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Evaluation of Two Methods for Quantification of Glycosaminoglycan Biomarkers in Newborn Dried Blood Spots from Patients with Severe and Attenuated Mucopolysaccharidosis Type II
| Content Provider | MDPI |
|---|---|
| Author | Herbst, Zackary M. Urdaneta, Leslie Klein, Terri Burton, Barbara K. Basheeruddin, Khaja Liao, Hsuan-Chieh Fuller, Maria Gelb, Michael H. |
| Copyright Year | 2022 |
| Description | 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. |
| Starting Page | 9 |
| e-ISSN | 2409515X |
| DOI | 10.3390/ijns8010009 |
| Journal | International Journal of Neonatal Screening |
| Issue Number | 1 |
| Volume Number | 8 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2022-01-21 |
| Access Restriction | Open |
| Subject Keyword | International Journal of Neonatal Screening Biochemical Research Newborn Screening Glycosaminoglycans Mucopolysaccharidosis Hunter Syndrome Mass Spectrometry Biochemical Genetics |
| Content Type | Text |
| Resource Type | Article |
