Congenital Glycosylation Disorder - Types, Symptoms, Diagnosis, and Management

What Is Congenital Glycosylation Disorder?

Congenital disorder of glycosylation or CDG was reported by Dr. Jaak Jaeken and team in 1980. Around 130 different types of CDG have been diagnosed to date. The CDG is a group of genetic disorders in which glycans have a metabolic defect. Glycans are single sugar-building blocks that are attached to molecules like lipids and proteins. These sugar molecules are joined chemically and are also known as polysaccharides.

Glycosylation is a process in which the glycans are altered, created, and attached to the lipids and form glycolipids. Also, when attached to protein forms glycoproteins. These two have essential functions in the body’s organs and tissues. A deficiency of any of these two enzymes leads to defects in organs.

What Are the Different Types of Congenital Glycosylation Disorder?

Congenital glycosylation disorder is categorized into four types.

1. N-Linked Protein Glycosylation Defects: Most types of CDG are classified as this type of defect that involves N-linked oligosaccharides or glycans carbohydrates. There is a deficiency in the pathway of N-glycosylation. N-linked protein glycosylation defects are further divided into two subtypes, oligosaccharide assembly and transfer (type 1) and oligosaccharide trimming and process occurring after attaching to protein (type 2).
2. O-Linked Glycosylation Defects: There is a deficiency in the pathway of O-glycosylation. Some of these defects are classified as forms of muscular dystrophy.
3. Lipid Glycosylation Defects: There is a deficiency in the two types of lipids, glycosphingolipids (GSL) and glycosylphosphatidylinositol (GPI).
4. Multiple Glycosylation Defects: Some CDG occurs due to alteration and defects in the multiple glycosylation pathways.

What Are the Different Modalities That Causes Congenital Glycosylation Disorder?

Congenital glycosylation disorder is caused due to deficiency of enzymes and proteins involved in forming glycans (sugar trees) and lipids that bind to other lipids (glycosylation). These defects occur due to genetic disorders. In most cases, CDG occurs when both parents have the CDG gene, which the child inherits. This is known as an autosomal recessive disorder. In some cases, if only one gene pair has a mutation, then that individual will not be affected by this condition but will act as a carrier, which means that person can transfer it to their child. This risk of passing CDG increases by 50 percent with each pregnancy.

What Are the Symptoms of Congenital Glycosylation Disorder?

Depending on the type and severity, the symptoms may vary in an individual. Some of the common symptoms include:

• Poor muscle tone (hypotonia).
• Seizures.
• Developmental delays.
• Nausea and vomiting.
• Diarrhea.
• Crossed eye (strabismus).
• Distinctive facial features (facial dysmorphism).
• Stroke.
• Elevated liver enzymes.
• Delayed puberty in females.
• Difficulty speaking or slurred speech.
• Difficulty in balancing or coordination disorder (ataxia).
• Poor vision at night.
• Underdevelopment of cerebellum (cerebellar hypoplasia).
• Fluid accumulation in the lungs or heart.
• Bony overgrowth or deformity.
• Scaly skin or rashes.
• Joint contractures.
• Abnormality in kidneys, heart and liver.

How Is Congenital Glycosylation Disorder Diagnosed?

Based on the symptoms, a doctor may first clinically examine the patient along with a complete medical and family history.

• Blood Test: A blood test is done to detect abnormal levels of glycans in the body. A healthcare professional will take the blood test from the arm’s vein. A fine needle is inserted into the vein, and the blood is drawn out in a vial or a test tube. The collected sample is sent to a laboratory for the investigation of the glycan levels.
• Molecular Genetic Testing: A molecular genetic test is done to detect changes in one or more genes. This genetic test is divided into different types depending on the variants of genes that need to be detected, such as targeted single gene, single gene, gene panel, and whole exome sequencing. It examines the DNA, a database that carries instructions for the body’s functions. It is always informed before genetic testing that, in some cases, the negative result does not confirm the diagnosis, and the test can be performed again. The blood test is done by a healthcare expert who takes the blood from the arm’s vein, and the sample is sent to the laboratory for further testing.

How Is Congenital Glycosylation Disorder Managed?

There is no permanent cure available for this condition, but the symptoms can be reduced and improved. Some of the treatment options include:

• Using nasogastric (NG) or G-tube to feed infants who have difficulty feeding.
• Occupational therapy helps an individual with sensory and physical problems. The occupational therapist will help the patient walk by giving certain exercises.
• Speech therapy is given to children who have difficulty speaking clearly.
• Seizures can be controlled by giving antiepileptic medications.
• For crossed eyes, corrective surgery or glasses can be advised.
• Vitamin K and Albumin helps in maintaining the liver function.

Conclusion

Congenital glycosylation disorder is a group of genetic disorders that can affect an individual's normal motor and developmental growth. There are different types of CDG defects and there is a metabolic defect of the glycans. CDG is transmitted from the parent to the child. The symptoms can vary in each person and can be easily detected by genetic testing. Though there is no permanent cure for CDG, the symptoms can be managed easily, which will help in reducing the risk of organ failure or delayed developmental growth.