Clinical utility of untargeted urine oligosaccharide screening

High-resolution urine oligosaccharide screening with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been clinically available for 10 years and has been used to help diagnose a wide spectrum of disorders. The untargeted nature of MALDI-TOF MS analysis gives it broad clinical utility. Here we report characteristic profiles for several disorders that had not previously been described using this method, including lysosomal disorders, congenital disorders of glycosylation, and glycogen storage disorders. In addition, we review the clinical performance of the assay in our laboratory and provide basic test performance information for each condition. A total of 4445 analyses performed with 4145 unique patient samples generated 139 confirmed and presumptive positive results and 16 false-positive results. The disorder with the highest rate of false positivity was Pompe disease, which has an oligosaccharide profile similar to that seen in formula-fed infants. The positive predictive value of urine oligosaccharide screening with MALDI-TOF MS was 89.7 % across all conditions. For 10 of the 16 conditions detected during the study period, no false-positive results occurred. No known false-negative results were reported for any of the targeted conditions. Urine oligosaccharide analysis with MALDI-TOF MS, which uses an accessible specimen type and offers quick turnaround time, is an effective initial screening method for patients with a clinical presentation suggestive of a lysosomal disorder.