What We Learned at the First World CDG Conference in Barcelona

After the conference, new facts and interesting ideas swilled around in my head like the fish that could have happily fitted into my extra-large-post-conference-day-one gin and tonic glass.

Here’s what I can make of my notes…

Half of our proteins need ‘sugar trees’ to form on the outside of them, and when these trees, or glycans, are incomplete, this causes CDG. Different gene mutations can cause a range of types of CDG, and because the mother and the father both give a different gene mutation (genotype), the effects on each child (phenotype) can vary dramatically, even in the same type of CDG. This is called a ‘glycophenotype’. For example, the L32R mutation is associated with milder CDG.

Finnan has PMM2-CDG and it’s only called PMM2 because another PMM was named first, on chromosome 22. So PMM2 was the name for the gene on chromosome 16.

From January to June in 2013, 10 new sub-types of CDG were discovered- that’s one every 18 days on average. New technology can weigh the mass of the sugar trees and scientists can accurately determine which type of CDG a person has. There are two main types of CDG- CDG 1 and CDG 2. The type Finnan has- CDG 1a, is the most common.
Some diseases, such as multiple exostoses and tumoral calcinosis, are now known to be EXT-CDG and GALNT3-CDG respectively. There are most certainly other diseases that are actually types of CDG.

CDG is a multi sub organelle disease, which means that it is found in many parts of the cell, not just in one place. It is possible to create the correct protein the cell needs, but it is currently impossible to get it into the right places in the cell without it being toxic.

It is important that testing takes place early on when CDG is suspected. This is because the main testing method involves analyzing transferrin (by a process called Isoelectrofocusing of transferrin or IEF using High Performance Liquid Chromatography or HPLC), has shown that transferrin normalises in about 75% of adult cases.

Both main types of CDG, CDG 1 and CDG 2, cause damaging affects to the brain before birth, causing the cerebellum to be smaller than normal. The only case where this is not true is CDG 1b, and this type of CDG is the only treatable one.
In Brazil, 2619 people who showed symptoms were tested and 32 were found to have CDG. There were 26 CDG 1 types and 6 CDG 2 types.

In addition, 19 adults with cerebellar ataxia were tested and 1 was found to have CDG 1a. This patient was 32 when they were diagnosed. Local authorities lost contact with her after her family moved out of the city due to her brother being a drug dealer 🙁

In Spain, there are 79 confirmed cases of CDG and 42 pending investigations. 75% of these confirmed cases are alive and 30% of them are adults.

In Italy, there are 16 ‘classic’ cases aged 7 to 38 yrs and 14 ‘mild’ cases aged 3 to 67 years. The distinction between ‘classic’ and ‘mild’ in Italy is based on the difference in cerebellum size. 80% of the ‘mild’ cases can walk.
In Bulgaria, there are 144 cases of CDG. One of the most common types is GNE-CDG, which is of gypsy origin.

In the Czech Republic, there are 74 CDG cases.

The UK was not represented at the conference and we do not know the statistics on CDG in the UK.

(Russia has no confirmed cases at all, which surprised some professionals. And actually surprises me too, because my blog’s stats show that Russia is the 4th highest country for post hits. Hello Russia!)

France has 158 confirmed cases after 40,000 samples were tested there. 46 of these were done prenatally.
Quatar has a handful of cases of CDG 1a, which was previously diagnosed as PKU.

There is no agreement between countries about how to classify the severity of CDG, but the Nijemegen paediatric CDG rating scale, designed in the Netherlands seems to be a good solution to this problem.

A lovely, family friendly doctor called Dr Marc Patterson, a Professor of Neurology in the USA, explained some of the terms like ataxia, and pukinje cells to us (damaged in the cerebellum of CDG patients). He explained one of our mysteries- why our children are so strong, but can’t bear weight on their arms or legs- he said it was because the damage to the cerebellum that had happened before birth meant that they did not have the coordination or balance to walk. Their bodies weren’t programmed for it. We asked him why our children were relatively dexterous with their hands but would misjudge when reaching for an object. Apparently the left and right die of the brain also deal with hand coordination explaining their good hand skills, but again, the cerebellum was to blame for the jerky, off target arm movements.

Dr Jaeken said that in CDG research ‘the rewards are many, but the workers are few’, and he summed up by saying that there should be more collaboration between scientists, politicians and patients, better screening, better understanding of pathogenesis (whatever that is), and more efficient treatments.