CDG Syndrome (Congenital Disorders of Glycosylation)

Description

Congenital Disorders of Glycosylation (CDG) are a group of rare genetic disorders that affect the body‘s ability to produce or use complex sugar molecules called glycans. These glycans are essential for the proper function of many proteins and other molecules in the body. CDG can cause a wide range of symptoms, depending on the specific gene affected and the severity of the disorder. This blog will provide an overview of CDG, including its causes, signs and symptoms, diagnosis, management, and how to thrive with this condition.

Genes Involved

Over 100 genes are known to be involved in CDG, and new genes are being discovered all the time. The specific gene affected determines the type of CDG and the symptoms that develop. Some of the more common genes involved include:

PMM2: This gene is responsible for the enzyme phosphomannomutase 2, which is involved in the first step of glycosylation. Mutations in this gene cause the most common type of CDG, known as CDG type Ia.
ALG1: This gene is responsible for the enzyme alpha-1,6-mannosyltransferase, which is involved in the assembly of the glycan chains. Mutations in this gene cause CDG type Ib.
MPI: This gene is responsible for the enzyme mannose phosphate isomerase, which is involved in the conversion of mannose-6-phosphate to mannose-1-phosphate. Mutations in this gene cause CDG type Ic.
MGAT2: This gene is responsible for the enzyme N-acetylglucosaminyltransferase II, which is involved in the assembly of the glycan chains. Mutations in this gene cause CDG type II.
FUT8: This gene is responsible for the enzyme fucosyltransferase 8, which is involved in the synthesis of the Lewis X antigen. Mutations in this gene cause CDG type III.

Recognizing the Signs and Symptoms

The symptoms of CDG can vary widely depending on the specific gene affected and the severity of the disorder. Some common signs and symptoms include:

Developmental delays: This can include delays in reaching developmental milestones such as sitting, crawling, and walking.
Intellectual disability: This can range from mild to severe, depending on the specific gene affected.
Seizures: Seizures are a common symptom of CDG, and can be difficult to control.
Muscle weakness: This can lead to problems with movement and coordination.
Abnormal blood sugar levels: This can lead to hypoglycemia (low blood sugar) or hyperglycemia (high blood sugar).
Liver disease: This can cause jaundice (yellowing of the skin and eyes), abdominal pain, and swelling.
Skeletal abnormalities: This can include short stature, bone deformities, and scoliosis (curvature of the spine).
Heart defects: This can include heart murmurs, enlarged heart, and heart failure.
Immune deficiency: This can lead to increased susceptibility to infections.
Abnormal facial features: This can include a small head, flat facial features, and a broad forehead.
Vision problems: This can include nystagmus (rapid eye movements), strabismus (crossed eyes), and optic atrophy (degeneration of the optic nerve).
Hearing loss: This can occur in some individuals with CDG.

Causes

CDG is caused by mutations in genes that are involved in the process of glycosylation. Glycosylation is the process of adding sugar molecules, called glycans, to proteins and other molecules. These glycans are essential for the proper function of many proteins and other molecules in the body.

Mutations in genes involved in glycosylation can disrupt this process, leading to the production of abnormal proteins or the lack of certain important proteins. This can cause a wide range of symptoms, depending on the specific gene affected and the severity of the disorder.

Inheritance/recurrence risk

Most types of CDG are inherited in an autosomal recessive pattern, which means that both parents must carry a copy of the mutated gene for their child to inherit the disorder. If both parents are carriers, there is a 25% chance with each pregnancy that their child will inherit CDG. There is also a 50% chance that their child will be a carrier of the mutated gene.

Some types of CDG are inherited in an autosomal dominant pattern, which means that a single copy of the mutated gene is sufficient to cause the disorder. In this case, if one parent has CDG, there is a 50% chance that their child will inherit the disorder.

It is important to note that CDG can also occur due to new mutations, meaning that the mutation occurred in the child‘s egg or sperm cell and was not inherited from either parent.

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