Welcome to our CDG community! You may have just learned that one of your family members has CDG. You may be a support person for a family affected by CDG. You may be a professional taking care of a patient with CDG. CDG can be confusing for anyone. We hope this page helps you understand CDG better. Improved understanding of CDG will help you to better love and care for a person with CDG.
What is CDG?
CDG stands for Congenital Disorders of Glycosylation. CDG is a large group of rare inherited diseases affecting glycosylation.
What is Glycosylation?
Glycosylation is the process of adding sugar building blocks (also called glycans) to proteins. Even though glycans are made of many sugars this is not related to blood sugar levels or diabetes. People with CDGs have health concerns because their bodies cannot properly add sugar building blocks to proteins. Every part of the body requires glycosylation to work normally, which explains the many different health problems that affect people with CDG.
What is the history of CDG?
We have only known about CDGs since the 1980s. Each type of CDG is individually rare, so medical experience with CDG remains limited. Most physicians have not had any personal experience with CDGs.
Could my loved one have CDG?
At CDG CARE we believe that a diagnosis of CDG should be considered in every undiagnosed individual with unexplained symptoms affecting multiple body systems or single health problems that are not otherwise explained. While CDGs are rare, we believe that there are many undiagnosed and misdiagnosed patients. CDG patients are often misdiagnosed because their symptoms resemble other disorders. They may initially be diagnosed with cerebral palsy or a different genetic disorder.
There are over 400 genes in the human genome with roles in glycosylation. Only around 130 of these genes are known to cause CDG. Through the efforts of doctors, scientists, and parents, new types of CDG are discovered every year. Physicians and researchers who specialize in CDG are ready to help patients determine if they have a diagnosis of CDG. With still many CDG types to find, the true number of CDG patients remains unknown.
Having multiple unexplained health concerns should raise the possibility of CDG. Physicians should suspect CDG in children who present with the following signs and symptoms:
• hypotonia (low muscle tone)
• failure to thrive (slow growth)
• developmental delay
• hepatopathy (liver disease) presenting as elevated liver enzymes (ALT and AST)
• coagulopathy (bleeding tendencies early on and abnormal clotting as adults)
• esotropia (crossed eyes)
• cerebellar hypoplasia (changes in the brain that can be seen on brain imaging)
At a later age, adolescence or adulthood, affected individuals may have these additional clinical features:
• ataxia (poor balance and movement coordination)
• dysarthria (slurred speech)
• absent puberty in females
• retinitis pigmentosa (pigment in back of the eye)
• progressive scoliosis (curvature of the spine)
• joint contractures
How can you be sure it is CDG?
Genetic testing is the most reliable test for determining CDG. It will also determine the type of CDG. Some CDG types can be detected by a blood test for missing sugar building blocks (called a carbohydrate deficient transferrin, CDT, or transferrin IEF), but sometimes this blood test can be normal in CDG.
What should I do now that me/my child has received a confirmed diagnosis of CDG?
The first step each family should take after receiving a diagnosis of CDG is to join our CDG family support groups. The links to our current CDG Facebook groups and pages can be found on our CDG CARE homepage. Newly diagnosed families should also join CDG Connect, which is the global registry for CDG patients. CDG Connect will help CDG patients, researchers and drug developers work together to find better treatments for all CDGs. Another way to stay informed is to sign up on our Homepage for the CDG CARE semi-annual E-Newsletter which provides information and updates on our community activities as well as the latest progress in research, awareness and advocacy efforts.
If a family or clinician has specific medical questions, concerns or is in need of an urgent consultation with a CDG medical professional, we encourage you to email CDG CARE at firstname.lastname@example.org.
What can I expect in the future for my child with CDG?
Every child with CDG is special and unique. Individuals with CDG have very charming personalities and are generally happy and social. CDG symptoms vary by CDG type even among siblings and have a range of severity even in the same type of CDG that Doctors and Scientists cannot yet explain. Each CDG type can have more or less severe symptoms. Every CDG child has their own needs. Most children with CDG will need a team of specialist doctors. These are determined by their specific health concerns. The specific types of specialists may vary as health concerns change over time. They will need more frequent doctor visits than other children. Some children with CDG have serious medical problems. These can be life threatening. These may require frequent or lengthy hospital stays. Life threatening episodes typically decrease as children grow up. Some children with CDG never need a hospital visit. Others may need multiple hospital visits in the first year.
Many individuals with CDG have disabilities. These can be improved with physical, occupational, and speech therapy. These therapies are often needed lifelong.
Most CDG types do not have specific treatment or cures available. However, many of the health concerns in CDG are treatable. Current treatment for CDG patients involves screening for and treatment of health concerns. Health concerns can be decreased through preventative medicine with appropriate nutrition and scheduled immunizations.
