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

• Published in: Molecular genetics and metabolism Vol. 104; pp. S60 - S63
• Main Authors: Anjema, K., Venema, G., Hofstede, F.C., Carbasius Weber, E.C., Bosch, A.M., Ter Horst, N.M., Hollak, C.E.M., Jonkers, C.F., Rubio–Gozalbo, M.E., van der Ploeg, E.M.C., de Vries, M.C., Janssen-Regelink, R.G., Janssen, M.C.H., Zweers-van Essen, H., Boelen, C.C.A., van der Herberg-van de Wetering, N.A.P., Heiner-Fokkema, M.R., van Rijn, M., van Spronsen, F.J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 2011
• Subjects: Adolescent; Adult; BH4; Biopterins - analogs & derivatives; Biopterins - therapeutic use; Child; Child, Preschool; Demography; Diagnostic Techniques and Procedures; Female; Humans; Infant; Male; Middle Aged; Phenylalanine; Phenylalanine - blood; Phenylketonuria; Phenylketonurias - blood; Phenylketonurias - drug therapy; PKU; Sapropterin; Tetrahydrobiopterin; Time Factors; Sapropterin; Phenylketonuria; Phenylalanine; Tetrahydrobiopterin; PAH; BLT; PKU; Phe; BH4
• ISSN: 1096-7192; 1096-7206
• DOI: 10.1016/j.ymgme.2011.09.024

The 24- and 48-hour tetrahydrobiopterin (BH4) loading test (BLT) performed at a minimum baseline phenylalanine concentration of 400
μmol/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
μmol/l minimum baseline phenylalanine concentration.
Data on 186 phenylketonuria patients were collected. Patients were supplemented with phenylalanine if phenylalanine was <
400
μmol/l. BH4 20
mg/kg was administered at T
=
0 and T
=
24. Blood samples were taken at T
=
0, 8, 16, 24 and 48
h. Responsiveness was defined as ≥
30% reduction in phenylalanine concentration at ≥
1 time point.
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
μmol/l.
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
μmol/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.