The neonatal tetrahydrobiopterin loading test in phenylketonuria: what is the predictive value?

Contains fulltext : 171759.pdf (publisher's version ) (Open Access)BACKGROUND: It is unknown whether the neonatal tetrahydrobiopterin (BH4) loading test is adequate to diagnose long-term BH4 responsiveness in PKU. Therefore we compared the predictive value of the neonatal (test I) versus the 48-h BH4 loading test (test II) and long-term BH4 responsiveness. METHODS: Data on test I (>1991, 20 mg/kg) at T = 8 (n = 85) and T = 24 (n = 5) were collected and compared with test II and long-term BH4 responsiveness at later age, with >/=30 % Phe decrease used as the cut-off. RESULTS: The median (IQR) age at hospital diagnosis was 9 (7-11) days and the age at test II was 11.8 (6.6-13.7) years. The baseline Phe concentrations at test I were significantly higher compared to test II (1309 (834-1710) versus 514 (402-689) mumol/L, respectively, P = 0.000). 15/85 patients had a positive test I T = 8. All, except one patient who was not tested for long-term BH4 responsiveness, showed long-term BH4 responsiveness. In 20/70 patients with a negative test I T = 8, long-term BH4 responsiveness was confirmed. Of 5 patients with a test I T = 24, 1/5 was positive at both tests and showed long-term BH4 responsiveness, 2/5 had negative results at both tests and 2/5 showed a negative test I T = 24, but a positive test II with 1/2 showing long-term BH4 responsiveness. CONCLUSIONS: Both a positive neonatal 8- and 24-h BH4 loading test are predictive for long-term BH4 responsiveness. However, a negative test does not rule out long-term BH4 responsiveness. Other alternatives to test for BH4 responsiveness at neonatal age should be investigated

Follow-up and outcome of PKU patients on sapropterin/BH4 : Preliminary results of a retrospective European Multicenter Study

Background: Sapropterin/BH4 is an approved drug for treatment of responsive PKU patients. The purpose of this study was to collect data on the use of Sapropterin/BH4 and its long-term effect on metabolic control and patient-related outcome in five European countries. Methods: A questionnaire was developed to assess quality of life (QOL), mood changes, adherence to diet, changes in blood Phe levels and Phe tolerance and patients' phenotype and genotype. Results: 129 patients from 11 European centers (42,5% MHP, 49,6 mild PKU, 7,9% classical PKU) were accessed (62 male, 67 female, age 2-46 years). No adverse events on Sapropterin/BH4 were reported. Average dose of Sapropterin/BH4 was 10,45 mg/kg/day; range 5,15. Improvement in QOL was reported qualitively in 52,3% (31,3% did not report); improvement in adherence to diet in 52,3% (in 17,2% question not applicable); improvement in mood was reported in 14,1% (in 41,4% question not applicable) of patients. Conclusion: Our data suggest a beneficial effect of sapropterin/BH4 in PKU patients who respond to oral administration of BH4 by lowering their blood Phe levels by > 30%; it increases daily tolerance for dietary Phe intake and improves dietary adherence and QOL. Conflict of Interest declared

The 48-hour tetrahydrobiopterin loading test in patients with phenylketonuria: evaluation of protocol and influence of baseline phenylalanine concentration.

Item does not contain fulltextBACKGROUND: The 24- and 48-hour tetrahydrobiopterin (BH4) loading test (BLT) performed at a minimum baseline phenylalanine concentration of 400 mumol/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 400 mumol/l minimum baseline phenylalanine concentration. METHODS: Data on 186 phenylketonuria patients were collected. Patients were supplemented with phenylalanine if phenylalanine was /= 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 <400 mumol/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 <400 mumol/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