocket Fund is a place to send money to, where it would be used directly for research into treatments and cures.  With Dr Freeze, we set up the fund so that money could be used by him and his team directly.  After Rocket died, we carried it on, and still raise money for the Fund whenever we can.” Mia Williams; Rocket’s mother.

John Taylor ‘Rocket’ Williams IV

The Rocket Fund remains as a tribute to Rocket and is also an important legacy to CDG research.  His family established the fund at the Sanford Burnham Medical Research Institute in La Jolla, California, to ensure that research into this disorder continues.  Professor Hud Freeze is Director of the Human Genetics Program at Sanford Burnham.

Contribute to The Rocket Fund


The new nomenclature for CDG was adopted. All CDG are now identified and referred to by the defective gene followed by CDG; e.g. CDG 1a is now PMM2-CDG.

“Although this evolution for the new classification seems logical, the path to this change took time.  There was the wider involvement and awareness that needed to be made with medical practitioners, researches and the family network.” Thierry Hennet, University of Zurich, 14th June 2017

This simpler way of recording all the different known CDG easily shows that it is a Disorder of Glycosylation as well as identifying the defective gene.

CDG falls into four different classifications:-

  • Defects in Protein Glycosylation – N Glycosylation
  • Defects in Protein Glycosylation – O Glycosylation
  • Lipid(fats) Glycosylation
  • Combined glycosylation defects and other glycosylation defects.

Learn more about the research behind CDG

July 2011

CDG hearts and hands awareness logo was voted and approved by CDG family members in what was the then active CDG UNITED.  This support group is now known as CDG Global Alliance.


Three unrelated children; two boys; one from England and one from North America and a girl from Canada, were the first diagnosed cases of a new, non-hereditary spontaneous mutation of CDG.  This means that neither parent, nor siblings, carry the affected gene.

Hud Freeze and Bobby Ng at Sanford Burnham Medical Research Institute in California, discovered a new type of CDG:  SLC35A2-CDG.  It is a de novo (meaning new) somatic mosaic mutation (meaning the genetic mutation is not in every cell).  More importantly, this CDG is a spontaneous mutation; neither the parents nor siblings are affected. This is the first case of CDG being spontaneous and not inherited.

The usual diagnostic tests for CDG involving isoelectric-electric focusing of transferrin and whole-exome sequencing missed this mutation.  Transferrin levels which were abnormal in infancy had become normal in early childhood. 

Biochemical methods were used to closer examine the samples and transferrin levels were re-examined.  Where they had previously shown abnormalities, the transferrin levels were now normal.   It is believed that the mutated cells in the children’s liver had died and were replaced by normal cells over time.  However this did not reverse all symptoms and CDG was still evident.  The defective SCL35A2-CDG gene was present in some of the cells; but not all. This is known as a mosaicism.

If Isoelectric Focussing of Transferrin had not be performed early on, then CDG would never have been diagnosed due to the transferrin levels having normalised. 

Isoelectric Focussing of Transferrin cannot be used on its own as a reliable diagnostic tool for CDG as advances in research have shown that this test alone would have missed the fact that these three children have CDG.  It was through further testing that SLC35A2-CDG was confirmed.   It took further diagnostic methods and biochemical testing, including whole-exome sequencing and a fibroblast of skin cultures to finally achieve the full diagnosis of SLC35A2-CDG. 

“It is important to understand that Transferrin isoelectric focussing is not used to diagnose all cases. A more precise and informative approach is to use mass spectrometry of serum transferrin.” Hud Freeze, Sanford Burnham Medical Research Institute, California, 28th June 2017

Read more about types of cell mutation here


In April, the results of this discovery were written up and published in The American Journal of Human Genetics, (volume 92) dated 4th April 2013.

The discovery of this new gene was a 21st century diagnosis and also a medical breakthrough.  It is now known that CDG is not only a hereditary disorder; but that it can be a spontaneous mutation.  It was through the families’ collaboration with their child’s consultants, and through emails and social media with each other and Sanford Burnham Medical Research Institute that these three children were able to finally receive a full diagnosis of SLC35A2-CDG.

In the first half of 2013 (up until June), 10 new different CDG were discovered; one of these was SLC35A2-CDG.  This is not a hereditary CDG but a spontaneous mutation.  It is also a mosaicism; this means that not all cells are affected by this mutation.

World Conference on CDG

1 & 2 September 2013

First World Conference on Congenital Disorders of Glycosylation for families and professionals: “a booming story of sugar trees”, was held in Barcelona, Spain.

26 October 2013

A few CDG families in the UK met up for the first time and agreed to establish a charity in order to help raise awareness of CDG and funds into researching CDG.

World Conferences on CDG are held every 2 years and brings together families and professional from all over the world to learn more about CDG.

Find out about events you can attend

16 August 2014

CDG UK was founded.  Charity constitution was adopted and positions of office and trustees were made.  Our patron is Dr Stephanie Grunewald, Paediatric Consultant in Metabolic Diseases, at Great Ormond Street Children’s Hospital.

29 & 30 August 2015

Second World Conference on Congenital Disorders of Glycosylation for families and professionals: “a challenging story of sugar trees “, was held in Lyon, France.

7 November 2015

CDG UK held its first AGM.

9 November 2015

CDG UK Facebook page was created.  You can receive lots of up to date information via Facebook as well as connecting with other CDG families in the UK.


An online petition to the World Health Organisation (WHO) was created and submitted to WHO by Vanessa R Ferreira of SINDROME CDG in Lisbon, Portugal. The CDG community has requested that WHO acknowledges 16th May as World CDG Awareness Day.  Approval from WHO is still pending (this can take years).  However, family and friends of those touched by CDG will continue to celebrate 16th May as World CDG Awareness Day. 

16th May was chosen as World CDG Awareness Day as this is Jaak Jaeken’s birthday.

16 May 2016

1st World CDG Awareness Day celebrated globally by CDG families and friends. Families across the world wear green and organise fundraising events to help raise awareness of CDG and also vital funds to ensure research into CDG continues.  This is an annual event.

 Why wear green for CDG Awareness Day? 

“Green is an emotionally positive colour, giving us the ability to nurture ourselves and others unconditionally.  This is what CDG families do every day with strength and determination” 

Vanessa R Ferreira

16 May 2017

2nd World CDG Awareness Day celebrated globally by CDG families and friends.

15 & 16 July 2017

Third World Conference on Congenital Disorders of Glycosylation for families and professionals: United shaping the future for CDG”, is to be held in Leuven, Belgium.

5 November 2016

CDG UK second AGM.

15 May 2017

Continued research into CDG is vital.  We now know that there are currently three different CDG which are not inherited, but spontaneous mutations:-

“ALG13-CDG, and SSR4-CDG are also not inherited, but caused by spontaneous mutations just like SLC35A2-CDG” Bobby Ng, Sanford Burnham Medical Research Institute, California

4 November 2017

CDG UK third AGM

26 & 27 July 2019

Fourth World Conference on Congenital Disorders of Glycosylation for families and professionals is held in Portugal

1 March 2020

CDG Family Conference is held in San Diego. You can view clips below:

​18 September 2020

CDG UK is officially listed as a charity!

Registered Charity Number 1191342.

14-16 May 2021

The 5th World Conference on CDG for families and professionals is coming back to Portugal. It will take place on the Science and Technology Faculty of NOVA University of Lisbon, the headquarters of the CDG & Allies Professionals and Patient Associations International Network (CDG & Allies – PPAIN). This next edition theme is #StandUnited4CDG Patient Centric approach that drives CDG therapeutic development: Impossible, Is Possible!”

All the info is here

Make history!

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