Detection of Mucopolysaccharidosis Type II by Measurement of Iduronate-2-Sulfatase in Dried Blood Spots and Plasma Samples
Open Access
- 1 April 2006
- journal article
- Published by Oxford University Press (OUP) in Clinical Chemistry
- Vol. 52 (4), 643-649
- https://doi.org/10.1373/clinchem.2005.061838
Abstract
Background: Mucopolysaccharidosis type II (MPS II) is a lysosomal storage disorder related to a deficiency in the enzyme iduronate-2-sulfatase (IDS). Clinical trials of enzyme replacement therapy are in progress, but effective treatment will require screening assays to enable early detection and diagnosis of MPS II. Our study evaluated the diagnostic accuracy of IDS protein and enzyme activity measurements in dried blood spots and plasma. Methods: We collected dried-blood-spot and plasma samples from unaffected control individuals and from MPS II patients. We measured IDS protein concentration with a 2-step time-delayed dissociation-enhanced lanthanide fluorescence immunoassay. To measure enzyme activity, we immobilized anti-IDS antibody on microtiter plates to capture the enzyme and measured its activity with the fluorogenic substrate 4-methylumbelliferyl sulfate. Results: Dried-blood-spot samples from MPS II patients showed an almost total absence of IDS activity (0–0.075 μmol · h−1 · L−1) compared with control blood spots (0.5–4.7 μmol · h−1 · L−1) and control plasma (0.17–8.1 μmol · h−1 · L−1). A dried-blood-spot sample from only 1 of 12 MPS II patients had detectable concentrations of IDS protein (24.8 μg/L), but no IDS protein was detected in plasma from MPS II patients. Ranges for IDS protein in control samples were 25.8–153 μg/L for blood spots and 22.8–349.4 μg/L for plasma. Conclusion: Measurement of the IDS protein concentration and enzyme activity (as measured by a simple fluorogenic assay with an immune capture technique) enables identification of the majority of MPS II patient samples from both dried blood spots and plasma samples.Keywords
This publication has 27 references indexed in Scilit:
- Direct Comparison of Measures of Endurance, Mobility, and Joint Function During Enzyme-Replacement Therapy of Mucopolysaccharidosis VI (Maroteaux-Lamy Syndrome): Results After 48 Weeks in a Phase 2 Open-Label Clinical Study of Recombinant Human N-Acetylgalactosamine 4-SulfatasePublished by American Academy of Pediatrics (AAP) ,2005
- Prediction of neuropathology in mucopolysaccharidosis I patientsMolecular Genetics and Metabolism, 2005
- Gaucher disease: alendronate disodium improves bone mineral density in adults receiving enzyme therapyBlood, 2004
- Long-Term Safety and Efficacy of Enzyme Replacement Therapyfor Fabry DiseaseAmerican Journal of Human Genetics, 2004
- Enzyme replacement therapy for mucopolysaccharidosis I: a randomized, double-blinded, placebo-controlled, multinational study of recombinant human α-L-iduronidase (laronidase)The Journal of Pediatrics, 2004
- Iduronate-2-sulphatase protein detection in plasma from mucopolysaccharidosis type II patientsMolecular Genetics and Metabolism, 2004
- Human Gene Mutation Database (HGMD®): 2003 updateHuman Mutation, 2003
- Enzyme replacement therapy in mucopolysaccharidosis type II (Hunter syndrome): a preliminary reportActa Paediatrica, 2002
- Long‐term follow‐up following bone marrow transplantation for Hunter diseaseJournal of Inherited Metabolic Disease, 1999
- Mucopolysaccharidosis type II: Identification of six novel mutations in Italian patientsHuman Mutation, 1997