User:Abhishek Nayak/sandbox

INTRODUCTION
"Congenital disorder of glycosylation is a rapidly expanding group of rare genetic, metabolic disorders due to defects in complex chemical process known as glycosylation. Glycosylation is the process by which glycans are created, altered and chemically attached to certain proteins or fats. When these sugar molecules are attached to proteins, they form glycoproteins; when they are attached to lipids, they form glycolipids. Glycoproteins and glycolipids have numerous important functions in all tissues and organs. Glycosylation involves many different genes, encoding many different proteins such as enzymes. A deficiency or lack of one of these enzymes can cause serious, sometimes fatal, malfunction of several different organ systems (especially the nervous system, muscles, and intestines) in affected infants.Most CDG are inherited as autosomal recessive conditions. Introduction CDG were first reported in the medical literature in 1980 by Dr. Jaak Jaeken and colleagues. More than 80 different forms of CDG have been identified in the ensuing years. Several different names have been used to describe these disorders including carbohydrate-deficient glycoprotein syndromes."

DISORDERS OF PROTEIN N-GLYCOSYLATION
A biologically very important group of carbohydrates is the asparagine (Asn)-linked, or N-linked, oligosaccharides. These oligosaccharides are created in a specific order to create specific sugar trees, which are then attached to proteins on various cells. Disorders of N-glycosylation are due to an enzyme deficiency or other malfunction somewhere along the N-glycosylation pathway. As long as the defect is not identified, disorders of N-glycosylation are subdivided into defects of oligosaccharide assembly and transfer and defects in oligosaccharide trimming and processing that occur after they are bound to proteins.

Some of the disorders of N-glycosylation include:

 * PMM2-CDG – This disorder is the most common type of CDG. More than 700 individuals have been identified. The disorder can be broken down into three stages: infantile multisystem, late-infantile and childhood ataxia-intellectual disability stage, and an adult stable stage. PMM2-CDG can be associated with a wide variety of symptoms and varying severity. This disorder was formerly known as CDG-Ia.


 * MPI-CDG – This form of CDG is distinct from other forms because neurological symptoms are usually absent. The disorder is characterized by profoundly low levels of blood sugar (hypoglycemia), scarring (fibrosis) of the liver, failure to thrive, and cyclic vomiting. Some individuals may develop recurrent blood clots (thromboses), gastrointestinal bleeding, and protein-losing enteropathy. Additional symptoms can include vomiting, diarrhea, abdominal pain, and an enlarged liver. The specific symptoms vary greatly even among members of the same family. Approximately 25 individuals have been diagnosed with MPI-CDG. This disorder was formerly known as CDG-Ib. It is the only CDG with an efficient treatment (oral mannose). Without this treatment affected individuals usually die from liver failure.

Some of the disorders of protein O-Glycosylation
Some of these disorders are better known than the N-linked forms and many have more traditional names. In some cases, they have also been classified as subtypes of other umbrella groups (e.g: muscular dystrophy). In general, disorders of O-linked glycosylation show more dysmorphic features. These disorders include:


 * EXT1/EXT2-CDG – These subtypes of CDG (also named hereditary multiple exostoses) are characterized by multiple bony growths or tumors (exostoses) on the growing end of the long bones of the legs, arms and fingers and toes. These bony growths are covered by cartilage and usually continue to grow until puberty. Exostoses can lead to bone deformities, skeletal abnormalities, nerve compression, reduced range of motion of joints, and short stature. Malignancy occurs in about 5 %. They are caused by mutations of the EXT1 and EXT2 genes.


 * B4GALT7-CDG – This subtype of CDG has been reported in 27 patients. Affected individual can develop a prematurely aged appearance, fine curly hair, [sparse eyebrows], loose but elastic (hyperelastic) skin, abnormally loose or mobile joints (joint hyperlaxity), microcephaly and features of Ehlers-Danlos syndrome. This disorder is also known as the progeroid form of Ehlers-Danlos syndrome.

CAUSES
Most forms of CDG are inherited as autosomal recessive conditions. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25 percent with each pregnancy. The risk to have a child who is a carrier like the parents is 50 percent with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25 percent. The risk is the same for males and females. A simple blood test to analyze the glycosylation status of transferrin can diagnose CDG due to N-glycosylation. Transferrin is a glycoprotein found in the blood plasma and that is essential for the proper transport of iron within the body. Abnormal transferrin patterns can be detected through a test known as isoelectric focusing (IEF). IEF allows physicians to separate molecules such as proteins or enzymes based upon their electrical charge. This allows physicians to detect abnormal serum transferrin. IEF is the standard test for diagnosing CDG due to a defect of N-glycosylation. Another test known as electrospray ionization-mass spectrometry may be used to detect abnormal transferrin.

CLINICAL TESTING
Once a defect of N-linked glycosylation is diagnosed, further testing is required to determine the specific subtype. Some subtypes of CDG can be diagnosed through an enzyme assay, a test that measures the activity of a specific type of enzyme. However, for many subtypes no enzyme assay has been developed.

TREATMENT
Individuals with MPI-CDG are treated with oral mannose. Some individuals with SLC35C1-CDG (CDG-IIc) have been treated with fucose. Some individuals with PIGM-CDG have been treated with butyrate,

Molecular genetic testing is needed to confirm a diagnosis of CDG.