Specific GAG ratios in the diagnosis of mucopolysaccharidoses.

Mathis, Déborah; Prost, Jean-Christophe; Maeder, Gabriela; Arackal, Liya; Zhang, Haoyue; Kurth, Sandra; Freiburghaus, Katrin; Nuoffer, Jean-Marc (2024). Specific GAG ratios in the diagnosis of mucopolysaccharidoses. JIMD reports, 65(2), pp. 116-123. Wiley 10.1002/jmd2.12412

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Mucopolysaccharidoses (MPS) screening is tedious and still performed by analysis of total glycosaminoglycans (GAG) using 1,9-dimethylmethylene blue (DMB) photometric assay, although false positive and negative tests have been reported. Analysis of differentiated GAGs have been pursued classically by gel electrophoresis or more recently by quantitative LC-MS assays. Secondary elevations of GAGs have been reported in urinary tract infections (UTI). In this manuscript, we describe the diagnostic accuracy of urinary GAG measurements by LC-MS for MPS typing in 68 untreated MPS and mucolipidosis (ML) patients, 183 controls and 153 UTI samples. We report age-dependent reference values and cut-offs for chondroitin sulfate (CS), dermatan sulfate (DS), heparan sulfate (HS) and keratan sulfate (KS) and specific GAG ratios. The use of HS/DS ratio in combination to GAG concentrations normalized to creatinine improves the diagnostic accuracy in MPS type I, II, VI and VII. In total 15 samples classified to the wrong MPS type could be correctly assigned using HS/DS ratio. Increased KS/HS ratio in addition to increased KS improves discrimination of MPS type IV by excluding false positives. Some samples of UTI patients showed elevation of specific GAGs, mainly CS, KS and KS/HS ratio and could be misclassified as MPS type IV. Finally, DMB photometric assay performed in MPS and ML samples reveal four false negative tests (sensitivity of 94%). In conclusion, specific GAG ratios in complement to quantitative GAG values obtained by LC-MS enhance discrimination of MPS types. Exclusion of patients with UTI improve diagnostic accuracy in MPS IV but not in other types.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine > Endocrinology/Metabolic Disorders

UniBE Contributor:

Mathis, Déborah, Prost, Jean-Christophe, Kurth, Sandra, Freiburghaus, Katrin, Nuoffer, Jean-Marc


600 Technology > 610 Medicine & health








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Date Deposited:

19 Mar 2024 12:56

Last Modified:

19 Mar 2024 13:04

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Uncontrolled Keywords:

GAG LC–MS MPS chondroitin sulfate dermatan sulfate diagnosis dimethylmethylene blue dye‐binding (DMB) assay glycosaminoglycans heparan sulfate keratan sulfate mucopolysaccharidosis ratios reference values urinary tract infection





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