Endogenous, non-reducing end glycosaminoglycan biomarkers are superior to internal disaccharide glycosaminoglycan biomarkers for newborn screening of mucopolysaccharidoses and GM1 gangliosidosis

Zackary M Herbst; Xinying Hong; Leslie Urdaneta; Terri Klein; Christine Waggoner; Hsuan-Chieh Liao; Francyne Kubaski; Roberto Giugliani; Maria Fuller; Michael H Gelb

doi:10.1016/j.ymgme.2023.107632

Endogenous, non-reducing end glycosaminoglycan biomarkers are superior to internal disaccharide glycosaminoglycan biomarkers for newborn screening of mucopolysaccharidoses and GM1 gangliosidosis

Mol Genet Metab. 2023 Sep-Oct;140(1-2):107632. doi: 10.1016/j.ymgme.2023.107632. Epub 2023 Jun 24.

Authors

Affiliations

¹ Department of Chemistry, University of Washington, Seattle, WA 98195, USA. Electronic address: zherbst@uw.edu.
² Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA. Electronic address: hongx@chop.edu.
³ National MPS Society, P.O. Box 14686, Durham, NC 27709-4686, USA. Electronic address: leslie@mpssociety.org.
⁴ National MPS Society, P.O. Box 14686, Durham, NC 27709-4686, USA. Electronic address: terri@mpssociety.org.
⁵ Cure GM1 Foundation, P.O. Box 6890, Albany, CA 94706, USA. Electronic address: christine@curegm1.org.
⁶ Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USA. Electronic address: liaohc6@uw.edu.
⁷ Greenwood Genetic Center, Biochemical Genetics Laboratory, Greenwood, SC 29646, USA. Electronic address: fkubaski@ggc.org.
⁸ Programa de Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. Electronic address: rgiugliani@hcpa.edu.br.
⁹ Genetics and Molecular Pathology, SA Pathology at Women's and Children's Hospital, Adelaide Medical School and School of Biological Sciences University of Adelaide, North Adelaide 5006, Australia. Electronic address: maria.fuller@adelaide.edu.au.
¹⁰ Department of Chemistry, University of Washington, Seattle, WA 98195, USA; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA. Electronic address: gelb@uw.edu.

PMID: 37407323
PMCID: PMC10748792 (available on 2024-09-01)
DOI: 10.1016/j.ymgme.2023.107632

Abstract

Measurement of enzymatic activity in newborn dried blood spots (DBS) is the preferred first-tier method in newborn screening (NBS) for mucopolysaccharidoses (MPSs). Our previous publications on glycosaminoglycan (GAG) biomarker levels in DBS for mucopolysaccharidosis type 1 (MPS-I) and MPS-II demonstrated that second-tier GAG biomarker analysis can dramatically reduce the false positive rate in NBS. In the present study, we evaluate two methods for measuring GAG biomarkers in seven MPS types and GM1 gangliosidosis. We obtained newborn DBS from patients with MPS-IIIA-D, -IVA, -VI, -VII, and GM1 gangliosidosis. These samples were analyzed via two GAG mass spectrometry methods: (1) The internal disaccharide biomarker method; (2) The endogenous non-reducing end (NRE) biomarker method. This study supports the use of second-tier GAG analysis of newborn DBS by the endogenous NRE biomarker method, as part of NBS to reduce the false positive rate.

Keywords: Biochemical genetics; GM1 gangliosidosis; Glycosaminoglycans; Mass spectrometry; Mucopolysaccharidosis; Newborn screening.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Biomarkers
Disaccharides
Gangliosidosis, GM1*
Glycosaminoglycans
Humans
Infant, Newborn
Mucopolysaccharidoses* / diagnosis
Neonatal Screening / methods
Tandem Mass Spectrometry / methods

Substances

Glycosaminoglycans
Disaccharides
Biomarkers

Grants and funding

R01 DK067859/DK/NIDDK NIH HHS/United States