What else is it called?
- Carbohydrate Deficient Glycoprotein Syndrome Type Ik
- Congenital Disorder of Glycosylation Type 1k
- Mannosyltransferase 1 Deficiency
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What causes it?
The Congenital Disorders of Glycosylation (CDG) are a group of genetic disorders that have a broad spectrum of symptoms and range from mild to life-threatening in severity. This group is expanding at a rapid pace, and more than 60 different forms of CDG have been reported. Information about the disorders is always changing due to the developments in knowledge and new forms being reported.
The CDGs are caused by defects in one of the body’s natural processes called Glycosylation. This process uses hundreds of different enzymes to allow sugar molecules in the body to attach to certain proteins or lipids (fats). When this happens, they are given the names glycoproteins and glycolipids, respectively. Both are needed to carry out different tasks and are essential for the normal growth and function of the tissues and organs within the body. There are at least 100 steps, all using different enzymes, in the process of glycosylation. If one of the enzymes in the process does not function correctly it can cause a variety of symptoms, affecting many different parts of the body. In this form of CDG, a problem in the ALG1 gene causes an enzyme not work properly.
Previously, the CDGs were broken down into two groups known as CDG-I and CDG 2. However, more recently a new classification has been introduced and now all the CDG’s are listed with the abbreviation of the causative gene followed by “-CDG”
How common is it?
We do not know the exact prevalence. This is a rare disorder. Almost 60 cases have been reported (up to 2017).
What are the signs and symptoms?
Signs and symptoms generally begin in infancy. This is a multisystem disorder, meaning that it affects a number of areas of the body. Symptoms are often severe. However, some people have milder symptoms. You may not have all the symptoms listed below.
Neurological symptoms may include:
- A delay in reaching developmental milestones
- Intellectual disability
- Low muscle tone (hypotonia)
- Co-ordination, balance and speech problems (ataxia)
- Uncontrollable shaking or trembling of one part of the body (tremor)
- Reduced sensation in the limbs (peripheral neuropathy)
Other symptoms may include:
- Blood clotting problems and episodes of bleeding
- Susceptibility to infections and viral illnesses due to poor immunity
- A smaller than average head size (microcephaly)
- Joint problems in which the muscles or tendons have been flexed for too long and cannot be straightened (contractures)
- Longer than average fingers and toes
- Widely spaced eyes
- Involuntary eye movements (nystagmus)
- Crossed eyes (strabismus)
- Small jaw
- Breathing difficulties
- Gastrointestinal problems; diarrhoea and/or an accumulation of protein-containing fluid in the abdomen (ascites)
- Swelling (oedema)
- Enlarged and thickened heart muscle leading to heart problems
- Enlarged liver (hepatomegaly), Liver failure
- Kidney problems
- Enlarged spleen (splenomegaly)
In severe cases, it is unlikely that your child will live beyond infancy or childhood. Milder cases may survive into adulthood.
How is it diagnosed?
Diagnosis is based on the recognition of key symptoms, a detailed history and a clinical examination. Isoelectric Focusing (IEF) of serum transferring is the frequently used screening test. Additional tests such as Electrospray Ionisation-Mass Spectrometry (ESI-MS) are used for confirmation. Some forms of CDG may be diagnosed through enzyme assays. Final confirmation is done by molecular testing.
Can it be treated?
Treatment is symptomatic & supportive and requires a multidisciplinary team of specialists. Supportive therapies include speech and language therapy, physiotherapy and occupational therapy. An ophthalmologist may recommend eye surgery to correct strabismus, if present. Vision loss is rare in this form of CDG. Seizures may be treated with anticonvulsants, however, may be difficult to manage. Surgery may be required to treat some skeletal malformations that cause problems. Later in life, skeletal problems may require some mobility aids and orthopaedic management. Bleeding problems do not often cause major problems, but special care and attention should be drawn to it if surgery is required; in these circumstances fresh frozen plasma is used. Organs such as liver and heart will be regularly checked. In some CDG, certain medication(s) should be avoided; ask the advice of your specialist. It is important to attend follow-up appointments and attend check-ups with various specialists.
Do my family need to be tested?
Humans have chromosomes composed of DNA. Genes are pieces of DNA that carry the genetic instruction. Each chromosome may have several thousand genes.
The word mutation means a change or error in the genetic instruction. We inherit particular chromosomes from the egg of the mother and sperm of the father. The genes on those chromosomes carry the instruction that determines characteristics, which are a combination of the parents.
This is an inherited condition. There is nothing that could have been done to prevent your baby from having this condition.
Everyone has a pair of ALG1 genes. In children with this condition, neither of these genes works correctly. These children inherit one non-working ALG1 gene from each parent.
Parents of children with ALG1-CDG are carriers of the condition. Carriers do not have the condition because the other gene of this pair is working correctly.
When both parents are carriers, in each pregnancy the risk to the baby is as follows:
- There is a 25% chance (1 in 4) of the baby having this condition.
- There is a 50% chance (1 in 2) for the baby to be a carrier of this condition.
- There is a 25% chance (1 in 4) for the baby to have two working genes and neither have this condition nor be a carrier
Genetic counselling is recommended.