Development of an assay for the detection of mucopolysaccharidosis type VI patients using dried blood-spots

Leanne K. Hein; Peter J. Meikle; Caroline J. Dean; Michelle R. Bockmann; Dyane Auclair; John J. Hopwood; Doug A. Brooks

doi:10.1016/j.cccn.2004.10.009

Development of an assay for the detection of mucopolysaccharidosis type VI patients using dried blood-spots

Leanne K. Hein, Peter J. Meikle, Caroline J. Dean, Michelle R. Bockmann, Dyane Auclair, John J. Hopwood, Doug A. Brooks

Research output: Contribution to journal › Article › peer-review

29 Citations (Scopus)

Abstract

Background: Mucopolysaccharidosis type VI (MPS VI) is a lysosomal storage disorder (LSD), which is caused by a deficiency in the enzyme N-acetylgalactosamine 4-sulfatase (4-sulfatase). MPS VI is characterized by severe skeletal abnormalities, somatic tissue pathology and early death. Treatment possibilities include bone marrow transplantation (BMT) and enzyme replacement therapy (ERT; currently in phase III clinical trial). Early diagnosis of MPS VI will allow treatment before the onset of irreversible pathology. Methods: Sensitive immune assays have been developed to detect 4-sulfatase protein and activity in normal control and MPS VI blood-spots. Results: Dried blood-spots from MPS VI patients contained no detectable 4-sulfatase protein and activity, compared to 3.5-21 μg/L of 4-sulfatase protein and 291-1298 nmol/min/L of activity for normal human controls. In this evaluation study, the assay was sensitive and 100% specific, allowing reliable detection of individuals with MPS VI. Conclusions: The assays reported here have the potential to detect MPS VI patients using dried blood-spots.

Original language	English
Pages (from-to)	67-74
Number of pages	8
Journal	Clinica Chimica Acta
Volume	353
Issue number	1-2
DOIs	https://doi.org/10.1016/j.cccn.2004.10.009
Publication status	Published or Issued - Mar 2005

Keywords

Blood-spots
Immune assay
Lysosomal storage disorder
Maroteaux-Lamy syndrome
Mucopolysaccharidosis type VI
N-Acetylgalactosamine 4-sulfatase

ASJC Scopus subject areas

Biochemistry
Clinical Biochemistry
Biochemistry, medical

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10.1016/j.cccn.2004.10.009

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@article{618556df058d4e50bf3d4b4744605318,

title = "Development of an assay for the detection of mucopolysaccharidosis type VI patients using dried blood-spots",

abstract = "Background: Mucopolysaccharidosis type VI (MPS VI) is a lysosomal storage disorder (LSD), which is caused by a deficiency in the enzyme N-acetylgalactosamine 4-sulfatase (4-sulfatase). MPS VI is characterized by severe skeletal abnormalities, somatic tissue pathology and early death. Treatment possibilities include bone marrow transplantation (BMT) and enzyme replacement therapy (ERT; currently in phase III clinical trial). Early diagnosis of MPS VI will allow treatment before the onset of irreversible pathology. Methods: Sensitive immune assays have been developed to detect 4-sulfatase protein and activity in normal control and MPS VI blood-spots. Results: Dried blood-spots from MPS VI patients contained no detectable 4-sulfatase protein and activity, compared to 3.5-21 μg/L of 4-sulfatase protein and 291-1298 nmol/min/L of activity for normal human controls. In this evaluation study, the assay was sensitive and 100% specific, allowing reliable detection of individuals with MPS VI. Conclusions: The assays reported here have the potential to detect MPS VI patients using dried blood-spots.",

keywords = "Blood-spots, Immune assay, Lysosomal storage disorder, Maroteaux-Lamy syndrome, Mucopolysaccharidosis type VI, N-Acetylgalactosamine 4-sulfatase",

author = "Hein, {Leanne K.} and Meikle, {Peter J.} and Dean, {Caroline J.} and Bockmann, {Michelle R.} and Dyane Auclair and Hopwood, {John J.} and Brooks, {Doug A.}",

