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

• Published in: Molecular genetics and metabolism Vol. 140; no. 1-2; p. 107632
• Main Authors: Herbst, Zackary M., Hong, Xinying, Urdaneta, Leslie, Klein, Terri, Waggoner, Christine, Liao, Hsuan-Chieh, Kubaski, Francyne, Giugliani, Roberto, Fuller, Maria, Gelb, Michael H.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2023
• Subjects: Biochemical genetics; Biomarkers; Disaccharides; Gangliosidosis, GM1; Glycosaminoglycans; GM1 gangliosidosis; Humans; Infant, Newborn; Mass spectrometry; Mucopolysaccharidoses - diagnosis; Mucopolysaccharidosis; Neonatal Screening - methods; Newborn screening; Tandem Mass Spectrometry - methods; Newborn screening; Mucopolysaccharidosis; Biochemical genetics; Glycosaminoglycans; GM1 gangliosidosis; Mass spectrometry
• ISSN: 1096-7192; 1096-7206; 1096-7206
• DOI: 10.1016/j.ymgme.2023.107632

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.