Advancement in Clinical Glycomics and Glycoproteomics for Congenital Disorders of Glycosylation: Progress and Challenges Ahead

Congenital disorders of glycosylation (CDG) are a group of rare, multisystemic genetic diseases caused by defects in glycan biosynthesis and protein glycosylation. Their broad clinical and genetic heterogeneity often require advanced diagnostic strategies. Clinical glycomics and glycoproteomics emerge as powerful tools for understanding and diagnosing CDG by enabling high-resolution analysis of glycan structures and glycoproteins. Advancements in high-throughput mass spectrometry (MS) and site-specific glycoproteomics have led to the identification of disease-relevant biomarkers, providing insight into underlying glycosylation defects. These technologies enable detailed analysis of glycan structures and glycoproteins, improving early diagnosis, supporting biomarker discovery, and facilitating therapy monitoring. Integration with genomic and clinical data, including the use of dried blood spot testing and isotopic tracing, further enhances diagnostic precision and reveals functional consequences of pathogenic variants. While challenges remain in standardizing methods, ensuring accessibility, and implementing bioinformatics tools, global collaborations and harmonized guidelines are beginning to address these gaps. Future directions include the use of artificial intelligence in data analysis, the development of comprehensive diagnostic frameworks, and international efforts to standardize glycomic methods. Collectively, these advances reinforce the growing clinical value of glycomics and glycoproteomics in the diagnosis and management of CDG.