Evaluation of Two Methods for Quantification of Glycosaminoglycan Biomarkers in Newborn Dried Blood Spots from Patients with Severe and Attenuated Mucopolysaccharidosis Type II

• Published in: International journal of neonatal screening Vol. 8; no. 1; p. 9
• Main Authors: Herbst, Zackary M, Urdaneta, Leslie, Klein, Terri, Burton, Barbara K, Basheeruddin, Khaja, Liao, Hsuan-Chieh, Fuller, Maria, Gelb, Michael H
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21.01.2022; MDPI
• Subjects: Acids; biochemical genetics; Biomarkers; Enzymes; Genetic disorders; Genotype & phenotype; glycosaminoglycans; Heparan sulfate; Hunter syndrome; Laboratories; Mass spectrometry; Medical screening; Metabolic disorders; Methods; mucopolysaccharidosis; newborn screening; Patients; Scientific imaging; Urine; United States > US; Illinois; glycosaminoglycans; mucopolysaccharidosis; Hunter syndrome; mass spectrometry; biochemical genetics; newborn screening
• ISSN: 2409-515X; 2409-515X
• DOI: 10.3390/ijns8010009

All newborn screening (NBS) for mucopolysaccharidosis-I and -II (MPS-I and MPS-II) is carried out via the measurement of α-iduronidase (IDUA) and iduronate-2-sulfatase (IDS) enzymatic activity, respectively, in dried blood spots (DBS). The majority of low enzyme results are due to pseudodeficiencies, and data from recent MPS-II population screenings and studies from the Mayo Clinic show that the false positive rate can be dramatically reduced by the inclusion of a second-tier analysis of glycosaminoglycans (GAGs) in DBS as part of NBS. In the present study, which focused on MPS-II, we obtained newborn DBS from 17 patients with severe MPS-II, 1 with attenuated MPS-II, and 6 patients with various IDS pseudodeficiencies. These samples were submitted to two different GAG mass spectrometry analyses in a comparative study: (1) internal disaccharide biomarkers and (2) endogenous biomarkers. For both of these methods, the biomarker levels in six patients with pseudodeficiencies were below the range measured in MPS-II patients. One patient with attenuated MPS-II was not distinguishable from severe disease patients, but all MPS-II patients were distinguishable from the reference range using both methods. The minimal differential factor (lowest GAG marker level in MPS-II samples divided by highest level in the reference range of 60 random newborns) was 3.01-fold for the internal disaccharide method. The endogenous biomarker method demonstrated an improved minimum differential of 5.41-fold. The minimum differential factors between MPS-II patients and patients with pseudodeficiencies for the internal disaccharide and endogenous biomarker methods were 3.77-fold and 2.06-fold, respectively. This study supports use of the second-tier GAG analysis of newborn DBS, especially the endogenous disaccharide method, as part of NBS to reduce the false positive rate.