ALG12-congenital disorder of glycosylation (ALG12-CDG) – ALG12 gene.
ALG12-congenital disorder of glycosylation (ALG12-CDG), also known as congenital disorder of glycosylation type Ig, is an inherited process with various signs and symptoms that can affect various body systems.
Usually, the first signs and symptoms related to this process are manifested in childhood, and may include difficulties in feeding, as well as in growing and gaining weight at the expected speed, in addition to intellectual disability, late development, hypotonia, and in some cases seizures. In addition, some people have physical abnormalities, such as microcephaly and unusual facial features that may include epicantic folds, a prominent nasal bridge and abnormally shaped ears; abnormal genitals in men, such as micropenis and undescended testicles. Other signs related to this process may include abnormally low concentrations of immunoglobulin G (IgG) and, less frequently, cardiac and skeletal muscle abnormalities.
This process is due to mutations in the ALG12 (ALG12, alpha-1,6-mannosyltransferase) gene, located on the long arm of chromosome 22 (22q13.33), which encodes an enzyme that participates in glycosylation. During this process, complex chains of oligosaccharides bind to proteins and lipids. Glycosylation modifies proteins so that they can fully perform their functions. The oligosaccharides are formed by many sugar molecules that bind to each other in a gradual process, forming a complex chain. The enzyme encoded from the ALG12 gene transfers mannose to the growing oligosaccharides at a particular step in chain formation. Once the correct number of sugar molecules bind, the oligosaccharide binds to a protein or lipid.
At least 13 mutations in the ALG12 gene related to the development of congenital disorder of ALG12 glycosylation have been identified. The identified mutations result in the synthesis of an abnormal enzyme with little activity. Without an enzyme that works properly, mannose cannot be added to the chain efficiently, so the resulting oligosaccharides are generally of incomplete length. Although these oligosaccharides can be transferred to proteins and lipids, the process is not as efficient as with the full length oligosaccharide. As a consequence, glycosylation is reduced.
This disease is inherited with an autosomal recessive pattern, which means that both copies of the gene in each cell must have mutations for the alteration to be expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually do not show signs and symptoms of the disease.
Tests performed in IVAMI: in IVAMI we perform the detection of mutations associated with the congenital disorder of ALG12 glycosylation (ALG12-CDG), by means of the complete PCR amplification of the exons of the ALG12 gene, and their subsequent sequencing.
Recommended samples: non-coagulated blood obtained with EDTA for separation of blood leucocytes, or a card with a dried blood sample (IVAMI can mail the card to deposit the blood sample).