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6R-tetrahydrobiopterin treated PKU patients below 4 years of age: Physical outcomes, nutrition and genotype

Fecha de publicación:

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

  • Aldamiz-Echevarria, L
  • Bueno, MA
  • Couce, ML
  • Lage, S
  • Llarena, M
  • Andrade, F
  • Blasco, J
  • Alcalde, C
  • Gil, D
  • Garcia, MC
  • Gonzalez-Lamuno, D
  • Ruiz, M
  • Ruiz, MA
  • Pena-Quintana, L
  • Gonzalez, D
  • Sanchez-Valverde, F

Grupos

Abstract

Background and Aims: Phenylalanine-restricted diets have proven effective in treating phenylketonuria. However, such diets have occasionally been reported to hinder normal development. Our study aimed to assess whether treating 0-4-year-old phenylketonuric patients with 6R-tetrahydrobiopterin might prevent growth retardation later in life. Methods: We conducted a longitudinal retrospective study which examined anthropometric characteristics of phenylketonuric patients on 6R-tetrahydrobiopterin therapy (22 subjects), and compared them with a group of phenylketonuric patients on protein-restricted diets (44 subjects). Nutritional issues were also considered. We further explored possible relationships between mutations in the PAH gene, BH4 responsiveness and growth outcome. Results: No significant growth improvements were observed in either the group on 6R-tetrahydrobiopterin treatment (height Z-score: initial = -0.57 +/- 1.54; final = -0.52 +/- 1.29; BMI Z-score: initial = 0.17 +/- 1.05; final = 0.18 +/- 1.00) or the diet-only group (height Z-score: initial = -0.92 +/- 0.96; final = -0.78 +/- 1.08; BMI Z-score: initial = 0.17 +/- 0.97; final = -0.07 +/- 1.03) over the 1-year observation period. Furthermore, we found no significant differences (p > 0.05) between the two groups at any of the time points considered (0, 6 and 12 months). Patients on 6R-tetrahydrobiopterin increased their phenylalanine intake (from 49.1 [25.6-60.3] to 56.5 [39.8-68.3] mg kg(-1) day(-1)) and natural protein intake (from 1.0 [0.8-1.7] to 1.5 [1.0-1.8] g kg(-1) day(-1)), and some patients managed to adopt normal diets. Higher phenylalanine and natural protein intakes were positively correlated with better physical outcomes in the diet-only group (p < 0.05). No correlation was found between patient genotype and physical outcomes, results being similar regardless of the nutritional approach used. We did not detect any side effects due to 6R-tetrahydrobiopterin administration. Conclusions: Our study indicates that treating 0-4-year-old phenylketonuric patients with 6R-tetrahydrobiopterin is safe. However, poor developmental outcomes were observed, despite increasing the intake of natural proteins. Genotype could be a valid predictor of tetrahydrobiopterin-responsiveness, since patients who carried the same genotype responded similarly to the 6R-tetrahydrobiopterin loading test. On the other hand, harbouring 6R-tetrahydrobiopterin responsive genotypes did not predispose patients to better physical outcomes. (C) 2015 Elsevier Inc. All rights reserved.

Datos de la publicación

ISSN/ISSNe:
1096-7192, 1096-7206

MOLECULAR GENETICS AND METABOLISM  ACADEMIC PRESS INC ELSEVIER SCIENCE

Tipo:
Article
Páginas:
10-16
PubMed:
25882749
Factor de Impacto:
1,541 SCImago ℠
Cuartil:
Q1 SCImago ℠

Citas Recibidas en Web of Science: 10

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Keywords

  • Tetrahydrobiopterin; Phenylketonuria; Physical outcomes; Growth

Proyectos y Estudios Clínicos

ESTUDIO POSTAUTORIZACIÓN DE SEGURIDAD (EPAS) NO INTERVENCIONAL PARA EVALUAR LA SEGURIDAD A LARGO PLAZO DEL TRATAMIENTO CON ORFADIN EN LA TIROSINEMIA HEREDITARIA TIPO 1 (TH-1) EN LA PRÁCTICA CLÍNICA ESTÁNDAR.

Investigador Principal: ISIDRO VITORIA MIÑANA

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ESTUDIO OBSERVACIONAL, AMBISPECTIVO DE HISTORIA NATURAL EN PACIENTES CON MUCOPOLISACARIDOSIS TIPO IIIA (MPS IIIA) O SÍNDROME DE SANFILIPPO TIPO A.

Investigador Principal: ISIDRO VITORIA MIÑANA

EST-SFA-2013-01 . 2014

ESTUDIO DE RESULTADOS DE HUNTER: REGISTRO OBSERVACIONAL, INTERNACIONAL Y MULTICÉNTRICO A LARGO PLAZO DE PACIENTES CON SÍNDROME DE HUNTER (MUCOPOLISACARIDOSIS DE TIPO II, MPS II).

Investigador Principal: ISIDRO VITORIA MIÑANA

SHI-IDU-2011-01 . 2014

PROTOCOLO DEL REGISTRO DE LA ENFERMEDAD DE GAUCHER.

Investigador Principal: ISIDRO VITORIA MIÑANA

GEN-GAU-2013-01 . 2018

PROTOCOLO DE VIGILANCIA DEL E-HOD/CYSTADANE.

Investigador Principal: JAIME DALMAU SERRA

ORP-CYS-2014-01

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