Urine proteome uncovers common mechanisms between mucopolysaccharidosis types I and II.

Mucopolysaccharidosis (MPS) types I and II are two types of rare lysosomal storage diseases, which lead to the accumulation of glycosaminoglycans due to the lack of the enzyme alpha-L-iduronidase and iduronate 2-sulfatase respectively. There are some similar pathogenic mechanisms and clinical phenotypes but also some specific minute manifestations between these two subtypes. We used tandem mass tag mass spectrometry to analyze the differential protein profiles in the urine of MPS I and MPS II patients, and then used parallel reaction monitoring (PRM) to verify our results. We detected the differentially expressed proteins (DEPs) of MPS I and MPS II compared with the control group separately. We focused on 227 DEPs which showed consistent changes in the urine of both MPS I and MPS II. PRM analysis verified that up-regulated hexosaminidase B and down-regulated hemoglobin alpha-1 showed significant difference in the urine of both subtypes. In addition, we found 391 DEPs by comparative analysis of MPS I and MPS II proteomes and found that DHRS2 contributed to the difference between the two subtypes by PRM verification. We found that the urine of the two subtypes showed up-regulated HEXB and down regulated HBA1, while DHRS2 was significantly different in the urine of the two subtypes.