CDG

 

What are congenital disorders of glycosylation (CDG)?

Congenital disorders of glycosylation (CDG) are a large group of rare genetic disorders that affect the addition of sugar building blocks, called glycans, to  proteins in cells throughout the body. The addition of glycans to proteins is critical to the healthy function of cells. People with CDG have a wide range of health problems because of this chemical malfunction.
While glycosylation involves sugar, as glycans are compounds of sugar molecules, CDG are not related to diabetes. Instead, CDG cause problems in the way sugar building blocks are attached to proteins within and on the surfaces of cells, affecting how cells in every part of the body function.

Causes of CDG

CDG are genetic disorders, which means that, in most cases, they are inherited from a child’s parents. In most forms of CDG, that inheritance occurs only when both parents carry the genetic mutation, generally with no symptoms themselves. (This is called an autosomal recessive pattern of inheritance.)

We inherit pairs of each of our genes, one from each parent. In autosomal recessive forms of CDG, if only one copy of a gene’s pair has the mutation, a person will not have CDG, but that person will be a carrier of the disorder. When two carriers have children together, the odds are one in four that any child they produce will have CDG. (The odds are also one in four that a particular child will not inherit the gene mutation at all, and one in two, a 50 percent risk, that the child will be a carrier.)

Forms of CDG

Several forms of CDG, such as EXT1/EXT2-CDG, are autosomal dominant conditions, which means that they can be inherited from either parent. Only one copy of the gene is needed for the condition to be expressed. If a parent has this form of CDG, the risk of passing it on is 50 percent for each child produced, regardless of the sex of the parent or child.

In some cases, the gene mutations that cause CDG are not inherited from the parents. They are simply random mutations and are new in the people who develop the disorders.

Over 400 genes play roles in the healthy expression of glycosylation, and mutations in any of roughly 130 of these have been found to cause different forms of CDG. Because the study of CDG is relatively new, more genes may yet be found to be involved. The first forms of CDG were identified in the 1980s, and knowledge of the conditions continues to expand as new patients are identified and additional research is done.

Signs and symptoms of CDG

CDG affects cell function in many parts of the body, so a combination of unexplained health problems can be an indication of the disorder. Symptoms of CDG in infancy and childhood may include:

• low muscle tone or floppiness (hypotonia)
• poor growth, failure to thrive
• developmental delays
• liver disease (hepatopathy) with elevated liver enzymes
• abnormal bleeding or blood clotting
• misaligned or crossed eyes (strabismus)
• seizures
• stroke-like episodes
• heart problems, including fluid accumulation around the heart or lungs (pericardial or pleural effusion) or thickening and stiffening of the heart muscle (cardiomyopathy)

As children enter adolescence and grow to adulthood, additional symptoms may include:

• balance and coordination problems (ataxia)
• slurred speech (dysarthria)
• no puberty in girls
• progressive curvature of the spine (neuromuscular scoliosis)
• joint contractures
• poor night vision and loss of peripheral vision (signs of retinitis pigmento