Congenital disorders of Glycosylation

Background

Congenital disorders of glycosylation (CDG) are a group of inherited metabolic conditions that affect all parts of the body. In CDG, there are abnormal sugar chains attached to proteins, called glycoproteins, which disrupts their proper function. This can affect any organ system and cellular function. There is a wide range of CDGs –  over 40 different types have been recognised. Some of them are very rare. They are named by the abbreviation of the enzyme being deficient, followed by CDG. The most often diagnosed type is PMM-CDG, formerly known as CDG-Ia.

Credits

Medical text written June 2002 by Dr A Morris, Consultant Paediatrician with special interest in metabolic disease, Willink Biochemical Genetics Unit, Royal Manchester Children’s Hospital, Manchester, UK. Last updated February 2013 by Dr S Grünewald, Consultant in Metabolic Medicine, Great Ormond Street Hospital, London, UK.

Although great care has been taken in the compilation and preparation of all entries to ensure accuracy, we cannot accept responsibility for any errors or omissions. Any medical information is provided is for education/information purposes and is not designed to replace medical advice by a qualified medical professional.

This entry is pending review, and certain details may no longer be up to date. Please ring our helpline or email our Rare Conditions Information Officer for more information.

What are the symptoms?

PMM-CDG
People affected may have:

  • neurological problems such as developmental delay (see entry Global Developmental Delay)
  • visual problems such as squint or retinitis pigmentosa
  • cerebellar hypoplasia (underdevelopment of the cerebellum in the brain)
  • liver disease
  • kidney cysts
  • heart abnormalities
  • diarrhoea
  • abnormal fat distribution under the skin
  • patients often have inverted nipples.

A similar range of problems are seen in most other forms of CDG. An exception is PMI-CDG, previously called CDG-Ib.

PMI-CDG
People affected may have liver disease, diarrhoea and severe failure to thrive. They may have low blood sugar levels due to too much insulin, but they do not have neurological problems.

What are the causes?

In all forms of CDG, there is a problem making glycoproteins. Glycoproteins have several important functions, including signalling how cells in the body interact with one another, assisting the transfer of nutrients around the body, having a role in the coagulation of blood and acting as hormones in regulating certain activities or organs in the body. A number of enzymes are involved in attaching sugars to glycoproteins. In each type of CDG, a different one of these enzymes is faulty, due to a genetic change (mutation).

How is it diagnosed?

Most forms of CDG can be screened for by electrophoresis of transferrin, a glycoprotein present in blood. Electrophoresis is a method that sorts molecules according to their size and charge – by doing this, scientists can see if there is any change to the sugar chain, which indicates CDG. Those results are then followed up by enzyme and/or genetic testing to identify the distinct CDG subtype.

How is it treated?

Although there is no cure for the different CDG types, lots can be offered to the patient.

PMM-CDG
Treatment aims to provide relief for any symptoms and support in the care of the individual. Feeding might be helped with a tube. A wide range of specialists may need to be consulted; these may include paediatricians, neurologists, ophthalmologists, orthopaedic specialists (skeletal), physiotherapist, speech therapists and the aid of a dietician may also be useful.

PMI-CDG
This is the only CDG that has an effective treatment. Individuals are given a specific sugar called mannose, which then can improve the glycosylation. This treatment has been successful in several cases of PMI-CDG.

The support group CLIMB have information on file for the rarer types of CDG. Please contact them for more information.

Inheritance patterns and prenatal diagnosis

Inheritance patterns
All forms of CDG show an autosomal recessive pattern of inheritance. Affected families should be referred to a genetics centre for information and support.

Prenatal diagnosis
This can be offered if the genetic background (mutation) in a family is already known.

Is there support?

Information and support in the UK for congenital disorders of glycosylation is provided by Climb (see entry Inherited Metabolic diseases).

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