In:
Clinical Chemistry, Oxford University Press (OUP), Vol. 52, No. 4 ( 2006-04-01), p. 643-649
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.
Type of Medium:
Online Resource
ISSN:
0009-9147
,
1530-8561
DOI:
10.1373/clinchem.2005.061838
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2006
