Abstract
Hunter disease (Mucopolysaccharidosis type II, MPS II) is an X-linked lysosomal storage disorder caused by deficiency of iduronate-2-sulfatase (IDS). Two main therapies have been reported for MPS II patients: enzyme-replacement therapy (ERT) and hematopoietic stem-cell transplantation (HSCT). Both treatment modalities have been shown to improve some symptoms, but the results with regard to cognitive functioning have been poor. Early initiation of therapy, i.e., before neurological symptoms have manifested, may alter cognitive outcome. The need for early identification makes Hunter disease a candidate for newborn screening (NBS). Our objective was to explore the use of a fluorometric assay that could be applicable for high-throughput analysis of IDS activity in dried blood spots (DBS). The median IDS activity in DBS samples from 1,426 newborns was 377 pmol/punch/17 h (range 78–1111). The IDS activity in one sample was repeatedly under the cutoff value (set at 20% of the median value), which would imply a recall rate of 0.07%. A sample from a clinically diagnosed MPS II individual, included in each 96-well test plate, had IDS activities well below the 20% cutoff value. Coefficients of variation in quality control samples with low, medium, and high IDS activities (190, 304, and 430 pmol/punch/17 h, respectively) were 12% to 16%. This small-scale pilot study shows that newborn screening for Hunter disease using a fluorometric assay in DBS is technically feasible with a fairly low recall rate. NBS may allow for identification of infants with Hunter disease before clinical symptoms become evident enabling early intervention.
Competing interests: None declared
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Abbreviations
- 4MU:
-
4-methylumbelliferrone
- BMT:
-
Bone marrow transplantation
- DBS:
-
Dried blood spot
- ERT:
-
Enzyme-replacement therapy
- HSCT:
-
Hematopoietic stem-cell transplantation
- IDS:
-
Iduronate-2-sulfatase
- MPS:
-
Mucopolysaccharidosis
- NBS:
-
Newborn screening
References
Boelens JJ, Aldenhoven M, Purtill D et al (2013) Outcomes of transplantation using various hematopoietic cell sources in children with Hurler syndrome after myeloablative conditioning. Blood 121:3981–3987
Burton BK, Giugliani R (2012) Diagnosing Hunter syndrome in pediatric practice: practical considerations and common pitfalls. Eur J Pediatr 171:631–639
Chiang S-C, Hwu W-L, Lee N-C, Hsu L-W, Chien Y-H (2012) Algorithm for Pompe disease newborn screening: results from the Taiwan screening program. Mol Gen Metab 106:281–286
Chien Y-H, Chiang S-C, Zhang XK et al (2008) Early detection of Pompe disease by newborn screening is feasible: results from the Taiwan screening program. Pediatrics 122:e39–45
Civallero G, Michelin K, de Mari J et al (2006) Twelve different enzyme assays on dried-blood filter paper samples for detection of patients with selected inherited lysosomal storage diseases. Clin Chim Acta 372:98–102
Dajnoki A, Mühl A, Fekete G et al (2008) Newborn screening for Pompe disease by measuring acid alpha-glucosidase activity using tandem mass spectrometry. Clin Chem 54:1624–1629
Dajnoki A, Fekete G, Keutzer J et al (2010) Newborn screening for Fabry disease by measuring GLA activity using tandem mass spectrometry. Clin Chim Acta 411:1428–1431
De Jesus VR, Zhang XK, Keutzer J et al (2009) Development and Evaluation of Quality Control Dried Blood Spot Materials in Newborn Screening for Lysosomal Storage Disorders. Clin Chem 55:158–164
Guffon N, Bertrand Y, Forest I, Fouilhoux A, Froissart R (2009) Bone marrow transplantation in children with Hunter syndrome: outcome after 7 to 17 years. J Pediatr 154:733–737
Holt JB, Poe MD, Escolar ML (2011) Natural progression of neurological disease in mucopolysaccharidosis type II. Pediatrics 127:e1258–1265
Krivit W (2004) Allogeneic stem cell transplantation for the treatment of lysosomal and peroxisomal metabolic diseases. Springer Semin Immunopathol 26:119–132
Marsden D, Levy H (2010) Newborn screening of lysosomal storage disorders. Clin Chem 56:1071–1079
Muenzer J, Bodamer O, Burton B et al (2012) The role of enzyme replacement therapy in severe Hunter syndrome-an expert panel consensus. Eur J Pediatr 171:181–188
Oemardien LF, Boer AM, Ruijter GJG et al (2011) Hemoglobin precipitation greatly improves 4-methylumbelliferone-based diagnostic assays for lysosomal storage diseases in dried blood spots. Mol Gen Metab 102:44–48
