Tetrahydrobiopterin responsiveness in phenylketonuria: prediction with the 48-hour loading test and genotype.
Orphanet J Rare Dis
; 8: 103, 2013 Jul 10.
Article
em En
| MEDLINE
| ID: mdl-23842451
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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Fenilcetonúrias
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Biopterinas
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Adolescent
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Adult
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Child
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Female
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Humans
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Male
Idioma:
En
Revista:
Orphanet J Rare Dis
Assunto da revista:
MEDICINA
Ano de publicação:
2013
Tipo de documento:
Article