note = "Funding Information: The authors would like to thank Dr. David Ketteridge for collection of human blood-spots, Debbie Lang for europium labelling of the polyclonal antibody and Alison Whittle for performing column chromatography purification. This work was supported by a NH and MRC Program Grant and a NH and MRC Fellowship Grant in Australia.",

year = "2005",

month = mar,

doi = "10.1016/j.cccn.2004.10.009",

language = "English",

volume = "353",

pages = "67--74",

journal = "Clinica Chimica Acta",

issn = "0009-8981",

publisher = "Elsevier B.V.",

number = "1-2",

}

TY - JOUR

T1 - Development of an assay for the detection of mucopolysaccharidosis type VI patients using dried blood-spots

AU - Hein, Leanne K.

AU - Meikle, Peter J.

AU - Dean, Caroline J.

AU - Bockmann, Michelle R.

AU - Auclair, Dyane

AU - Hopwood, John J.

AU - Brooks, Doug A.

N1 - Funding Information: The authors would like to thank Dr. David Ketteridge for collection of human blood-spots, Debbie Lang for europium labelling of the polyclonal antibody and Alison Whittle for performing column chromatography purification. This work was supported by a NH and MRC Program Grant and a NH and MRC Fellowship Grant in Australia.

PY - 2005/3

Y1 - 2005/3

N2 - Background: Mucopolysaccharidosis type VI (MPS VI) is a lysosomal storage disorder (LSD), which is caused by a deficiency in the enzyme N-acetylgalactosamine 4-sulfatase (4-sulfatase). MPS VI is characterized by severe skeletal abnormalities, somatic tissue pathology and early death. Treatment possibilities include bone marrow transplantation (BMT) and enzyme replacement therapy (ERT; currently in phase III clinical trial). Early diagnosis of MPS VI will allow treatment before the onset of irreversible pathology. Methods: Sensitive immune assays have been developed to detect 4-sulfatase protein and activity in normal control and MPS VI blood-spots. Results: Dried blood-spots from MPS VI patients contained no detectable 4-sulfatase protein and activity, compared to 3.5-21 μg/L of 4-sulfatase protein and 291-1298 nmol/min/L of activity for normal human controls. In this evaluation study, the assay was sensitive and 100% specific, allowing reliable detection of individuals with MPS VI. Conclusions: The assays reported here have the potential to detect MPS VI patients using dried blood-spots.

AB - Background: Mucopolysaccharidosis type VI (MPS VI) is a lysosomal storage disorder (LSD), which is caused by a deficiency in the enzyme N-acetylgalactosamine 4-sulfatase (4-sulfatase). MPS VI is characterized by severe skeletal abnormalities, somatic tissue pathology and early death. Treatment possibilities include bone marrow transplantation (BMT) and enzyme replacement therapy (ERT; currently in phase III clinical trial). Early diagnosis of MPS VI will allow treatment before the onset of irreversible pathology. Methods: Sensitive immune assays have been developed to detect 4-sulfatase protein and activity in normal control and MPS VI blood-spots. Results: Dried blood-spots from MPS VI patients contained no detectable 4-sulfatase protein and activity, compared to 3.5-21 μg/L of 4-sulfatase protein and 291-1298 nmol/min/L of activity for normal human controls. In this evaluation study, the assay was sensitive and 100% specific, allowing reliable detection of individuals with MPS VI. Conclusions: The assays reported here have the potential to detect MPS VI patients using dried blood-spots.

KW - Blood-spots

KW - Immune assay

KW - Lysosomal storage disorder

KW - Maroteaux-Lamy syndrome

KW - Mucopolysaccharidosis type VI

KW - N-Acetylgalactosamine 4-sulfatase

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U2 - 10.1016/j.cccn.2004.10.009

DO - 10.1016/j.cccn.2004.10.009

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AN - SCOPUS:13444282110

SN - 0009-8981

VL - 353

SP - 67

EP - 74

JO - Clinica Chimica Acta

JF - Clinica Chimica Acta

IS - 1-2

ER -

Development of an assay for the detection of mucopolysaccharidosis type VI patients using dried blood-spots

Abstract

Keywords

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