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Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2015

Open Access 01-12-2015 | Research

Long-term follow-up of patients with phenylketonuria treated with tetrahydrobiopterin: a seven years experience

Authors: Iris Scala, Daniela Concolino, Roberto Della Casa, Anna Nastasi, Carla Ungaro, Serena Paladino, Brunella Capaldo, Margherita Ruoppolo, Aurora Daniele, Giuseppe Bonapace, Pietro Strisciuglio, Giancarlo Parenti, Generoso Andria

Published in: Orphanet Journal of Rare Diseases | Issue 1/2015

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Abstract

Background

Phenylketonuria (PKU) is an autosomal recessive disorder caused by the deficiency of phenylalanine hydroxylase that catalyzes the conversion of phenylalanine to tyrosine, using tetrahydrobiopterin (BH4) as coenzyme. Besides dietary phenylalanine restriction, new therapeutic options are emerging, such as the treatment with BH4 in subgroups of PKU patients responding to a loading test with BH4.

Methods

A no-profit open-label interventional trial with long-term oral BH4 therapy, sponsored by the Italian Medicines Agency (AIFA), was performed in a group of 17 PKU patients resulted as BH4 responders among 46 subjects analyzed for BH4-responsiveness (prot. FARM5MATC7). We report on efficacy and safety data of BH4 therapy and analyze factors predicting BH4-responsiveness and long-term response to BH4. A BH4-withdrawal test was used as a proof of the efficacy of long-term therapy with BH4.

Results

Forty-four percent of the patients responded to the 48 h-long loading test with BH4. All the phenotypic classes were represented. Genotype was the best predictor of responsiveness, along with lower phenylalanine levels at diagnosis, higher tolerance and lower phenylalanine/tyrosine ratio before the test. In BH4 responder patients, long-term BH4 therapy resulted safe and effective in increasing tolerance while maintaining a good metabolic control. The BH4 withdrawal test, performed in a subset of patients, showed that improved tolerance was directly dependent on BH4 assumption. Tolerance to phenylalanine was re-evaluated in 43.5% of patients and was longitudinally analyzed in 5 patients.

Conclusions

Long-term treatment with BH4 is safe and effective in increasing tolerance to phenylalanine. There is real need to assess the actual tolerance to phenylalanine in PKU patients to ameliorate quality of life, improve nutritional status, avoiding unnecessarily restricted diets, and interpret the effects of new therapies for PKU.
Appendix
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Metadata
Title
Long-term follow-up of patients with phenylketonuria treated with tetrahydrobiopterin: a seven years experience
Authors
Iris Scala
Daniela Concolino
Roberto Della Casa
Anna Nastasi
Carla Ungaro
Serena Paladino
Brunella Capaldo
Margherita Ruoppolo
Aurora Daniele
Giuseppe Bonapace
Pietro Strisciuglio
Giancarlo Parenti
Generoso Andria
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2015
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/s13023-015-0227-8

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