Trial reportOrphanet journal of rare diseases2015
Long-term follow-up of patients with phenylketonuria treated with tetrahydrobiopterin: a seven years experience.
Trial report in Orphanet journal of rare diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Dietary Liberalization in Tetrahydrobiopterin-Treated PKU Patients: Does It Improve Outcomes?Nutrients · 2022Pooled it
- Protein Substitute Requirements of Patients with Phenylketonuria on BH4 Treatment: A Systematic Review and Meta-Analysis.Nutrients · 2021Pooled it
- Molecular Genetic and Biochemical Characterization of Hyperphenylalaninemia Based on Expanded Neonatal Screening Data from 2023 to 2024 in the Russian Federation.International journal of molecular sciences · 2026Article
- Inborn Errors of Amino Acid Metabolism Revisited: Clinical Implications and Insights into Current Therapies.Journal of clinical medicine · 2025Review
- Improving sapropterin administration efficacy in PKU: Clinical practice case studies.Molecular genetics and metabolism reports · 2025Article
- Sapropterin Dihydrochloride Responsiveness in Phenylketonuria: A Case Series Exploring Gaps in Comprehensive Patient Monitoring.Nutrients · 2025Article
- Blood phenylalanine lowering partially reverses white matter changes in a mouse model of phenylketonuria.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Blood Phenylalanine Levels in Patients with Phenylketonuria from Europe between 2012 and 2018: Is It a Changing Landscape?Nutrients · 2024Article
- Expert Consensus on the Long-Term Effectiveness of Medical Nutrition Therapy and Its Impact on the Outcomes of Adults with Phenylketonuria.Nutrients · 2023Article
- Blood phenylalanine reduction reverses gene expression changes observed in a mouse model of phenylketonuria.Scientific reports · 2021Article
- Beneficial Effects of Slow-Release Large Neutral Amino Acids after a Phenylalanine Oral Load in Patients with Phenylketonuria.Nutrients · 2021Article
- Development of a mutation hotspot detection kit for the phenylalanine hydroxylase gene by ARMS-PCR combined with fluorescent probe technology.Bioscience reports · 2021Article
- Article
- Neonatal phenylalanine wash-out in phenylketonuria.Metabolic brain disease · 2020Article
- Large Neutral Amino Acids (LNAAs) Supplementation Improves Neuropsychological Performances in Adult Patients with Phenylketonuria.Nutrients · 2020Article
- Structural and Functional Impact of Seven Missense Variants of Phenylalanine Hydroxylase.Genes · 2019Article
- Genotype-phenotype correlations and BHMolecular genetics & genomic medicine · 2019Article
- l-Phenylalanine Restores Vascular Function in Spontaneously Hypertensive Rats Through Activation of the GCH1-GFRP Complex.JACC. Basic to translational science · 2018Article
- Extended Experience of Lower Dose Sapropterin in Irish Adults with Mild Phenylketonuria.JIMD reports · 2018Article
- When Is a Rare Disease Not so Rare? Implications for Medical Nutrition Therapy.Integrative medicine (Encinitas, Calif.) · 2016Article
Corrections and comments
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPhenylketonuria (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.
methodsA 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.
resultsForty-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.
conclusionsLong-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.
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