The aim of this paper is to review the diagnostics of congenital disorders of glycosylation (CDG), an ever expanding group of diseases. Development delay, neurological, and other clinical abnormalities as well as various non-specific laboratory changes can lead to the first suspicion of the disease. Still common screening test for most CDG types, including CDG Ia, is isoelectric focusing/polyacrylamide gel electrophoresis (IEF). IEF demonstrates the hypoglycosylation of various glycoproteins, usually serum transferrin. Other methods, such as agarose electrophoresis, capillary electrophoresis, high-performance liquid chromatography, micro-column separation combined with turbidimetry, enzyme-(EIA) and radioimmunoassay (RIA) have also been used for screening. However, these methods do not recognize all CDG defects, so other approaches including analysis of membrane-linked markers and urine oligosaccharides should be taken. Confirmation of diagnosis and detailed CDG subtyping starts with thorough structure analysis of the affected lipid-linked oligosaccharide or protein-(peptide)-linked-glycan using metabolic labeling and various (possibly mass-spectrometry combined) techniques. Decreased enzyme activity in peripheral leukocytes/cultured fibroblasts or analysis of affected transporters and other functional proteins combined with identification of specific gene mutations confirm the diagnosis. Prenatal diagnosis, based on enzyme assay or mutation analysis, is also available. Peri-/post-mortem investigations of fatal cases are important for genetic counseling. Evaluation of various analytical approaches and proposed algorithms for investigation complete the review.

Charles University Faculty of Medicine Department of Pediatrics Hradec Kralove Czech Republic