Publication

Does the 48-hour BH4 loading test miss responsive PKU patients?

van Wegberg, A. M. J., Evers, R. A. F., van Dam, E., de Vries, M. C., Janssen, M. C. H., Heiner-Fokkema, M. R. & van Spronsen, F. J., Mar-2020, In : Molecular Genetics and Metabolism. 129, 3, p. 186-192 7 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

van Wegberg, A. M. J., Evers, R. A. F., van Dam, E., de Vries, M. C., Janssen, M. C. H., Heiner-Fokkema, M. R., & van Spronsen, F. J. (2020). Does the 48-hour BH4 loading test miss responsive PKU patients? Molecular Genetics and Metabolism, 129(3), 186-192. https://doi.org/10.1016/j.ymgme.2019.12.011

Author

van Wegberg, Annemiek M J ; Evers, Roeland A F ; van Dam, Esther ; de Vries, Maaike C ; Janssen, Mirian C H ; Heiner-Fokkema, M Rebecca ; van Spronsen, Francjan J. / Does the 48-hour BH4 loading test miss responsive PKU patients?. In: Molecular Genetics and Metabolism. 2020 ; Vol. 129, No. 3. pp. 186-192.

Harvard

van Wegberg, AMJ, Evers, RAF, van Dam, E, de Vries, MC, Janssen, MCH, Heiner-Fokkema, MR & van Spronsen, FJ 2020, 'Does the 48-hour BH4 loading test miss responsive PKU patients?', Molecular Genetics and Metabolism, vol. 129, no. 3, pp. 186-192. https://doi.org/10.1016/j.ymgme.2019.12.011

Standard

Does the 48-hour BH4 loading test miss responsive PKU patients? / van Wegberg, Annemiek M J; Evers, Roeland A F; van Dam, Esther; de Vries, Maaike C; Janssen, Mirian C H; Heiner-Fokkema, M Rebecca; van Spronsen, Francjan J.

In: Molecular Genetics and Metabolism, Vol. 129, No. 3, 03.2020, p. 186-192.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

van Wegberg AMJ, Evers RAF, van Dam E, de Vries MC, Janssen MCH, Heiner-Fokkema MR et al. Does the 48-hour BH4 loading test miss responsive PKU patients? Molecular Genetics and Metabolism. 2020 Mar;129(3):186-192. https://doi.org/10.1016/j.ymgme.2019.12.011


BibTeX

@article{6efbb51994bd40a4b0c5cb76ba913eff,
title = "Does the 48-hour BH4 loading test miss responsive PKU patients?",
abstract = "BACKGROUND: Phenylketonuria (PKU) is an inborn error of phenylalanine (Phe) metabolism. Besides dietary treatment, some patients are responsive to and treated with tetrahydrobiopterin (BH4). Our primary objective was to examine whether the 48-hour BH4 loading test misses BH4-responsive PKU patients. Secondary, we assessed if it would be beneficial to 1) use a cut-off value of 20{\%} Phe reduction instead of commonly used 30{\%}, and 2) extend the loading test to 7 days.METHODS: 24 patients with a 20-30{\%} decrease of blood Phe levels during their initial 48-hour BH4 loading test or at least one mutation associated with long-term BH4 responsiveness, were invited to participate. 22 of them underwent the 7-day BH4 loading test. During the BH4 loading test, BH4 was administered orally once daily for 7 days (20 mg/kg/day). Blood samples on filter paper were collected at 13 time points. Potential BH4 responders (≥20{\%} decrease in blood Phe concentrations at ≥1 moment within the first 48 h or ≥30{\%} at ≥1 moment during the entire test) underwent a treatment trial to assess true long-term responsiveness (≥30{\%} decrease of Phe levels compared to baseline and/or ≥50{\%} increase in natural protein tolerance in accordance with the Dutch guidelines before 2017). The duration of the treatment trial varied from 2 to 18 months.RESULTS: Of the 22 patients who completed the 7-day BH4 loading test, 2 were excluded, 8 had negative tests and 12 were considered to be potential BH4 responders. Of these 12 potential BH4-responsive PKU patients, 5 turned out to be false positive, 6 true-responder and 1 was withdrawn.CONCLUSION: Even though the 48-hour BH4 loading test has proven its efficacy in the past, a full week may be necessary to detect all responders. So, if blood Phe concentrations during the 48-hour BH4 test shows a clear tendency, but not sufficient decrease, a full week (with only measurements each 24 h) could be offered. A threshold of ≥20{\%} decrease within 48 h is not useful for predicting true BH4 responsiveness.",
author = "{van Wegberg}, {Annemiek M J} and Evers, {Roeland A F} and {van Dam}, Esther and {de Vries}, {Maaike C} and Janssen, {Mirian C H} and Heiner-Fokkema, {M Rebecca} and {van Spronsen}, {Francjan J}",
note = "Copyright {\circledC} 2020 The Authors. Published by Elsevier Inc. All rights reserved.",
year = "2020",
month = "3",
doi = "10.1016/j.ymgme.2019.12.011",
language = "English",
volume = "129",
pages = "186--192",
journal = "Molecular Genetics and Metabolism",
issn = "1096-7192",
publisher = "ACADEMIC PRESS INC ELSEVIER SCIENCE",
number = "3",

}

RIS

TY - JOUR

T1 - Does the 48-hour BH4 loading test miss responsive PKU patients?

