European guidelines on diagnosis and treatment of phenylketonuria: First revision
- PMID: 40378670
- DOI: 10.1016/j.ymgme.2025.109125
European guidelines on diagnosis and treatment of phenylketonuria: First revision
Abstract
Phenylketonuria (PKU) is an autosomal recessive inherited disorder of phenylalanine metabolism caused by deficiency of the enzyme phenylalanine hydroxylase that converts phenylalanine into tyrosine. Untreated, PKU results in elevated phenylalanine levels in blood and brain, which cause severe intellectual disability, epilepsy and behavioural problems. For this first revision of the European PKU Guidelines previous recommendations were re-evaluated and updated according to new research findings. Twenty-one professionals were divided across four working groups and supported by a coordinator and chair. In addition to an update of the previous 70 recommendations, 20 new topics were included, resulting in a total of 87 statements in this first revision of the guidelines. Research publications were reviewed up until September 2022. Evidence was graded as high, moderate, low, very low or expert opinion and the recommendations were graded conditional or strong according to GRADE methodology. All recommendations were discussed during 14 plenary online or in person meetings. Recommendations were accepted if more than 75 % of the professionals were in agreement. When recommendations were not amended, the text reported in the European guidelines of 2017 remains valid.
Keywords: PKU; Recommendations.
Copyright © 2025. Published by Elsevier Inc.
Conflict of interest statement
Declaration of competing interest The UMCG as employer of A.v.W. has received a research grant from Nutricia, and speakers honoraria and advisory board fees from Nutricia, Vitaflo and PTC Therapeutics. A.M. received research funding, speakers honoraria and advisory board fees from Nutricia, Vitaflo International, Biomarin, Nutricia, PTC Therapeutics, Applied Pharma Research, Arla Food Ingredients, Meta Health, Galen, Metax, PIAM, Jnana Therapeutics, and Cambrookes. N.B. received consulting fees from PTC Therapeutics, AlltRNA, Jnana Therapeutics, Merck, Nestle, and EntacBio. S.B. received investigator initiated research funds from Nutricia metabolics as well as speakers honoraria and advisory board fees from Nutricia Metabolics, MetaX, Biomarin, Immedica and Sanofi. J.C. has received a research honoraria as a speaker from Nutricia, Merck Serono, Biomarin, Rendon Europa and PTC Therapeutics. M.G. received financial support and honoraria as a speaker from Biomarin, Nutricia, Vitaflo, Nestlé Polska, Mead-Johnson, PTC Therapeutics International and APR Applied Pharma Research. F.F. has received honoraria from BioMarin, Merck Serono, Nutricia International/Danone, PTC therapeutics, Vitaflo, Jnana Therapeutics and Recordati. S.C.J. H. has participated in strategic advisory boards and received grants and honoraria as a consultant and/or speaker from BioMarin, Merck Serono SA, Homology Medicines, Nutricia and UMCG. F.M. has received honoraria as a consultant from Jnana Therapeutics and PTC Therapeutics, honoraria as a speaker from PTC therapeutics, travel support by Biomarin, TAKEDA, SANOFI and a research grant from Biomarin. C.R. has received donations from Nutricia, Vitaflo and NSPKU. J.C.R. was a member of the European Nutritionist Expert Panel (Biomarin) and the Advisory Board for Applied Pharma Research, Vitaflo, Synlogic, Biomarin, Nutricia, Moderna and PTC Therapeutics and received honoraria as a speaker from APR, Merck Serono, Biomarin, Nutricia, Vitaflo, Cambrooke, PIAM, Lifediet and PTC Therapeutics. The UMCG as employer of FvS has received research grants, advisory board fees, and/or speaker's honoraria from Agios, Alexion, AlltRNA, Applied Pharma Research, Arla Food Int., Biomarin, Beatrix Research Fund, ESPKU, Nestle-Codexis Alliance, Moderna, Nutricia, NPKUA, NPKUV, Pluvia Biotech, PTC Therapeutics, Rivium Medical BV, Sobi, Tyrosinemia Foundation, Vitaflo, and ZONMW. The other authors (A.Bo., A.Bu., K.A., T.C., V.L. F.T.) declare no competing of interest.