Diagnosis and monitoring of mucopolysaccharidoses using disease‐specific non‐reducing end carbohydrate biomarkers

A significant need exists for improved biomarkers for differential diagnosis, prognosis and monitoring of therapeutic interventions for mucopolysaccharidoses (MPS), inherited metabolic disorders that involve lysosomal storage of glycosaminoglycans. Here, we report a simple reliable method based on the detection of abundant non‐reducing ends of the glycosaminoglycans that accumulate in cells, blood, and urine of MPS patients. In this method, glycosaminoglycans were enzymatically depolymerized releasing unique mono‐, di‐, or trisaccharides from the non‐reducing ends of the chains. The composition of the released mono and oligosaccharides depends on the nature of the lysosomal enzyme deficiency, and therefore they serve as diagnostic biomarkers. This strategy has been used to validate the cause of secondary dermatan sulfate storage in Sanfilippo disease by matching the non‐reducing end of this glycosaminoglycan with deficient iduronate‐2‐sulfatase activity. Furthermore, non‐reducing end analysis has been used to identify a novel MPS disorder. These findings underline the potential for this technology to aid in diagnosis, therapy and identification of new pathological mechanisms in lysosomal storage diseases as well as the discovery of novel MPS disorders.