Simple steps to achieve harmonisation and standardisation of dried blood spot phenylalanine measurements and facilitate consistent management of patients with phenylketonuria

Carling, Rachel S., Barclay, Zoe, Cantley, Nathan, Ghansah, Nana, Hogg, Sarah L., Horman, Alistair, Moat, Stuart J., Cowen, Simon, Hopley, Chris, Deaves, Chloe and Whyte, Emily 2025. Simple steps to achieve harmonisation and standardisation of dried blood spot phenylalanine measurements and facilitate consistent management of patients with phenylketonuria. Clinical Chemistry and Laboratory Medicine 10.1515/cclm-2024-1367

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Abstract

Objectives Management of phenylketonuria (PKU) relies upon life-long monitoring of phenylalanine (Phe) in dried blood spots (DBS), thus comparability of measurements is important. The lack of harmonisation and standardisation between laboratories, combined with the variable quality of patient-collected DBS specimens, are currently preventing this from being achieved. A traceable, matrix-matched Phe certified reference material, common methodology and means to ensure patient collected DBS specimens are of consistent quality would improve comparability between laboratories. Methods Baseline inter-laboratory (n=15) variation of DBS Phe was determined by triplicate measurement of four DBS materials, on three days. Laboratories prepared and analysed these samples using their routine method of analysis. A sub-set of laboratories (n=5) repeated the process using a common sample preparation and instrument methodology (LC-MS/MS), and three different calibration approaches. Samples prepared on dried blood spot microsampling cards (DBS-MCs) from whole blood, value assigned for Phe concentration by National Measurement Laboratories (NML), were then analysed using the harmonised methodology. Results Inter-laboratory co-efficient of variation (CV) differed with calibration approach; internal calibration 27.7 %; in-house aqueous calibration 4.7 %; centrally distributed aqueous calibration, 2.1 %. Inter-laboratory CV was reduced from 8.7 to 2.1 % by using common sample preparation and LC-MS/MS methodology. No significant difference was observed between consensus and assigned values for Phe in the four materials (p>0.05). Conclusions This study demonstrates a simple approach to harmonising and standardising DBS Phe measurements, traceable to value assigned materials. Combined with the introduction of DBS-MCs to ensure specimen quality, clinical laboratories can achieve comparability of patient results over time.

Item Type:	Article
Status:	In Press
Schools:	Medicine
Publisher:	De Gruyter
ISSN:	1434-6621
Date of First Compliant Deposit:	13 February 2025
Date of Acceptance:	26 January 2025
Last Modified:	13 Feb 2025 16:00
URI:	https://orca.cardiff.ac.uk/id/eprint/176168

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