Work

Synthesis of the endogenous non-reducing end heparan sulfate disaccharides for newborn screening and diagnosis of mucopolysaccharidosis types I and II

Year: 2026

Type: article

Abstract: There is ongoing newborn screening (NBS) for mucopolysaccharidoses types I and II (MPS I and MPS II) because initiation of treatment early in life leads to better clinical outcomes. NBS starts with measurement of the relevant enzymatic activities in dried blood spots (DBS) on NBS cards. A second-tier test is carried out to eliminate false positives when enzymatic activity is low. In MPS I and MPS II, heparan sulfate accumulates, and previous studies have shown that the non-reducing end disaccharide fragments found endogenously in patient DBS and urine are elevated in patients but not in false positives. The proposed biomarker for MPS I is l-iduronic acid α(1,4)-linked to N-acetyl-d-glucosamine-6-sulfate, and the proposed biomarker for MPS II is l-iduronic acid(2-sulfate) α(1,4)-linked to N-acetyl-d-glucosamine. We now report the total synthesis of these candidate biomarkers for the first time and show by liquid chromatography-tandem mass spectrometry that they are identical to the analytes that accumulate in urine from MPS I and MPS II patients. The biomarkers were also prepared in heavy isotope labeled form so that they can be added to samples as internal standards. These reagents will allow for the first time the absolute moles of biomarkers to be determined in patient samples.

Source: Carbohydrate Research

DOI: 10.1016/j.carres.2026.110100

Authors: Gurpreet Singh, Sachin Popat Gholap, Sanghyun Lim, Zackary M. Herbst, Michael H. Gelb

Institution: University of Washington

Language: English

Topic: Lysosomal Storage Disorders Research

Subfield: Genetics (clinical)

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,800