Molecular characteristics:
MAN1B1 deficiency is inherited autosomal recessively. That is; consanguineous marriages will increase the likelihood of disease occurrence. Homozygous or compound heterozygous pathogenic variations will lead to clinical findings. Over 40 patients of MAN1B1-CDG have been described up-to-date.
This gene encodes an enzyme called α-1,2-mannosidase localized primarily in the organelles called Golgi apparatus, and the endoplasmic reticulum. This enzyme plays a pivotal role in N-glycosylation by taking a part in the maturation of glycans, as well as disposal of misfolded glycoproteins.
Pathophysiological mechanism:
Proteins need specific parts and decorations (glycans) to work properly. The MAN1B1 removes tiny parts from the decorations (N-glycans) on certain proteins. When the MAN1B1 gene doesn't work right, the whole protein can't function properly. This also damages the organelle where the proteins get decorated (Golgi apparatus). Things get disorganized, causing mistakes and misfolded decorations. These mistakes sometimes trigger a "cleanup crew" (ER-associated protein degradation): They throw away the messed-up proteins to protect the body.
Diagnostic testing:
CDG-II are commonly detected using special tools called isoelectric focusing or capillary electrophoresis or HPLC analysis of transferrin showing decreased level of tetrasialo glycoform and increased tri-, di-, mono- and a-sialo transferrin glycoforms. Definitive diagnosis requires analysis of the MAN1B1 gene, where several methods are available, according to the clinical symptoms and laboratory findings.
MAN1B1