Congenital Disorders of Glycosylation: Symptoms, Treatment, Prognosis, Diagnosis

What is Congenital Disorders of Glycosylation?

Congenital disorders of glycosylation are shorty known as CDG. It is a collection of inherited metabolic disorders. These disorders affect a process called as glycosylation. Glycosylation is a very complex process by which cells in the human body build’s long chains of sugar and this chain is attached to proteins commonly known as glycoproteins. Various steps are involved in this process; every step is initiated by a different type of protein which is called an enzyme. Individuals who suffer from congenital disorders of glycosylation are likely to be missing a protein or enzymes which are required for glycosylation. There are various types of congenital disorders of Glycosylation. The type of congenital disorders of glycosylation is decided by the enzyme missing in the body that is required for the process of glycosylation. Till now there 19 different types of Congenital Disorders of Glycosylation identified. Among all the known Congenital Disorders of Glycosylation, the most common form is Congenital Disorders of Glycosylation type IA[1]. The symptoms vary from person to person. Congenital disorders of Glycosylation can affect any part of the body. It is known to exists from infancy due to the fact that it is an autosomal recessive condition. The deficiency of the enzyme will affect the neurological component of the person which will lead to a delay in the growth.

Symptoms of Congenital Disorders of Glycosylation

Congenital disorders of glycosylation are caused by a deficiency of protein and are divided into two groups namely N-glycosylation and O-glycosylation. There are various symptoms of congenital disorders of glycosylation that a person may suffer from and it varies from person to person. Some people may develop severe symptoms with multiple problems while other people may have minor symptoms of congenital disorders of glycosylation. Some of the symptoms experienced by people suffering from Congenital Disorders of Glycosylation are:

  • Severe developmental delay.
  • Problems related to multiple organs may exist.
  • Diarrhea
  • Hypoglycemia
  • Liver problems and excessive protein loss
  • Abnormal circulation of concentrated carbohydrate
  • Fat tissues below the skin
  • Abnormal blood clotting
  • Physiological abnormalities
  • Abnormalities in retinal pigmentation. Other types of eye abnormalities are also seen in some cases with distinctive facial features.
  • Deposition of fluid around the heart and lungs.

Diagnosis of Congenital Disorders of Glycosylation

When congenital disorder of Glycosylation is medically detected or diagnosed, the very first step is to arrange the testing of the congenital disorder of Glycosylation through the biochemical process in the serum or plasma inclusive of the CDT and N-glycan examination[2]. The testing of the CDT and N-glycan testing in the serum can only diagnose the N-glycosylation shortcoming[1]. Hence this procedure would be inadequate to diagnose the distinguishing of the isolated O-glycosylation or the GPI anchor flaws. The globulin of the isoform analysis was actually acquired by isoelectric concentration of globulin as the failure of N-glycan combination leads to insufficiency of the sialic acid which causes a change in the serum globulin and hence it’s cathodal relocation on an electrophoretic field. Nevertheless, the analysis on the basis of the mass spectrograph of the globulin and N-glycan have now took the place of isoelectric concentration by recognizing particular alterations in the oligosaccharides by mass and charge.

Prognosis of Congenital Disorders of Glycosylation

There are various types of congenital disorders of glycosylation known till now. Due to the fact that Congenital Disorders of Glycosylation is caused by a deficiency of different enzymes in the body, the prognosis is difficult to predict; in some cases, it cannot be predicted at all.

Treatment for Congenital Disorders of Glycosylation

The treatment in most cases of the congenital disorder of glycosylation types is extensively supportive, with very little exceptions being present. The oral mannose is transformed into the mannose-6-phosphate by the process of hexokinases in the fluid present in the cell membranes leading to the bypassing of the block of enzymes and giving rise to the lacking of substrate. Mannose additions generally start on the per day basis at 1g per kg depending on the body weight of that person which is further divided into 4 to 6 doses each day. While enteropathy, which is considered to be life threatening protein wasting is quite reactive in the case of mannose therapy, the disease caused in the liver which is referred to the MPI congenital disorder of glycosylation, may continue to rise. The medical signs improve at a fast rate and the globulin take months to recover although the liver disease may improve on a continuous scale of development when treatment is continued.

There should be the presence of caution when adding mannose to a patient during her pregnancy period as the mannose regulation in the pregnant hypomorphic phoshomannose isomerise mouse representations can lead to the consequence of embryonic lethality and blindness in the pups. Additionally, the mannose pushed through the veins has been related with lessening of consciousness and seizures which can be resolved through the regulation of glucose in the body. The therapy of the PMM2 congenital disorder of glycosylation is extensively helpful and is developed on the basis of symptomatology. Nevertheless, the forthcoming medical trails on mannose-1 phosphate substrate exchanging treatment are recently under progress.

For the other types of congenital disorder of glycosylation, the different oral simple sugars have been observed with the goal of theoretically progress hypoglycosylation. There has been made attempts to try for SLC35C1 congenital disorder of glycosylation and galactose for PGM1 congenital disorder of glycosylation and SLC35A2 congenital disorder of glycosylation with variegated consequences[1]. D-galactose at 1.0 – 2.5 g per kg each day has been manifested as a required amount to improve the condition of hypoglycaemia, endocrinopathy and coagulopathy in PGM1 congenital disorder of glycosylation. Galactose has also been studied to make improvement in the condition of endocrinopathy and coagulopathy in TMEM165 congenital disorder of glycosylation and SLC39A8 congenital disorder of glycosylation. Substantial clinical development was also described in SLC39A8 congenital disorder of glycosylation patients on a dosage of 15-20 mg per kg on a per day basis of MnSO4. Clinical tests are continuously on to observe the utilisation of N-acetylmannosamine in GNE congenital disorder of glycosylation and various tests that are performed before the actual trial are ongoing for the other Congenital disorder of Glycosylation.


Apart from the medical research steps, considerable mortality is present for the children suffering from congenital disorder of Glycosylation within one year of their life due to failure of multiple organs or chronic infection. Kids with congenital disorder of Glycosylation may have the presence of sudden onset of the intractable seizures, multi-organ disease or chronic hypoalbuminemia developing into anasarca. Some of the patients react to the aggressive dieresis and albumin exchange while others are deflated to the therapy.

The advancement of the genome-editing methodology and better comprehension of the procedure of the illness surrounded by the diagnostic guidance of congenital disorder of Glycosylation makes the subsequent development in the field of targeted therapy to be reassuring.


  1. Chang, I., He, M., & Lam, C. Congenital disorders of glycosylation. Annals Of Translational Medicine, (2018). 477-477.