AU - van Wegberg, Annemiek M J

AU - Evers, Roeland A F

AU - van Dam, Esther

AU - de Vries, Maaike C

AU - Janssen, Mirian C H

AU - Heiner-Fokkema, M Rebecca

AU - van Spronsen, Francjan J

N1 - Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2020/3

Y1 - 2020/3

N2 - BACKGROUND: Phenylketonuria (PKU) is an inborn error of phenylalanine (Phe) metabolism. Besides dietary treatment, some patients are responsive to and treated with tetrahydrobiopterin (BH4). Our primary objective was to examine whether the 48-hour BH4 loading test misses BH4-responsive PKU patients. Secondary, we assessed if it would be beneficial to 1) use a cut-off value of 20% Phe reduction instead of commonly used 30%, and 2) extend the loading test to 7 days.METHODS: 24 patients with a 20-30% decrease of blood Phe levels during their initial 48-hour BH4 loading test or at least one mutation associated with long-term BH4 responsiveness, were invited to participate. 22 of them underwent the 7-day BH4 loading test. During the BH4 loading test, BH4 was administered orally once daily for 7 days (20 mg/kg/day). Blood samples on filter paper were collected at 13 time points. Potential BH4 responders (≥20% decrease in blood Phe concentrations at ≥1 moment within the first 48 h or ≥30% at ≥1 moment during the entire test) underwent a treatment trial to assess true long-term responsiveness (≥30% decrease of Phe levels compared to baseline and/or ≥50% increase in natural protein tolerance in accordance with the Dutch guidelines before 2017). The duration of the treatment trial varied from 2 to 18 months.RESULTS: Of the 22 patients who completed the 7-day BH4 loading test, 2 were excluded, 8 had negative tests and 12 were considered to be potential BH4 responders. Of these 12 potential BH4-responsive PKU patients, 5 turned out to be false positive, 6 true-responder and 1 was withdrawn.CONCLUSION: Even though the 48-hour BH4 loading test has proven its efficacy in the past, a full week may be necessary to detect all responders. So, if blood Phe concentrations during the 48-hour BH4 test shows a clear tendency, but not sufficient decrease, a full week (with only measurements each 24 h) could be offered. A threshold of ≥20% decrease within 48 h is not useful for predicting true BH4 responsiveness.

AB - BACKGROUND: Phenylketonuria (PKU) is an inborn error of phenylalanine (Phe) metabolism. Besides dietary treatment, some patients are responsive to and treated with tetrahydrobiopterin (BH4). Our primary objective was to examine whether the 48-hour BH4 loading test misses BH4-responsive PKU patients. Secondary, we assessed if it would be beneficial to 1) use a cut-off value of 20% Phe reduction instead of commonly used 30%, and 2) extend the loading test to 7 days.METHODS: 24 patients with a 20-30% decrease of blood Phe levels during their initial 48-hour BH4 loading test or at least one mutation associated with long-term BH4 responsiveness, were invited to participate. 22 of them underwent the 7-day BH4 loading test. During the BH4 loading test, BH4 was administered orally once daily for 7 days (20 mg/kg/day). Blood samples on filter paper were collected at 13 time points. Potential BH4 responders (≥20% decrease in blood Phe concentrations at ≥1 moment within the first 48 h or ≥30% at ≥1 moment during the entire test) underwent a treatment trial to assess true long-term responsiveness (≥30% decrease of Phe levels compared to baseline and/or ≥50% increase in natural protein tolerance in accordance with the Dutch guidelines before 2017). The duration of the treatment trial varied from 2 to 18 months.RESULTS: Of the 22 patients who completed the 7-day BH4 loading test, 2 were excluded, 8 had negative tests and 12 were considered to be potential BH4 responders. Of these 12 potential BH4-responsive PKU patients, 5 turned out to be false positive, 6 true-responder and 1 was withdrawn.CONCLUSION: Even though the 48-hour BH4 loading test has proven its efficacy in the past, a full week may be necessary to detect all responders. So, if blood Phe concentrations during the 48-hour BH4 test shows a clear tendency, but not sufficient decrease, a full week (with only measurements each 24 h) could be offered. A threshold of ≥20% decrease within 48 h is not useful for predicting true BH4 responsiveness.

U2 - 10.1016/j.ymgme.2019.12.011

DO - 10.1016/j.ymgme.2019.12.011

M3 - Article

C2 - 31924462

VL - 129

SP - 186

EP - 192

JO - Molecular Genetics and Metabolism

JF - Molecular Genetics and Metabolism

SN - 1096-7192

IS - 3

ER -

ID: 121186875