Fluorimetric assays for N-acetylgalactosamine-6-sulfatase and arylsulfatase B based on the natural substrates for confirmation of mucopolysaccharidoses types IVA and VI

Arun Babu Kumar, Zdenek Spacil, Farideh Ghomashchi, Sophia Masi, Tomomi Sumida, Makoto Ito, Frantisek Turecek, C. Ronald Scott, Michael H. Gelb

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: Treatments have been developed for mucopolysaccharidoses IVA (MPS IVA) and MPS VI suggesting the need for eventual newborn screening. Biochemical enzyme assays are important for diagnosis. Previously reported fluorimetric assays of the relevant enzymes are based on substrates with poor activity or specificity. Methods: We developed new fluorimetric assays for N-acetylgalactosamine-6-sulfatase (GALNS) and arylsulfatase B (ARSB) based on the natural substrates, N-acetylgalactosamine-6-sulfate (and 4-sulfate), which have improved activity and specificity toward the relevant enzymes. The new substrates were tested on dried blood spots on newborn screening cards, and assays showed acceptable linearity in response with the amount of enzyme present (using quality control samples). Results: When tested on dried blood spots from random newborns and affected patients, the assays showed good discrimination between the 2 sample groups. Conclusions: The analytical range of the new fluorimetric assays, defined as the ratio of enzyme-dependent-to-enzyme-independent assay response, is likely to be insufficient to use these assays for newborn screening. Rather, these new fluorimetric assays should be useful in a diagnostic lab to confirm a diagnosis via biochemical enzyme testing.

Original languageEnglish
Pages (from-to)125-128
Number of pages4
JournalClinica Chimica Acta
Volume451
DOIs
Publication statusPublished - Dec 7 2015

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N-acetylglucosamine-6-sulfatase
Mucopolysaccharidosis VI
N-Acetylgalactosamine-4-Sulfatase
Mucopolysaccharidosis IV
Acetylgalactosamine
Assays
Enzyme Assays
Newborn Infant
Substrates
Enzymes
Mucopolysaccharidoses
Screening
Quality Control
Sulfates
Blood

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Clinical Biochemistry
  • Biochemistry, medical

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Fluorimetric assays for N-acetylgalactosamine-6-sulfatase and arylsulfatase B based on the natural substrates for confirmation of mucopolysaccharidoses types IVA and VI. / Kumar, Arun Babu; Spacil, Zdenek; Ghomashchi, Farideh; Masi, Sophia; Sumida, Tomomi; Ito, Makoto; Turecek, Frantisek; Scott, C. Ronald; Gelb, Michael H.

In: Clinica Chimica Acta, Vol. 451, 07.12.2015, p. 125-128.

Research output: Contribution to journalArticle

Kumar, Arun Babu ; Spacil, Zdenek ; Ghomashchi, Farideh ; Masi, Sophia ; Sumida, Tomomi ; Ito, Makoto ; Turecek, Frantisek ; Scott, C. Ronald ; Gelb, Michael H. / Fluorimetric assays for N-acetylgalactosamine-6-sulfatase and arylsulfatase B based on the natural substrates for confirmation of mucopolysaccharidoses types IVA and VI. In: Clinica Chimica Acta. 2015 ; Vol. 451. pp. 125-128.
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abstract = "Background: Treatments have been developed for mucopolysaccharidoses IVA (MPS IVA) and MPS VI suggesting the need for eventual newborn screening. Biochemical enzyme assays are important for diagnosis. Previously reported fluorimetric assays of the relevant enzymes are based on substrates with poor activity or specificity. Methods: We developed new fluorimetric assays for N-acetylgalactosamine-6-sulfatase (GALNS) and arylsulfatase B (ARSB) based on the natural substrates, N-acetylgalactosamine-6-sulfate (and 4-sulfate), which have improved activity and specificity toward the relevant enzymes. The new substrates were tested on dried blood spots on newborn screening cards, and assays showed acceptable linearity in response with the amount of enzyme present (using quality control samples). Results: When tested on dried blood spots from random newborns and affected patients, the assays showed good discrimination between the 2 sample groups. Conclusions: The analytical range of the new fluorimetric assays, defined as the ratio of enzyme-dependent-to-enzyme-independent assay response, is likely to be insufficient to use these assays for newborn screening. Rather, these new fluorimetric assays should be useful in a diagnostic lab to confirm a diagnosis via biochemical enzyme testing.",
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AU - Spacil, Zdenek

AU - Ghomashchi, Farideh

AU - Masi, Sophia

AU - Sumida, Tomomi

AU - Ito, Makoto

AU - Turecek, Frantisek

AU - Scott, C. Ronald

AU - Gelb, Michael H.

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