Doctors and scientists are working to find and create more specific treatments for CDG. CDG CARE supports these research efforts. CDG CARE is actively trying to make the future even brighter for CDG patients and families.
What treatments are available for CDG?
For families: CLICK HERE to learn about how doctors will likely treat specific medical concerns.
If you are a medical professional taking care of a CDG patient and have specific medical questions, concerns, or are in need of an urgent consultation with a CDG medical professional, we encourage you to email CDG CARE at email@example.com.
Additionally, if you are in need of medical literature concerning any of the ultra-rare CDG Types that are not currently linked to this webpage, please email your request to firstname.lastname@example.org.
Why is the name of the CDG type so confusing?
There is an old name and a new name for many CDG types. CDG types were first named based on the pattern of the sugar building blocks in blood tests, type I and type II. A small letter was added chronologically for each new genetic defect identified. As the number of types of CDG increased this system became confusing. The new name is now based on the name of the affected gene followed by “-CDG”. Families who had individuals diagnosed years ago still frequently use the old name. We hope that as everyone adjusts to the new naming system it will be less confusing. We hope it will help doctors find the right information to help your child.
How many types of CDG are there?
Over 130 different genes have been determined to cause CDG. Through the efforts of doctors, scientists, and parents, new types of CDG are discovered every year. The most recently discovered CDG types may only have 1 or 2 patients currently identified. CDG types are grouped together into larger groups based on the sugar building blocks affected. Individuals in these groups have similar medical concerns. These groups include N-linked, Combined N- and O-linked, O-linked, alpha-dystroglycanopathies, GPI-anchor synthesis defects, and glycosaminoglycan disorders. Click on a link below to learn more about the different categories and types of CDGs.
N-linked CDG is the largest group and is divided into type I and type II groups. These groups are based on the pattern of abnormal sugar building blocks observed on a particular protein, transferrin.
N-linked, type I. N-linked type I CDGs typically have gene defects that affect sugar building block pathways in a portion of the cell known as the endoplasmic reticulum (ER). This is the area of the cell where new proteins are made. The transferrin pattern is the result of failure to attach entire N-linked sugar building block groups to the protein. PMM2-CDG is the most common CDG type and is a Type I CDG. Mild N-linked type I CDG patients may have isolated developmental delay. The more severe patients will have many health concerns. These health concerns can include difficulty gaining weight, low protein levels, abnormal blood coagulation, ascites, pericardial effusions, liver dysfunction, and seizures.
N-linked, type II. N-linked type II CDGs typically have gene defects that affect remodeling of sugar building blocks. This remodeling process occurs in a portion of the cell known as the Golgi apparatus. The transferrin pattern is the result of failure to remodel the N-linked sugar building block groups that were added in the ER. There is a similar range of severity associated with N-linked type II CDG as for type I CDG.
Combined N- and O-linked. Combined N- and O- linked CDGs have gene defects that affect remodeling of sugar building blocks in the Golgi apparatus. These can result in a type II CDG pattern. The genes in this group do not specifically modify N-linked sugar building blocks. Instead, they are involved in normal function of the Golgi apparatus. Defects in normal Golgi functioning also affect O-linked sugar building blocks, resulting in the combined defects. There is a wide range of severity of medical problems associated with combined N-and O- linked CDG types.
O-linked. O-linked CDG is a much smaller group of disorders than N-linked CDG. O-linked CDG frequently has a limited set of specific medical concerns isolated to one or a few body systems. O-linked CDG frequently may have no detectable abnormalities on blood tests.
Alpha dystroglycanopathies. Alpha dystroglycanopathies are a subset of O-linked CDG that affect the addition of a specific sugar building block, mannose, to a specific protein, alpha-dystroglycan. Alpha dystroglycanopathies can affect the eyes, muscles, and brain. More mild forms of alpha dystroglycanopathies may only affect the muscles, resulting in weakness that is not apparent until adulthood.
GPI-anchor synthesis defects. GPI-anchor synthesis defects affect the ability of the body to create a GPI (glycosylphosphatidylinositol) anchor. These anchors are used to attach specific proteins to cells. Many different genes can cause GPI-anchor defects. Most of these start with “PIG” named after the compound (phosphatidylinositol glycan) that becomes the GPI anchor. Most people with GPI-anchor CDG have severe seizures and some can have birth defects.
Glycosaminoglycan synthesis defects. Glycosaminoglycans (GAGs) are long structures made up of repeating patterns of two different sugars that form structures for our connective tissue. GAG synthesis defects should be suspected in patients with a combination of affected connective tissue types: bone and cartilage (shorter bones than expected, scoliosis), ligaments (joint laxity/dislocations), and sub epithelial (skin, eyes). GAG synthesis defects can be detected with genetic testing, analysis of GAGs, and specific enzyme assays.