title: Key European guidelines for the diagnosis and management of patients with phenylketonuria.
abstract: We developed European guidelines to optimise phenylketonuria (PKU) care. To develop the guidelines, we did a literature search, critical appraisal, and evidence grading according to the Scottish Intercollegiate Guidelines Network method. We used the Delphi method when little or no evidence was available. From the 70 recommendations formulated, in this Review we describe ten that we deem as having the highest priority. Diet is the cornerstone of treatment, although some patients can benefit from tetrahydrobiopterin (BH4). Untreated blood phenylalanine concentrations determine management of people with PKU. No intervention is required if the blood phenylalanine concentration is less than 360 μmol/L. Treatment is recommended up to the age of 12 years if the phenylalanine blood concentration is between 360 μmol/L and 600 μmol/L, and lifelong treatment is recommended if the concentration is more than 600 μmol/L. For women trying to conceive and during pregnancy (maternal PKU), untreated phenylalanine blood concentrations of more than 360 μmol/L need to be reduced. Treatment target concentrations are as follows: 120-360 μmol/L for individuals aged 0-12 years and for maternal PKU, and 120-600 μmol/L for non-pregnant individuals older than 12 years. Minimum requirements for the management and follow-up of patients with PKU are scheduled according to age, adherence to treatment, and clinical status. Nutritional, clinical, and biochemical follow-up is necessary for all patients, regardless of therapy.
authors.affiliation: Division of Metabolic Diseases, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, Netherlands. Electronic address: f.j.van.spronsen@umcg.nl.
authors.forename: Francjan J
authors.initials: FJ
authors.lastname: van Spronsen
authors.affiliation: Division of Metabolic Diseases, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
authors.forename: Annemiek Mj
authors.initials: AM
authors.lastname: van Wegberg
authors.affiliation: Department of PKU, Kennedy Centre, Copenhagen University Hospital, Glostrup, Denmark.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Ahring
authors.affiliation: Metabolic Diseases Unit, Department of Pediatrics, Hospital Ramon y Cajal, Madrid, Spain.
authors.forename: Amaya
authors.initials: A
authors.lastname: Bélanger-Quintana
authors.affiliation: University Children's Hospital, Dietmar-Hoppe Metabolic Centre, Heidelberg, Germany; University Children's Hospital Zurich, Zurich, Switzerland.
authors.forename: Nenad
authors.initials: N
authors.lastname: Blau
authors.affiliation: Department of Paediatrics, Division of Metabolic Disorders, Academic Medical Centre, University Hospital of Amsterdam, Amsterdam, Netherlands.
authors.forename: Annet M
authors.initials: AM
authors.lastname: Bosch
authors.affiliation: Division of Inherited Metabolic Diseases, Department of Paediatrics, University Hospital of Padova, Padova, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Burlina
authors.affiliation: Neuropaediatrics Department, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.
authors.forename: Jaime
authors.initials: J
authors.lastname: Campistol
authors.affiliation: Department of Pediatrics, Hôpital d'Enfants Brabois, CHU Nancy, Vandoeuvre les Nancy, France.
authors.forename: Francois
authors.initials: F
authors.lastname: Feillet
authors.affiliation: Department of Pediatrics, Endocrinology, Diabetology, Metabolic Diseases and Cardiology of the Developmental Age, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Giżewska
authors.affiliation: Department of Clinical Child and Adolescent Studies-Neurodevelopmental Disorders, Faculty of Social Sciences, Leiden University, Leiden, Netherlands.
authors.forename: Stephan C
authors.initials: SC
authors.lastname: Huijbregts
authors.affiliation: Clinical Psychology Department, Birmingham Children's Hospital, Birmingham, UK.
authors.forename: Shauna
authors.initials: S
authors.lastname: Kearney
authors.affiliation: Department of Pediatrics, Child Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Leuzzi
authors.affiliation: Internal Medicine Service, CHRU de Tours, François Rabelais University, Tours, France.
authors.forename: Francois
authors.initials: F
authors.lastname: Maillot
authors.affiliation: University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Ania C
authors.initials: AC
authors.lastname: Muntau
authors.affiliation: University Children's Hospital, Dietmar-Hoppe Metabolic Centre, Heidelberg, Germany.
authors.forename: Fritz K
authors.initials: FK
authors.lastname: Trefz
authors.affiliation: Department of Dietetics, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
authors.forename: Margreet
authors.initials: M
authors.lastname: van Rijn
authors.affiliation: Manchester Academic Health Sciences Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
authors.forename: John H
authors.initials: JH
authors.lastname: Walter
authors.affiliation: Dietetic Department, Birmingham Children's Hospital, Birmingham, UK.
authors.forename: Anita
authors.initials: A
authors.lastname: MacDonald
mesh_terms: D001708:Biopterins / Q000008:administration & dosage / Q000031:analogs & derivatives; D003697:Delphi Technique; D019468:Disease Management; D005060:Europe; D006801:Humans; D010649:Phenylalanine / Q000097:blood; D010661:Phenylketonurias / Q000097:blood / Q000175:diagnosis* / Q000178:diet therapy*
chemical_list: D001708:Biopterins; D010649:Phenylalanine; C003402:sapropterin