Open AccessMonitoring phenylalanine concentrations in the follow‐up of phenylketonuria patients: An inventory of pre‐analytical and analytical variation
Author(s) -
Coene Karlien L. M.,
Timmer Corrie,
Goorden Susan M. I.,
Hoedt Amber E.,
Kluijtmans Leo A. J.,
Janssen Mirian C. H.,
Rennings Alexander J. M.,
Prinsen Hubertus C. M. T.,
Wamelink Mirjam M. C.,
Ruijter George J. G.,
KörverKeularts Irene M. L. W.,
HeinerFokkema M. Rebecca,
Spronsen Francjan J.,
Hollak Carla E.,
Vaz Frédéric M.,
Bosch Annet M.,
Huigen Marleen C. D. G.
Publication year - 2021
Publication title -
jimd reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.412
H-Index - 25
ISSN - 2192-8312
DOI - 10.1002/jmd2.12186
Subject(s) - dried blood spot , phenylalanine , dried blood , chemistry , venous blood , plasma concentration , medicine , chromatography , amino acid , biochemistry
Background Reliable measurement of phenylalanine (Phe) is a prerequisite for adequate follow‐up of phenylketonuria (PKU) patients. However, previous studies have raised concerns on the intercomparability of plasma and dried blood spot (DBS) Phe results. In this study, we made an inventory of differences in (pre‐)analytical methodology used for Phe determination across Dutch laboratories, and compared DBS and plasma results. Methods Through an online questionnaire, we assessed (pre‐)analytical Phe measurement procedures of seven Dutch metabolic laboratories. To investigate the difference between plasma and DBS Phe, participating laboratories received simultaneously collected plasma‐DBS sets from 23 PKU patients. In parallel, 40 sample sets of DBS spotted from either venous blood or capillary fingerprick were analyzed. Results Our data show that there is no consistency on standard operating procedures for Phe measurement. The association of DBS to plasma Phe concentration exhibits substantial inter‐laboratory variation, ranging from a mean difference of −15.5% to +30.6% between plasma and DBS Phe concentrations. In addition, we found a mean difference of +5.8% in Phe concentration between capillary DBS and DBS prepared from venous blood. Conclusions The results of our study point to substantial (pre‐)analytical variation in Phe measurements, implicating that bloodspot Phe results should be interpreted with caution, especially when no correction factor is applied. To minimize variation, we advocate pre‐analytical standardization and analytical harmonization of Phe measurements, including consensus on application of a correction factor to adjust DBS Phe to plasma concentrations.