Glycosylation, SLC35A2-congenital disorder of glycosylation (before type IIm) - SLC35A2 gene

The congenital alteration of glycosylation related to SLC35A2 (SLC35A2-CDG), formerly known as congenital disorder of glycosylation type IIm, is an inherited condition that causes neurological problems and other abnormalities.

The signs and symptoms of this process and its severity vary among the people affected and may include seizures accompanied by muscle rigidity, encephalopathy, unusual facial features, skeletal abnormalities and hypotonia. In addition, affected individuals have severe intellectual disability and developmental delay, lack of growth and weight gain, and in some cases, vision or hearing problems.

This process is due to mutations in the SLC35A2 (solute carrier family 35 member A2) gene, located on the short arm of chromosome X (Xp11.23), which encodes an enzyme that is involved in glycosylation. Specifically, the enzyme encoded from this gene transfers galactose to the growing oligosaccharides at a particular step in the formation of the sugar chain. Once the correct number of sugar molecules come together, the oligosaccharide binds to a protein or lipid.

At least nine mutations in the SLC35A2 gene have been identified in individuals with congenital alteration of the glycosylation related to SLC35A2. Mutations of the SLC35A2 gene result in the synthesis of an abnormal enzyme with reduced or no activity. Without a properly functioning enzyme, glycosylation cannot be carried out normally and the oligosaccharides are incomplete. The signs and symptoms of SLC35A2-CDG are likely due to altered glycosylation of proteins and fats that are needed for the normal function of various organs and tissues. Over time, in some individuals glycosylation becomes normal. Although the cause of this correction is unknown, the restoration of glycosylation in these people does not seem to improve the signs and symptoms of the disease.

The congenital alteration of the glycosylation related to SLC35A2 is inherited with a dominant pattern linked to X. In women, a mutation in one of the two copies of the gene in each cell is sufficient to express the process. In males, it is believed that a mutation in the single copy of the gene in each cell is incompatible with life. Some men with SLC35A2-CDG have a mutation in only some of the body's cells, a situation known as mosaicism. A feature of X-linked inheritance is that parents cannot pass traits linked to X to their children.

At the beginning of embryonic development in women, one of the two X chromosomes is permanently inactivated in somatic cells. Deactivating X ensures that women, like men, have only one active copy of the X chromosome in each cell of the body. In general, the inactivation of X occurs at random, so that each X chromosome is active in about half of the body's cells. Sometimes inactivation of X is not random, but biased, and an X chromosome is active in more than half of the cells. The biased inactivation of X allows the normal copy of the gene to be expressed and results in the synthesis of the normal enzyme in most of the cells in the affected women. However, it is thought that the inactivation of X in the nerve cells of the brain may not be biased and, therefore, the mutated SLC35A2 gene is expressed in these cells.

Tests performed in IVAMI: in IVAMI we perform the detection of mutations associated with the congenital disorder of the glycosylation related to SLC35A2, by means of the complete PCR amplification of the exons of the SLC35A2 gene, and their subsequent sequencing.

Recommended samples: blood drawn with EDTA for separation of blood leukocytes, or card impregnated with dried blood sample (IVAMI can mail the card to deposit the blood sample).