General Introduction about Congenital disorder of glycosylation:
Congenital disorder of glycosylation (carbohydrate-deficient glycoprotein syndrome) is one of several rare inborn errors of metabolism in which glycosylation of a variety of tissue proteins and/or lipids is deficient or defective. Congenital disorders of glycosylation are sometimes known as CDG syndromes. They often cause serious, sometimes fatal, malfunction of several different organ systems (especially the nervous system, muscles, and intestines) in affected infants.
Congenital disorders of glycosylation (CDG) is an umbrella term for 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 sugar 'trees' (glycans) are created, altered and chemically attached to certain proteins or fats (lipids). 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 lead to a variety of symptoms potentially affecting multiple organ systems. CDG can affect any part of the body, and there is nearly always an important neurological component. CDG can be associated with a broad variety of symptoms and can vary in severity from mild cases to severe, disabling or life-threatening cases. CDG are usually apparent from infancy. Individual CDG are caused by a mutation to a specific gene. Most CDG are inherited as autosomal recessive conditions.
CDG was 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. Recently, Jaeken and colleagues have proposed a classification system that names each subtype by the official abbreviation of its defective gene followed by a dash and CDG. For example, congenital disorder of glycosylation type 1a is now known as PMM2-CDG. PMM2 is the defective gene that causes this subtype of CDG.
CDGs are classified as Types I and II (CDG-I and CDG-II), depending on the nature and location of the biochemical defect in the metabolic pathway relative to the action of oligosaccharyltransferase. The most commonly used screening method for CDG, analysis of transferrin glycosylation status by isoelectric focusing, ESI-MS, or other techniques, distinguish between these subtypes, which are called Type I and Type II patterns. Currently, twenty-two CDG Type-I and fourteen Type-II subtypes of CDG have been described.
Congenital disorder of glycosylation type 1C:
A very rare inherited metabolic disorder where defective carbohydrate compounds are attached to glycoproteins and thus impairing glycoprotein function. Approximately 54 individuals have been diagnosed with ALG6-CDG.
- Deficits in attaining developmental milestones
- Inability to control voluntary movements (ataxia)
- Stroke-like episodes that involve an extreme lack of energy (lethargy) and temporary paralysis
- Blood clotting disorders
- Eye abnormalities including eyes that do not look in the same direction (strabismus) and degeneration of the retina
- Eye disorder called retinitis pigmentosa, which causes vision loss.
- Psychomotor retardation
- Small head
- Feeding difficulties
- Finger abnormalities
- Deep vein thrombosis
- Pseudotumor cerebri
- Endocrine disturbances
- Hypergonadotropic hypogonadism, which affects the production of hormones that direct sexual development. As a result, most females with ALG6-CDG do not go through puberty
No treatment is available for most of these disorders.