Opladen, ThomasLópez-Laso, EduardoCortès-Saladelafont, ElisendaPearson, Toni S.Sivri, H. SerapYildiz, YilmazAssmann, BirgitKurian, Manju A.Leuzzi, VincenzoHeales, SimonPope, SimonPorta, FrancescoGarcía-Cazorla, AngelesHonzík, TomásPons, RoserRegal, LucGoez, HellyArtuch, RafaelHoffmann, Georg F.Horvath, GabriellaThöny, BeatScholl-Bürgi, SabineBurlina, AlbertoVerbeek, Marcel M.Mastrangelo, MarioFriedman, JenniferWassenberg, TessaJeltsch, KathrinKulhánek, JanKuseyri Hübschmann, Oya2022-07-262022-07-262020-05-26Opladen T, López-Laso E, Cortès-Saladelafont E, Pearson TS, Sivri HS, Yildiz Y, et al. Consensus guideline for the diagnosis and treatment of tetrahydrobiopterin (BH4) deficiencies. Orphanet J Rare Dis. 2020 May 26;15(1):126http://hdl.handle.net/10668/3820Background Tetrahydrobiopterin (BH4) deficiencies comprise a group of six rare neurometabolic disorders characterized by insufficient synthesis of the monoamine neurotransmitters dopamine and serotonin due to a disturbance of BH4 biosynthesis or recycling. Hyperphenylalaninemia (HPA) is the first diagnostic hallmark for most BH4 deficiencies, apart from autosomal dominant guanosine triphosphate cyclohydrolase I deficiency and sepiapterin reductase deficiency. Early supplementation of neurotransmitter precursors and where appropriate, treatment of HPA results in significant improvement of motor and cognitive function. Management approaches differ across the world and therefore these guidelines have been developed aiming to harmonize and optimize patient care. Representatives of the International Working Group on Neurotransmitter related Disorders (iNTD) developed the guidelines according to the SIGN (Scottish Intercollegiate Guidelines Network) methodology by evaluating all available evidence for the diagnosis and treatment of BH4 deficiencies. Conclusion Although the total body of evidence in the literature was mainly rated as low or very low, these consensus guidelines will help to harmonize clinical practice and to standardize and improve care for BH4 deficient patients.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Tetrahydrobiopterin deficiencyBH4NeurotransmitterGuanosine triphosphate cyclohydrolase deficiency6- pyruvoyltetrahydropterin synthase deficiencySepiapterin reductase deficiencyPterin-4-alpha-carbinolamine dehydratase deficiencyDihydropteridine reductase deficiencyHyperphenylalaninemiaiNTDConsensus guidelinesSIGNFenilcetonuriasNeurotransmisoresConsensoGuíaMedical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 2-Ring::Pteridines::Pterins::BiopterinMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Neurologic Manifestations::Dyskinesias::DystoniaMedical Subject Headings::Diseases::Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Genetic Diseases, Inborn::Metabolism, Inborn ErrorsMedical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Metabolism, Inborn Errors::Brain Diseases, Metabolic, Inborn::PhenylketonuriasMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Neurotransmitter AgentsMedical Subject Headings::Psychiatry and Psychology::Behavior and Behavior Mechanisms::Psychology, Social::Group Processes::ConsensusMedical Subject Headings::Publication Type::Publication Formats::Guidelinereview article32456656open access10.1186/s13023-020-01379-81750-1172PMC7251883