Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Jan;40(1):151-158.
doi: 10.1007/s10545-016-9981-6. Epub 2016 Oct 7.

Newborn screening for mucopolysaccharidoses: a pilot study of measurement of glycosaminoglycans by tandem mass spectrometry

Francyne Kubaski  1   2 , Robert W Mason  1   2 , Akiko Nakatomi  3 , Haruo Shintaku  4 , Li Xie  1 , Naomi N van Vlies  5 , Heather Church  6 , Roberto Giugliani  7 , Hironori Kobayashi  8 , Seiji Yamaguchi  8 , Yasuyuki Suzuki  9 , Tadao Orii  10 , Toshiyuki Fukao  10 , Adriana M Montaño  11   12 , Shunji Tomatsu  13   14   15
Affiliations

Newborn screening for mucopolysaccharidoses: a pilot study of measurement of glycosaminoglycans by tandem mass spectrometry

Francyne Kubaski et al. J Inherit Metab Dis. 2017 Jan.

Abstract

Background: Mucopolysaccharidoses (MPS) are a group of inborn errors of metabolism that are progressive and usually result in irreversible skeletal, visceral, and/or brain damage, highlighting a need for early diagnosis.

Methods: This pilot study analyzed 2862 dried blood spots (DBS) from newborns and 14 DBS from newborn patients with MPS (MPS I, n = 7; MPS II, n = 2; MPS III, n = 5). Disaccharides were produced from polymer GAGs by digestion with chondroitinase B, heparitinase, and keratanase II. Heparan sulfate (0S, NS), dermatan sulfate (DS) and mono- and di-sulfated KS were measured by liquid chromatography tandem mass spectrometry (LC-MS/MS). Median absolute deviation (MAD) was used to determine cutoffs to distinguish patients from controls. Cutoffs were defined as median + 7× MAD from general newborns.

Results: The cutoffs were as follows: HS-0S > 90 ng/mL; HS-NS > 23 ng/mL, DS > 88 ng/mL; mono-sulfated KS > 445 ng/mL; di-sulfated KS > 89 ng/mL and ratio di-KS in total KS > 32 %. All MPS I and II samples were above the cutoffs for HS-0S, HS-NS, and DS, and all MPS III samples were above cutoffs for HS-0S and HS-NS. The rate of false positives for MPS I and II was 0.03 % based on a combination of HS-0S, HS-NS, and DS, and for MPS III was 0.9 % based upon a combination of HS-0S and HS-NS.

Conclusions: Combination of levels of two or more different GAGs improves separation of MPS patients from unaffected controls, indicating that GAG measurements are potentially valuable biomarkers for newborn screening for MPS.

PubMed Disclaimer

Figures

Figure 1
Figure 1
HS-0S in general newborns and MPS newborns Primary left y-axis represents solid bars for the number of general newborns (n=2862) among the different intervals; secondary right y-axis represents open bars for the number of MPS newborns (n=14) among the different intervals; dashed line represents the cutoff (median + 7× MAD for control newborns).
Figure 2
Figure 2
HS-NS in general newborns and MPS newborns Primary left y-axis represents solid bars for the number of general newborns (n=2862) among the different intervals; secondary right y-axis represents open bars for the number of MPS newborns (n=14) among the different intervals; dashed line represents the cutoff (median + 7× MAD for control newborns).
Figure 3
Figure 3
DS in general newborns and MPS newborns Primary left y-axis represents solid bars for the number of general newborns (n=2862) among the different intervals; secondary right y-axis represents open bars for the number of MPS newborns (n=14) among the different intervals; dashed line represents the cutoff (median + 7× MAD for control newborns).
Figure 4
Figure 4
Algorithm for two-tier newborn screening
See this image and copyright information in PMC

References

    1. Auclair D, Hopwood JJ, Brooks DA, et al. Replacement therapy in Mucopolysaccharidosis type VI: advantages of early onset of therapy. MGM. 2003;78:163–74. - PubMed
    1. Baldo G, Matte U, Artigalas O, et al. Placenta analysis of prenatally diagnosed patients reveals early GAG storage in mucopolysaccharidoses II and VI. MGM. 2011;103:197–8. - PubMed
    1. Baldo G, Mayer FQ, Martinelli BZ, et al. Enzyme replacement therapy started at birth improves outcome in difficult-to-treat organs in mucopolysaccharidosis I mice. MGM. 2013;109:33–40. - PubMed
    1. Beck M, Braun S, Coerdt W, et al. Fetal presentation of Morquio disease type A. Prenat Diagn. 1992;12:1019–9. - PubMed
    1. Blanchard S, Sadilek M, Scott CR, et al. Tandem mass spectrometry for the direct assay of lysosomal enzymes in dried blood spots: application to screening newborns for mucopolysaccharidosis I. Clin Chem. 2008;54:2067–70. - PMC - PubMed

Publication types

MeSH terms