Orsini JJ, Morrissey MA, Slavin LN et al (2009) Implementation of newborn screening for Krabbe disease: population study and cutoff determination. Clin Biochem 42:877–884
Scarpa M, Almássy Z, Beck M et al (2011) Mucopolysaccharidosis type II: European recommendations for the diagnosis and multidisciplinary management of a rare disease. Orphanet J Rare Dis 6:72
Sista R, Eckhardt AE, Wang T, Séllos-Moura M, Pamula VK (2011) Rapid, single-step assay for Hunter syndrome in dried blood spots using digital microfluidics. Clin Chim Acta 412:1895–1897
Tanaka A, Okuyama T, Suzuki Y et al (2012) Long-term efficacy of hematopoietic stem cell transplantation on brain involvement in patients with mucopolysaccharidosis type II: a nationwide survey in Japan. Mol Gen Metab 107:513–520
Tolun AA, Graham C, Shi Q et al (2012) A novel fluorometric enzyme analysis method for Hunter syndrome using dried blood spots. Mol Gen Metab 105:519–521
Vellodi A, Young E, Cooper A, Lidchi V, Winchester B, Wraith JE (1999) Long-term follow-up following bone marrow transplantation for Hunter disease. J Inherit Metab Dis 22:638–648
Voznyi YV, Keulemans JL, van Diggelen OP (2001) A fluorimetric enzyme assay for the diagnosis of MPS II (Hunter disease). J Inherit Metab Dis 24:675–680
Wolfe BJ, Blanchard S, Sadilek M, Scott CR, Turecek F, Gelb MH (2011) Tandem mass spectrometry for the direct assay of lysosomal enzymes in dried blood spots: application to screening newborns for mucopolysaccharidosis II (Hunter Syndrome). Anal Chem 83:1152–1156
Wraith JE, Scarpa M, Beck M et al (2008) Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy. Eur J Pediatr 167:267–277
Zhou H, Fernhoff P, Vogt RF (2011) Newborn Bloodspot Screening for Lysosomal Storage Disorders. J Pediatr 159:7–13
Acknowledgments
This research was funded through Top Institute Pharma, Leiden, the Netherlands as part of project T6-208-1, “Sustainable orphan drug development through registries and monitoring”. The project was financially supported by Genzyme Corporation, the Dutch Health Care Insurance Board (College voor Zorgverzekeringen), Shire Corporation, the Dutch Steering Committee on Orphan Drugs, Erasmus MC University Medical Center, Utrecht University Medical Center, and the Academic Medical Center at the University of Amsterdam. The project steering committee included representatives of the Dutch Association for Neuromuscular Diseases and the Netherlands patients’ association for metabolic disorders VKS [Volwassenen en kinderen met stofwisselingsziekten].
The National Institute for Public Health and the Environment (RIVM) is gratefully acknowledged for donating newborn screening cards. The authors thank Dr Hui Zhou (Centers for Disease Control and Prevention, Atlanta, Georgia) for providing QC DBS.
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Communicated by: Maurizio Scarpa, M.D, Ph.D
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Conflict of Interest
Salaries of GJGR, DAG, and SSW were funded in part by a grant through Top Institute Pharma, which was financially supported by Genzyme Corporation, the Dutch Health Care Insurance Board (College voor Zorgverzekeringen), Shire Corporation, the Dutch Steering Committee on Orphan Drugs, Erasmus MC University Medical Center, Utrecht University Medical Center, and the Academic Medical Center at the University of Amsterdam. The corporate sponsors of this research played no role in the design of the study, review, and interpretation of data, or preparation or approval of the manuscript.
AMB, JvdB, ATvdP, LHE, and AJReuser declare that they have no conflict of interest.
Informed Consent
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000.
This study was approved by the Erasmus University Medical Center Institutional Review Board.
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G. Ruijter, A. van der Ploeg, S. Weinreich, and A. Reuser contributed to the planning, conduct, and reporting of the work described in the article.
D. Goudriaan, A. Boer, J van den Bosch, and L. Elvers contributed to the conduct and reporting of the work described in the article.
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Ruijter, G.J.G. et al. (2013). Newborn Screening for Hunter Disease: A Small-Scale Feasibility Study. In: Zschocke, J., Gibson, K., Brown, G., Morava, E., Peters, V. (eds) JIMD Reports, Volume 14. JIMD Reports, vol 14. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2013_279
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DOI: https://doi.org/10.1007/8904_2013_279
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