NDLI: Tetrahydrobiopterin responsiveness in phenylketonuria: prediction with the 48-hour loading test and genotype

Content Provider	Springer Nature : BioMed Central
Author	Anjema, Karen van Rijn, Margreet Hofstede, Floris C Bosch, Annet M Hollak, Carla EM Rubio-Gozalbo, Estela de Vries, Maaike C Janssen, Mirian CH Boelen, Carolien CA Burgerhof, Johannes GM Blau, Nenad Heiner-Fokkema, M Rebecca van Spronsen, Francjan J
Abstract	Background How to efficiently diagnose tetrahydrobiopterin (BH4) responsiveness in patients with phenylketonuria remains unclear. This study investigated the positive predictive value (PPV) of the 48-hour BH4 loading test and the additional value of genotype. Methods Data of the 48-hour BH4 loading test (20 mg BH4/kg/day) were collected at six Dutch university hospitals. Patients with ≥30% phenylalanine reduction at ≥1 time points during the 48 hours (potential responders) were invited for the BH4 extension phase, designed to establish true-positive BH4 responsiveness. This is defined as long-term ≥30% reduction in mean phenylalanine concentration and/or ≥4 g/day and/or ≥50% increase of natural protein intake. Genotype was collected if available. Results 177/183 patients successfully completed the 48-hour BH4 loading test. 80/177 were potential responders and 67/80 completed the BH4 extension phase. In 58/67 true-positive BH4 responsiveness was confirmed (PPV 87%). The genotype was available for 120/177 patients. 41/44 patients with ≥1 mutation associated with long-term BH4 responsiveness showed potential BH4 responsiveness in the 48-hour test and 34/41 completed the BH4 extension phase. In 33/34 true-positive BH4 responsiveness was confirmed. 4/40 patients with two known putative null mutations were potential responders; 2/4 performed the BH4 extension phase but showed no true-positive BH4 responsiveness. Conclusions The 48-hour BH4 loading test in combination with a classified genotype is a good parameter in predicting true-positive BH4 responsiveness. We propose assessing genotype first, particularly in the neonatal period. Patients with two known putative null mutations can be excluded from BH4 testing.
Related Links	https://ojrd.biomedcentral.com/counter/pdf/10.1186/1750-1172-8-103.pdf
Ending Page	9
Page Count	9
Starting Page	1
File Format	HTM / HTML
ISSN	17501172
DOI	10.1186/1750-1172-8-103
Journal	Orphanet Journal of Rare Diseases
Issue Number	1
Volume Number	8
Language	English
Publisher	BioMed Central
Publisher Date	2013-07-10
Access Restriction	Open
Subject Keyword	Medicine Public Health Pharmacology Toxicology Human Genetics Phenylketonuria PKU Tetrahydrobiopterin Sapropterin dihydrochloride Pharmacological chaperone Genotype Loading test Medicine/Public Health Pharmacology/Toxicology
Content Type	Text
Resource Type	Article
Subject	Pharmacology (medical) Genetics (clinical)
Journal Impact Factor	3.4/2023
5-Year Journal Impact Factor	3.9/2023

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Tetrahydrobiopterin responsiveness in phenylketonuria: prediction with the 48-hour loading test and genotype

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