Advances of Phenylketonuria in Children

A special issue of Children (ISSN 2227-9067). This special issue belongs to the section "Pediatric Endocrinology & Diabetes".

Deadline for manuscript submissions: 1 August 2025 | Viewed by 652

Special Issue Editors


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Guest Editor
Department of Pediatrics, School of Medicine, UPMC Children’s Hospital of Pittsburgh, 4401 Penn Ave., Pittsburgh, PA 15224, USA
Interests: health-related quality of life; adherence to treatment; cognition; behavior; attention problems; mutation analysis; haplotyping; genotype–phenotype correlations in phenylketonuria and other inherited metabolic disorders

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Guest Editor
Institute of Childcare and Pediatrics Martagão Gesteira/UFRJ, Federal University of Rio de Janeiro, Rio de Janeiro 21941-912, RJ, Brazil
Interests: pediatrics; biological sciences; genetics; genotype–phenotype correlations in phenylketonuria

Special Issue Information

Dear Colleagues,

In 1934, when Dr. Følling detected phenylpyruvic acid in the urine of two siblings with severe intellectual disability in Norway, the association between a metabolic disorder and intellectual disability was established for the first time in the history of medicine. In 1946, the English geneticist Lionel Penrose would name the disease discovered by Dr. Følling phenylketonuria (PKU). In the 1950s, Horst Bickel, at Birmingham Children's University Hospital, UK, laid the foundations for the use of phenylalanine-free amino acid formulas as the mainstay of PKU treatment. In 1963, Dr. Guthrie, in the U.S.A. developed a method for measuring phenylalanine from dried blood spots of newborns; this enabled the establishment of population-scale PKU neonatal screening programs. However, important drawbacks remain in the management of PKU. Adherence to dietary therapy, especially after the first decade of life, is often unsatisfactory, with consequences for neurocognitive function. Behavioral and emotional problems are still described in many continuously treated children and adolescents. The neuropathology of PKU remains a major knowledge gap. Sapropterin, an oral form of tetrahydrobiopterin, is an alternative pharmacological treatment for a subset of patients with PKU, mainly those with mild or moderate metabolic phenotypes. It is not known whether pegylated phenylalanine ammonia lyase, which requires daily subcutaneous injections, is safe and effective in children. Considering this scenario, we invite our colleagues to contribute reviews and original articles to this Special Issue investigating the quality of life, behavioral and emotional problems, adherence to dietary treatment, neuropathology, and pharmacological therapies of PKU in children, including preclinical (in vitro and animal models) and clinical studies.

Dr. Eduardo Vieira Neto
Prof. Dr. Márcia Gonçalves Ribeiro
Guest Editors

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Keywords

  • phenylketonuria
  • hyperphenylalaninemia
  • quality of life
  • patient compliance
  • diet therapy
  • child behavior
  • cognition
  • attention
  • executive function
  • tetrahydrobiopterin
  • brain
  • white matter abnormalities

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Published Papers (1 paper)

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Research

10 pages, 897 KiB  
Article
The Influence of Phenylalanine Fluctuations and Intake on a 24 h Sapropterin Responsiveness Test in Patients with Phenylketonuria
by Ana Jaqueline Nunes, Bianca Fasolo Franceschetto, Lisiane da Gama, Soraia Poloni, Lilia Farret Refosco, Tassia Tonon, Vaneisse Monteiro, Rafael Hencke Tresbach, Fernanda Sperb-Ludwig, François Maillot and Ida Vanessa Doederlein Schwartz
Children 2025, 12(5), 541; https://doi.org/10.3390/children12050541 - 24 Apr 2025
Viewed by 216
Abstract
Patients with phenylketonuria (PKU) who retain residual phenylalanine hydroxylase (PAH) activity may benefit from sapropterin dihydrochloride (sapropterin) administration. Objective: To characterize sapropterin responsiveness in patients with PKU and investigate the impact of natural fluctuations in phenylalanine (PHE) levels and variations in PHE intake [...] Read more.
Patients with phenylketonuria (PKU) who retain residual phenylalanine hydroxylase (PAH) activity may benefit from sapropterin dihydrochloride (sapropterin) administration. Objective: To characterize sapropterin responsiveness in patients with PKU and investigate the impact of natural fluctuations in phenylalanine (PHE) levels and variations in PHE intake on sapropterin responsiveness. Methods: Retrospective chart review study. Patients with PKU who underwent the 24 h responsiveness test, including correction for natural PHE fluctuations, were included. Responders were defined as those who exhibited a >30% reduction in PHE levels within 8 h and/or 24 h after intake of 20 mg/kg sapropterin, correcting for the natural fluctuation in plasma PHE levels on day 1. Patients with a 28–30% reduction in PHE were considered sapropterin-responsive only if they had a concordant genotype. Results: Fifteen patients completed the test; however, three were excluded due to non-compliance. Additionally, one patient with mild PKU exhibited a borderline response, but the genotype agreement could not be assessed, rendering the test inconclusive. The rate of responsiveness could be assessed for eleven patients (six mild and five classical PKU). Among the patients with mild PKU, four were classified as responders: three at both 8 h and 24 h (reduction in plasma PHE: −75.9 ± 20.2% at 8 h and −75.7 ± 37.0% at 24 h) and one at 8 h only (reduction in plasma PHE: −28.7%). All patients with classic PKU (n = 5) were non-responders. Conclusions: A 24 h sapropterin responsiveness test incorporating correction for natural fluctuations in PHE levels identified a proportion of sapropterin-responsive patients with mild PKU similar to that described in the literature. PHE consumption should be objectively controlled during the protocol to avoid bias in determining responsiveness. Full article
(This article belongs to the Special Issue Advances of Phenylketonuria in Children)
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