Urinary glycosaminoglycan excretion quantified by an automated semimicro method in specimens conveniently transported from around the globe

Chester B Whitley, Richard C. Spielmann, Gerrard Herro, Suzanne Severson Teragawa

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33 Scopus citations


Current and future treatments for children with mucopolysaccharidosis (MPS) diseases require early, presymptomatic diagnosis, yet existing diagnostic methods to quantitate urinary glycosaminoglycan (GAG) are labor-intensive, and thus not applicable for newborn screening. Direct and rapid quantification of GAG excretion with 1,9-dimethylmethylene blue (DMB) is applicable to small volumes of urine collected, dried, and mailed on a paper matrix (MPS Test). To determine if this assay could be automated, a robotic instrument was programmed to accomplish the procedure; the pilot method simultaneously determined GAG and creatinine concentrations in 10 patient specimens/run. Each analyte is measured in 4 dilutions, thus increasing the operating range to cover a broad spectrum of normal and pathologic levels. Samples and reagents are mixed in a 96-well tray format in approximately 20 min, and densitometric measurements are recorded in less than 60 s. Optical density measurements are electronically transmitted to a desktop computer to select optimal dilutions, identify values above or below the level of reliability, make calculations, and print reports. This automated method was applied to 255 specimens from 101 subjects representing each of the MPS diseases-specifically, types I (n 5 126), II (n 5 47), III (n 5 48), IV (n 5 17), VI (n 5 14) and VII (n 5 3). This method discriminated pathologic elevations of GAG excretion of MPS patients particularly when multiple specimens were available. Patients with non-MPS lysosomal diseases had normal GAG excretion, except for a patient with fucosidosis who had markedly elevated levels. Automation of the direct DMB method provides the key technology necessary for newborn screening for MPS diseases.

Original languageEnglish (US)
Pages (from-to)56-64
Number of pages9
JournalMolecular Genetics and Metabolism
Issue number1
StatePublished - 2002

Bibliographical note

Funding Information:
This study is dedicated to Daniel Molinaro (March 12, 1984– August 18, 2001) and was supported by grants from the Daniel Molinaro Foundation (Orange, CA), Friends of Richard Rotelli (Rumford, RI), and the National Institutes of Health (PO1-HD32652). For contribution of specimens we are indebted to members of the MPS family support groups with collection facilitated by Marie Capobianco and Joan Cohen (National MPS Society, Inc., USA), Sheila Lee (Canadian Society for Mucopolysaccharide and Related Diseases Inc.), Mary O’Toole and Christine Lavery (Society for Mucopolysaccharide Diseases, UK), Denise Law and Ros Smith (Mucopolysaccharide & Related Diseases Society Australia Ltd.), and Marion Kraft (Gesellschaft für Muko-polysaccharidosen und Ahnliche Erkrankungen, Austria). The authors thank Scott Kleist and David Erickson for assistance in preparation of the manuscript. MPS test is a trademark of Zebraic Corporation. Collection of GAG specimens on a paper matrix and quantification with DMB are patented by the University of Minnesota.


  • Bone marrow transplantation
  • Enzyme replacement therapy
  • Gene therapy
  • Hurler syndrome
  • MPS Test
  • Maroteaux-Lamy syndrome
  • Morquio syndrome
  • Mucopolysaccharidosis
  • Newborn screening
  • Sanfilippo syndrome
  • Sly syndrome


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