Search

Abstract: Background: The 24- and 48-hour tetrahydrobiopterin (BH4) loading test (BLT) performed at a minimum baseline phenylalanine concentration of 400μmol/l is commonly used to test phenylketonuria patients for BH4 responsiveness. This study aimed to analyze differences between the 24- and 48-hour BLT and the necessity of the 400μmol/l minimum baseline phenylalanine concentration. Methods: Data on 186 phenylketonuria patients were collected. Patients were supplemented with phenylalanine if phenylalanine was <400μmol/l. BH4 20mg/kg was administered at T=0 and T=24. Blood samples were taken at T=0, 8, 16, 24 and 48h. Responsiveness was defined as ≥30% reduction in phenylalanine concentration at ≥1 time point. Results: Eighty-six (46.2%) patients were responsive. Among responders 84% showed a ≥30% response at T=48. Fifty-three percent had their maximal decrease at T=48. Fourteen patients had ≥30% phenylalanine decrease not before T=48. A ≥30% decrease was also seen in patients with phenylalanine concentrations <400μmol/l. Conclusion: In the 48-hour BLT, T=48 seems more informative than T=24. Sampling at T=32, and T=40 may have additional value. BH4 responsiveness can also be predicted with baseline blood phenylalanine <400μmol/l, when the BLT is positive. Therefore, if these results are confirmed by data on long-term BH4 responsiveness, we advise to first perform a BLT without phenylalanine loading and re-test at higher phenylalanine concentrations when no response is seen. Most likely, the 48-hour BLT is a good indicator for BH4 responsiveness, but comparison with long term responsiveness is necessary. [Copyright &y& Elsevier]