Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Herbst, Zackary M., Urdaneta, Leslie, Klein, Terri, Burton, Barbara K., Basheeruddin, Khaja, Liao, Hsuan-Chieh, Fuller, Maria, Gelb, Michael H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8884011/
https://www.ncbi.nlm.nih.gov/pubmed/35225932
http://dx.doi.org/10.3390/ijns8010009
_version_ 1784660072093188096
author Herbst, Zackary M.
Urdaneta, Leslie
Klein, Terri
Burton, Barbara K.
Basheeruddin, Khaja
Liao, Hsuan-Chieh
Fuller, Maria
Gelb, Michael H.
author_facet Herbst, Zackary M.
Urdaneta, Leslie
Klein, Terri
Burton, Barbara K.
Basheeruddin, Khaja
Liao, Hsuan-Chieh
Fuller, Maria
Gelb, Michael H.
author_sort Herbst, Zackary M.
collection PubMed
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.
format Online
Article
Text
id pubmed-8884011
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-88840112022-03-01 Evaluation of Two Methods for Quantification of Glycosaminoglycan Biomarkers in Newborn Dried Blood Spots from Patients with Severe and Attenuated Mucopolysaccharidosis Type II Herbst, Zackary M. Urdaneta, Leslie Klein, Terri Burton, Barbara K. Basheeruddin, Khaja Liao, Hsuan-Chieh Fuller, Maria Gelb, Michael H. Int J Neonatal Screen Article 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. MDPI 2022-01-21 /pmc/articles/PMC8884011/ /pubmed/35225932 http://dx.doi.org/10.3390/ijns8010009 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Herbst, Zackary M.
Urdaneta, Leslie
Klein, Terri
Burton, Barbara K.
Basheeruddin, Khaja
Liao, Hsuan-Chieh
Fuller, Maria
Gelb, Michael H.
Evaluation of Two Methods for Quantification of Glycosaminoglycan Biomarkers in Newborn Dried Blood Spots from Patients with Severe and Attenuated Mucopolysaccharidosis Type II
title Evaluation of Two Methods for Quantification of Glycosaminoglycan Biomarkers in Newborn Dried Blood Spots from Patients with Severe and Attenuated Mucopolysaccharidosis Type II
title_full Evaluation of Two Methods for Quantification of Glycosaminoglycan Biomarkers in Newborn Dried Blood Spots from Patients with Severe and Attenuated Mucopolysaccharidosis Type II
title_fullStr Evaluation of Two Methods for Quantification of Glycosaminoglycan Biomarkers in Newborn Dried Blood Spots from Patients with Severe and Attenuated Mucopolysaccharidosis Type II
title_full_unstemmed Evaluation of Two Methods for Quantification of Glycosaminoglycan Biomarkers in Newborn Dried Blood Spots from Patients with Severe and Attenuated Mucopolysaccharidosis Type II
title_short Evaluation of Two Methods for Quantification of Glycosaminoglycan Biomarkers in Newborn Dried Blood Spots from Patients with Severe and Attenuated Mucopolysaccharidosis Type II
title_sort evaluation of two methods for quantification of glycosaminoglycan biomarkers in newborn dried blood spots from patients with severe and attenuated mucopolysaccharidosis type ii
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8884011/
https://www.ncbi.nlm.nih.gov/pubmed/35225932
http://dx.doi.org/10.3390/ijns8010009
work_keys_str_mv AT herbstzackarym evaluationoftwomethodsforquantificationofglycosaminoglycanbiomarkersinnewborndriedbloodspotsfrompatientswithsevereandattenuatedmucopolysaccharidosistypeii
AT urdanetaleslie evaluationoftwomethodsforquantificationofglycosaminoglycanbiomarkersinnewborndriedbloodspotsfrompatientswithsevereandattenuatedmucopolysaccharidosistypeii
AT kleinterri evaluationoftwomethodsforquantificationofglycosaminoglycanbiomarkersinnewborndriedbloodspotsfrompatientswithsevereandattenuatedmucopolysaccharidosistypeii
AT burtonbarbarak evaluationoftwomethodsforquantificationofglycosaminoglycanbiomarkersinnewborndriedbloodspotsfrompatientswithsevereandattenuatedmucopolysaccharidosistypeii
AT basheeruddinkhaja evaluationoftwomethodsforquantificationofglycosaminoglycanbiomarkersinnewborndriedbloodspotsfrompatientswithsevereandattenuatedmucopolysaccharidosistypeii
AT liaohsuanchieh evaluationoftwomethodsforquantificationofglycosaminoglycanbiomarkersinnewborndriedbloodspotsfrompatientswithsevereandattenuatedmucopolysaccharidosistypeii
AT fullermaria evaluationoftwomethodsforquantificationofglycosaminoglycanbiomarkersinnewborndriedbloodspotsfrompatientswithsevereandattenuatedmucopolysaccharidosistypeii
AT gelbmichaelh evaluationoftwomethodsforquantificationofglycosaminoglycanbiomarkersinnewborndriedbloodspotsfrompatientswithsevereandattenuatedmucopolysaccharidosistypeii