High-Risk Population Screening By Differential Diagnosis For Mucopolysaccharidoses (mpss)

Mucopolysaccharidoses (MPSs) are a group of chronic, progressive lysosomal storage diseases (LSDs) with multi-system impairments. These disorders are caused by an enzyme deficiency resulting in the inability to break down glycosaminoglycans (GAGs; formerly called mucopolysaccharides) and their accumulation in tissue. Depending on which of the eleven known enzymes are affected as well as the level of enzyme activity, different clinical manifestations are described varying from mild to severe forms with potentially early death. Differential diagnosis by phenotype is very challenging or sometimes not possible. To overcome limitations, our medical laboratory has developed, validated, and accredited a novel diagnostic panel for differential diagnosis of MPSs utilizing single Dried Blood Spot (DBS). Our assay includes testing for MPS I (α-L-Iduronidase), MPS II (Iduronate-2-sulfatase), MPS IIIB (N-α-Acetylglucosaminidase), MPS IVA (N-Acetylgalactosamine-6-sulfate-sulfatase), MPS VI (Arylsulfatase B), MPS VII (ß-Glucuronidase). Here we are presenting data from high-risk population screening of over 8,000 samples from over 57 countries. In total, over 1,000 MPSs positive patients were confirmed within the tested cohort and a retrospective data analysis was performed based on origin and type of MPS. The highest incidences were observed for MPS I, MPS VI, and MPS IVA with significant differences linked to the sample origin. In general, for Europe and Africa, similar distributions of the investigated MPSs were observed, compared to the Middle East with a divergent distribution of MPS I, MPS IVA, and MPS VI. The presented data underlines the benefit of a fast and reliable diagnostic workflow for MPS-suspected individuals.