Mucopolysaccharides

The mucopolysaccharidoses (MPS) are a set of inherited metabolic disorders arising due to defects in specific enzymes responsible for the lysosomal degradation of complex sugars known as glycosaminoglycans (GAG). Composed of repeating disaccharide units, GAG can be sub-classified into five broad classes based on their composition, chondroitin sulphate, dermatan sulphate, heparan sulphate, hyaluronan and keratan sulphate, and incomplete degradation of one or more is the hallmark of each MPS. Following clinical indicators such as coarse facial features, joint and skeletal deformities, cardiac and respiratory insufficiency and/or intellectual impairment, the laboratory diagnosis of MPS typically begins with the measurement of GAG in urine, methodology that has evolved considerably from simple dye-binding assays to more complex analysis of the fine structure of GAG, the latter able to inform on the MPS subtype. Traditionally considered a second-tier test in the diagnostic algorithm, enzymatic determinations are now possible in dried filter paper blood spots using a multiplex format enabling multiple MPS to be tested simultaneously. Following urine GAG measurements and/or enzymatic determinations in blood/cells, the final step in the diagnostic pipeline is the identification of pathogenic variants in the requisite gene. This also enables cascade testing for families.