Sialic acid-Retaled disorders: Advances in pathophysiology, diagnostic challenges, and differentiating mimics

Sialic acid-related disorders (SARD) represent a heterogeneous and challenging group of lysosomal storage diseases arising from defects in sialic acid metabolism and transport. Their clinical spectra range from mild developmental delays and subtle dysmorphisms to severe neurodegeneration and early childhood mortality. Substantial overlap with other metabolic and neurological conditions complicates early and accurate diagnosis. This review synthesizes current knowledge on sialic acid biology and delineates the key enzymatic and genetic defects underlying these disorders devised in free and bound sialic acid storage diseases. Emphasis is placed on integrative diagnostic strategies, including biochemical assays, genetic testing, and advanced imaging techniques, which enable more precise differentiation from phenotypically similar conditions. Finally, we highlight emerging therapeutic approaches, ranging from supportive care to experimental gene and enzyme replacement therapies, and we propose a structured diagnostic algorithm. By refining our understanding of SARD pathophysiology and enhancing diagnostic accuracy, we set the stage for earlier intervention, improved patient outcomes, and the advancement of targeted therapeutic modalities.