The first European guidelines on phenylketonuria: Usefulness and implications for BH4 responsiveness testing

Roeland A. F. Evers; Annemiek M. J. van Wegberg; Karen Anjema; Charlotte M. A. Lubout; Esther van Dam; Danique van Vliet; Nenad Blau; Francjan J. van Spronsen

doi:10.1002/jimd.12173

journal article Nov 20, 2019

The first European guidelines on phenylketonuria: Usefulness and implications for BH4 responsiveness testing

Roeland A. F. Evers Annemiek M. J. van Wegberg Karen Anjema Charlotte M. A. Lubout Esther van Dam Danique van Vliet Nenad Blau Francjan J. van Spronsen

Journal of Inherited Metabolic Disease Vol. 43 No. 2 pp. 244-250 · Wiley

View at Publisher Save 10.1002/jimd.12173

Abstract

AbstractObjectiveThis study aimed to investigate and improve the usefulness of the 48‐hour BH4 loading test and to assess genotype for BH4 responsiveness prediction, using the new definition of BH4 responsiveness from the European guidelines, as well as an amended definition.MethodApplying the definition of the European guidelines (≥100% increase in natural protein tolerance) and an amended definition (≥100% increase in natural protein tolerance or tolerating a safe natural protein intake) to a previous dataset, we first assessed the positive predictive value (PPV) of the 48‐hour BH4 loading test using a cutoff value of 30%. Then, we tried to improve this PPV by using different cutoff values and separate time points. Last, using the BIOPKU database, we compared predicted BH4 responsiveness (according to genotype) and genotypic phenotype values (GPVs) in BH4‐responsive and BH4‐unresponsive patients.ResultsThe PPV of the 48‐hour loading test was 50.0% using the definition of the European guidelines, and 69.4% when applying the amended definition of BH4 responsiveness. Higher cutoff values led to a higher PPV, but resulted in an increase in false‐negative tests. Parameters for genotype overlapped between BH4‐responsive and BH4‐unresponsive patients, although BH4 responsiveness was not observed in patients with a GPV below 2.4.ConclusionThe 48‐hour BH4 loading test is not as useful as previously considered and cannot be improved easily, whereas genotype seems mainly helpful in excluding BH4 responsiveness. Overall, the definition of BH4 responsiveness and BH4 responsiveness testing require further attention.

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Cited By

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Phenylketonuria

Francjan J. van Spronsen, Nenad Blau · 2021

Nature Reviews Disease Primers

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13

Citations

16

References

Details

Published: Nov 20, 2019
Vol/Issue: 43(2)
Pages: 244-250
License: View

Authors

R

Roeland A. F. Evers