Development of a newborn screening tool for mucopolysaccharidosis type I based on bivariate normal limits: Using glycosaminoglycan and alpha-L-iduronidase determinations on dried blood spots to predict symptoms

JIMD Reports
Thomas J LanganShunji Tomatsu

Abstract

Current newborn screening (NBS) for mucopolysaccharidosis type I (MPSI) has very high false positive rates and low positive predictive values (PPVs). To improve the accuracy of presymptomatic prediction for MPSI, we propose an NBS tool based on known biomarkers, alpha-L-iduronidase enzyme activity (IDUA) and level of the glycosaminoglycan (GAG) heparan sulfate (HS). We developed the NBS tool using measures from dried blood spots (DBS) of 5000 normal newborns from Gifu Prefecture, Japan. The tool's predictive accuracy was tested on the newborn DBS from these infants and from seven patients who were known to have early-onset MPSI (Hurler's syndrome). Bivariate analyses of the standardized natural logarithms of IDUA and HS levels were employed to develop the tool. Every case of early-onset MPSI was predicted correctly by the tool. No normal newborn was incorrectly identified as having early-onset MPSI, whereas 12 normal newborns were so incorrectly identified by the Gifu NBS protocol. The PPV was estimated to be 99.9%. Bivariate analysis of IDUA with HS in newborn DBS can accurately predict early MPSI symptoms, control false positive rates, and enhance presymptomatic treatment. This bivariate analysis-based approach, which was dev...Continue Reading

References

Mar 1, 1985·American Journal of Medical Genetics·M RoubicekJ Spranger
Jul 9, 1994·BMJ : British Medical Journal·D G Altman, J M Bland
Feb 15, 2001·The New England Journal of Medicine·E D KakkisE F Neufeld
Dec 22, 2010·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Michele A Lloyd-Puryear, Amy Brower
Feb 18, 2011·Genetics in Medicine : Official Journal of the American College of Medical Genetics·David M S McHughWendy M Zakowicz
Jul 19, 2013·Molecular Genetics and Metabolism·Shunji TomatsuTadao Orii
Jan 7, 2014·Molecular Genetics and Metabolism·Joseph Muenzer
Aug 12, 2014·Annals of Neurology·Michele D PoeMaria L Escolar
May 14, 2016·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Melissa P WassersteinMichele Caggana
Sep 18, 2016·Journal of Neuroscience Research·Randy L CarterThomas J Langan
Oct 9, 2016·Journal of Inherited Metabolic Disease·Francyne KubaskiShunji Tomatsu
Jul 22, 2017·The Journal of Pediatrics·Barbara K BurtonGeorge Dizikes
Nov 10, 2017·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Melissa M Minter BaergPiero Rinaldo
Nov 17, 2017·Journal of Inherited Metabolic Disease·Alberto B BurlinaAlessandro P Burlina
May 22, 2018·Molecular Genetics and Metabolism·Shaukat A KhanShunji Tomatsu
May 29, 2018·Orphanet Journal of Rare Diseases·Chih-Kuang ChuangShuan-Pei Lin
May 31, 2018·JAMA Pediatrics·Patrick V HopkinsSharmini Rogers
Jul 31, 2018·Molecular Genetics and Metabolism·Molly StapletonShunji Tomatsu
Aug 11, 2018·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Anne Marie Comeau
Aug 11, 2018·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Melissa P WassersteinJoseph J Orsini
Aug 14, 2018·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Aaron J GoldenbergUNKNOWN Bioethics and Legal Workgroup of the Newborn Screening Translational Research Network
Dec 14, 2018·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Thomas J LanganRandy L Carter
Feb 18, 2019·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Madeleine TaylorShunji Tomatsu

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Citations

May 21, 2020·Clinical Chemistry and Laboratory Medicine : CCLM·Giulia PoloAlberto B Burlina
Nov 18, 2020·International Journal of Neonatal Screening·Seok-Ho YuRichard Steet
Feb 14, 2021·Diagnostics·Betul ÇelikShaukat A Khan
Jun 25, 2021·Neuroscience Letters·Melissa P WassersteinMichael H Gelb

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Methods Mentioned

BETA
genotyping

Software Mentioned

R
MPSI
HS
IDUA
BVNL
Gifu

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