The Critical Role of Fractionated Urine Glycosaminoglycans in the Evaluation of Mucopolysaccharidosis Type II in Four Unrelated Families

Since 2015, Ann and Robert H. Lurie Children's Hospital has performed diagnostic testing for infants who screen positive for mucopolysaccharidosis type II (MPS II) on the Illinois newborn screen. Preliminary diagnostic testing includes measurement of plasma iduronate-2-sulfatase enzyme activity and urinary glycosaminoglycan analysis, followed by sequencing of the IDS gene. These diagnostic studies rule out or confirm a diagnosis of MPS II for most cases. However, occasionally, a diagnosis of MPS II remains uncertain following initial diagnostic studies. In this case series, we describe our experience with uncertain diagnoses of MPS II, outline our approach to confirming a diagnosis of MPS II, and emphasize the diagnostic utility of fractionated urine glycosaminoglycans analysis.