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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-56815

Nalin, T; Perry, I D; Sitta, A; Vargas, C R; Saraiva-Pereira, M L; Giugliani, R; Blau, N; Schwartz, I V (2011). Optimized loading test to evaluate responsiveness to tetrahydrobiopterin (BH4) in Brazilian patients with phenylalanine hydroxylase deficiency. Molecular Genetics and Metabolism, 104(Suppl.):S80-S85.

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Recent studies showed that phenylalanine (Phe) plasma concentrations may decrease in some patients with hyperphenylalaninemia (HPA) due to phenylalanine hydroxylase (PAH) deficiency, after the administration of tetrahydrobiopterin (BH(4)).

To determine responsiveness to a single dose of BH(4) administered according to an innovative protocol using a combined Phe and BH(4) loading test in Brazilian phenylketonuria (PKU) patients.

Patient age should be ≥ 4 years, and median Phe plasma concentration ≤ 600 μmol/L when following dietary restrictions. Participants received a simple Phe loading test using 100mg/kg L-Phe (Test 1) and a combined Phe+BH(4) loading test using 100mg/kg L-Phe and 20mg/kg/BH(4) (Test 2). Blood samples were collected at baseline and 3, 11 and 27 h after Phe ingestion (T0, T1, T2 and T3). Responsiveness was defined as: criterion A: plasma Phe reduction of ≥ 30% at T1 and T2 for Tests 1 and 2; criterion B: plasma Phe reduction of ≥ 30% at T1 and T3 for Tests 1 and 2; and criterion C: at least 30% difference of the areas under the Phe curve for Tests 1 and 2.

Eighteen patients (median age 12 yrs; 8 classical PKU; 10 mild PKU) participated in the study. Six patients (2 classical PKU; 4 mild PKU) were classified as responsive according to at least one of the criteria. Responsiveness was concordant when criteria A + B we compared with criterion C (kappa = 0.557; p = 0.017). Of the patients whose genotype was available (n = 16), six had data about BH(4)-responsiveness genotypes described in the literature, which were in agreement with our findings.

The comparison of simple Phe loading and combined Phe + BH(4) loading seems to be an optimal method to evaluate responsiveness to BH(4) in patients with good metabolic control.

Copyright © 2011 Elsevier Inc. All rights reserved.


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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
04 Faculty of Medicine > Center for Integrative Human Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Deposited On:28 Jan 2012 16:04
Last Modified:05 Apr 2016 15:28
Publisher DOI:10.1016/j.ymgme.2011.09.019
PubMed ID:22014474

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