Clinical glycomics comprises a spectrum of different analytical methodologies to analyze
glycan structures, which provides insights into the mechanisms of glycosylation. Within clinical diagnostics, glycomics serves as a functional readout of genetic variants, and can form a basis for
therapy development, as was described for PGM1-CDG. Integration of glycomics with genomics has resulted in the elucidation of previously unknown disorders of glycosylation, namely CCDC115-CDG, TMEM199-CDG, ATP6AP1-CDG, MAN1B1-CDG, and PGM1-CDG. This review provides an introduction into protein glycosylation and presents the different glycomics methodologies ranging from gel electrophoresis to mass spectrometry (MS) and from free
glycans to intact
glycoproteins. The role of glycomics in the diagnosis of
congenital disorders of glycosylation (CDG) is presented, including a diagnostic flow chart and an overview of glycomics data of known CDG subtypes. The review ends with some future perspectives, showing upcoming technologies as system wide mapping of the N- and O-glycoproteome, intact
glycoprotein profiling and analysis of
sugar metabolism. These new advances will provide additional insights and opportunities to develop personalized
therapy. This is especially true for
inborn errors of metabolism, which are amenable to causal
therapy, because interventions through supplementation
therapy can directly target the pathogenesis at the molecular level.