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

Orphanet Journal of Rare Diseases
Iris ScalaGeneroso Andria

Abstract

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. 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. 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 resul...Continue Reading

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Citations

Sep 11, 2019·Journal of Inherited Metabolic Disease·Roeland A F EversFrancjan J van Spronsen
Feb 26, 2016·Journal of Pediatric Endocrinology & Metabolism : JPEM·Mojca Zerjav TansekTadej Battelino
Jul 15, 2020·Metabolic Brain Disease·Francesco PortaMarco Spada
Jun 27, 2019·Journal of Pediatric Endocrinology & Metabolism : JPEM·Peyman EshraghiVajiheh Chalak
Mar 7, 2021·Nutrients·Ella NewbouldAnita MacDonald

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Methods Mentioned

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