Abstract
Newborn screening for classical galactosemia in the Netherlands is performed by five laboratories and is based on the measurement of galactose 1-phosphate-uridyltransferase (GALT) activity and total galactose (TGAL) in heel prick blood spots. Unexpected problems with the GALT assay posed a challenge to switch to a new assay. The aim of this study was to make an analytical and clinical evaluation of GALT assays to replace the current assay and to establish new cut-off values (COVs).
First, the manual assay from PerkinElmer (NG-1100) and the GSP assay were compared by analyzing 626 anonymous heel prick samples in parallel. Secondly, a manual GSP method was evaluated and 2,052 samples were compared with the automated GSP assay. Finally, a clinical evaluation was performed by collecting data from 93 referred newborns.
No satisfactory correlation was observed between GALT activity measured with the manual NG-1100 assay and the automated GSP assay. An acceptable correlation was found between the manual and automated GSP assay. Intra- and inter-assay variation of the automated GSP were 1.8–10.0% and 3.1–13.9%, respectively. Evaluation of clinical data demonstrated that adjusting the COVs for GALT to 2.0 U/dl and TGAL to 1,100 μmol/l improved specificity of screening for classical galactosemia.
An assay designed for automated processing to measure GALT activity in heel prick samples works equally well when processed manually. We therefore adopted both methods in the Dutch screening laboratories. As a result of this evaluation new COVs for GALT and TGAL have been introduced and are valid from July 2015.
E.A. Kemper and A. Boelen contributed equally to the preparation of this manuscript.
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Acknowledgements
This project would have been impossible without the help of many people involved in the Dutch newborn screening organization. This work was performed within the framework of the Dutch newborn screening organization, which is coordinated by the Centre for Population screening (RIVM – Mrs Eugenie Dekkers, programme director). We especially thank the two newborn screening laboratories in Zwolle and Tilburg, two of the five screening laboratories that were not mentioned in the text but made a significant contribution to collect data for this study.
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Communicated by: Piero Rinaldo, MD, PhD
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Take-Home Message
A new method for measuring GALT activity for newborn screening was introduced in the Netherlands and has led to new COVs in newborn screening for classical galactosemia and may lower referral rates.
Contributions of Individual Authors
Boelen A: Conception and design, data analysis and interpretation of data, drafting and revising article.
Kemper EA: Conception and design, data analysis and interpretation of data, drafting and revising article.
Bosch AM: Interpretation of data, professional consultation, revising article.
van Veen-Sijne M: Acquisition of data, revising article.
van Rijswijk CN: Acquisition of data, revising article.
Bouva MJ: Acquisition of data, revising article.
Fingerhut R: Acquisition of data, professional consultation, revising article.
Schielen PCJI: Conception and design, interpretation of data, drafting and revising article.
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Schielen PCJI
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Anita Boelen, Evelien Kemper, Annet Bosch, Marja van Veen, Carolien van Rijswijk, Marelle Bouva, Ralph Fingerhut, and Peter Schielen declare that they have no conflict of interest. With regard to the mandatory submission of the Conflict of Interest Disclosure Form, please see the following section on “Competing Interests”.
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Kemper, E.A. et al. (2016). Establishing New Cut-Off Limits for Galactose 1-Phosphate-Uridyltransferase Deficiency for the Dutch Newborn Screening Programme. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 32. JIMD Reports, vol 32. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2016_560
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DOI: https://doi.org/10.1007/8904_2016_560
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