Congenital disorder of glycosylation type 1G

Synonyms

1

Overview

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 beenidentified 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 1G:

Type IG is caused by a defect on chromosome 22q13.33 and involves the gene for a particular enzyme (dolichyl-P-mannose:Man-7-GlcNAc-2-PP-dolichyl-alpha-6-mannosyltransferase). It is an inherited disorder with varying signs and symptoms that can affect several body systems. Individuals with ALG12-CDG typically develop signs and symptoms of the condition during infancy. They may have problems feeding and difficulty growing and gaining weight at the expected rate (failure to thrive). In addition, affected individuals often have intellectual disability, delayed development, and weak muscle tone (hypotonia), and some develop seizures.

Some people with ALG12-CDG have physical abnormalities such as a small head size (microcephaly) and unusual facial features. These features can include folds of skin that cover the inner corners of the eyes (epicanthal folds), a prominent nasal bridge, and abnormally shaped ears. Some males with ALG12-CDG have abnormal genitalia, such as a small penis (micropenis) and undescended testes.
People with ALG12-CDG often produce abnormally low levels of proteins called antibodies (or immunoglobulins), particularly immunoglobulin G (IgG). Antibodies help protect the body against infection by attaching to specific foreign particles and germs, marking them for destruction. A reduction in antibodies can make it difficult for affected individuals to fight infections.

Less common abnormalities seen in people with ALG12-CDG include a weakened heart muscle (cardiomyopathy) and poor bone development, which can lead to skeletal abnormalities.

Symptoms

  • Weak suck
  • Unusual fat deposits
  • Failure to thrive
  • Reduced muscle tone (hypotonia)
  • Psychomotor retardation
  • Small head size (microcephaly)
  • Unusual facial appearance
  • Recurring ear, nose, throat and respiratory infections
  • Reduced IgG levels
  • Delayed motor development
  • Delayed mental development
  • Seizures
  • Prolonged partial thromboplastin time
  • Underdeveloped genitals
  • Immunodeficiency
  • Blindness
  • Deafness
  • Cardiomyopathy
  • Childhood death
  • Abnormal skeletal ossification
  • Feeding difficulties
  • Impaired immunity

Treatment

No treatment is available for most of these disorders.