Morava, Éva

AbstractCongenital disorders of glycosylation (CDG) are heterogeneous group of genetic protein and lipid glycosylation abnormalities. With some 33 reported patients, MAN1B1‐CDG belongs to the more frequent causes of CDG‐II. MAN1B1 encodes an α1,2‐mannosidase that removes the terminal mannose residue from the middle branch. Several methods have been proposed to characterize the glycosylation changes. In MAN1B1‐CDG, the abnormal accumulating N‐glycan structures are mostly absent or found in trace amounts in total human serum. To overcome this issue, in this study, we present a straightforward procedure based on the use of Endo‐β‐N‐acetylglucosaminidase H to easily diagnose MAN1B1‐CDG patients and mannosidase defects.

Congenital disorders of glycosylation (CDG) are a group of genetic disorders that affect protein and lipid glycosylation and glycosylphosphatidylinositol synthesis. More than 100 different disorders have been reported and the number is rapidly increasing. Since glycosylation is an essential post-translational process, patients present a large range of symptoms and variable phenotypes, from very mild to extremely severe. Only for few CDG, potentially curative therapies are being used, including dietary supplementation (e.g., galactose for PGM1-CDG, fucose for SLC35C1-CDG, Mn2+ for TMEM165-CDG or mannose for MPI-CDG) and organ transplantation (e.g., liver for MPI-CDG and heart for DOLK-CDG). However, for the majority of patients, only symptomatic and preventive treatments are in use. This constitutes a burden for patients, care-givers and ultimately the healthcare system. Innovative diagnostic approaches, in vitro and in vivo models and novel biomarkers have been developed that can lead to novel therapeutic avenues aiming to ameliorate the patients’ symptoms and lives. This review summarizes the advances in therapeutic approaches for CDG.

AbstractPattern recognition, using a group of characteristic, or discriminating features, is a powerful tool in metabolic diagnostic. A classic example of this approach is used in biochemical analysis of urine organic acid analysis, where the reporting depends more on the correlation of pertinent positive and negative findings, rather than on the absolute values of specific markers. Similar uses of pattern recognition in the field of biochemical genetics include the interpretation of data obtained by metabolomics, like glycomics, where a recognizable pattern or the presence of a specific glycan sub‐fraction can lead to the direct diagnosis of certain types of congenital disorders of glycosylation. Another indispensable tool is the use of clinical pattern recognition–or syndromology–relying on careful phenotyping. While genomics might uncover variants not essential in the final clinical expression of disease, and metabolomics could point to a mixture of primary but also secondary changes in biochemical pathways, phenomics describes the clinically relevant manifestations and the full expression of the disease. In the current review we apply phenomics to the field of congenital disorders of glycosylation, focusing on recognizable differentiating findings in glycosylation disorders, characteristic dysmorphic features and malformations in PMM2‐CDG, and overlapping patterns among the currently known glycosylation disorders based on their pathophysiological basis.