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PAH impairment causes phenylalanine accumulation in the blood and brain, with a broad spectrum of pathophysiological and neurological consequences for patients. Prevalence of disease varies, with peaks in some regions and countries, including Italy. A recent expert survey described the real-life of clinical practice for PKU in Italy, revealing inhomogeneities in disease management, particularly concerning approach to pharmacotherapy with sapropterin hydrochloride, analogous of the natural PAH co-factor, allowing disease control in a subset of patients. Therefore, the purpose of this paper is to continue the work initiated with the expert survey paper, to provide national guidances aiming to harmonize and optimize patient care at a national level.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Participants<\/jats:title>\n                <jats:p>The Consensus Group, convened by 10 Steering Committee members, consisted of a multidisciplinary crowd of 46 experts in the management of PKU in Italy.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Consensus process<\/jats:title>\n                <jats:p>The Steering Committee met in a series of virtual meeting in order to discuss on clinical focuses to be developed and analyzed in guidance statements, on the basis of expert practice based evidence, large systematic literature review previously performed in the expert survey paper, and evidence based consensus published. Statements were re-discussed and refined during consensus conferences in the widest audience of experts, and finally submitted to the whole consensus group for a modified-Delphi voting.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Seventy three statements, divided in two main clinical areas, PKU management and Pharmacotherapy, achieved large consensus in a multidisciplinary group of expert in different aspects of disease. Importantly, these statements involve guidances for the use of sapropterin dihydrochloride, still not sufficiently implemented in Italy, and a set of good practice to approach the use of novel enzyme replacement treatment pegvaliase.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>This evidence-based consensus provides a minimum set of guidances for disease management to be implemented in all PKU centers. Moreover, these guidances represent the first statement for sapropterin dihydrochloride use, implementation and standardization in Italy, and a guide for approaching pegvaliase treatment at a national level on a consistent basis.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13023-021-02086-8","type":"journal-article","created":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T10:02:55Z","timestamp":1637056975000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Italian national consensus statement on management and pharmacological treatment of phenylketonuria"],"prefix":"10.1186","volume":"16","author":[{"given":"Alberto","family":"Burlina","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7441-9248","authenticated-orcid":false,"given":"Giacomo","family":"Biasucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Teresa","family":"Carbone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Cazzorla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Paci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Pochiero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Spada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albina","family":"Tummolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juri","family":"Zuvadelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Leuzzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,11,16]]},"reference":[{"issue":"2","key":"2086_CR1","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.ajhg.2020.06.006","volume":"107","author":"A Hillert","year":"2020","unstructured":"Hillert A, Anikster Y, Belanger-Quintana A, Burlina A, Burton BK, Carducci C, et al. 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Biasucci has received advisory board honoraria, speaker fees and travel support from BioMarin, SOBI, Vitaflo, PIAM Farmaceutici, Recordati Rare Diseases. A. Burlina has received advisory board honoraria, speaker fees and travel support from BioMarin, Nutricia, PIAM Farmaceutici, Sanofi Genzyme, Takeda Shire, Recordati Rare Diseases. M.T. Carbone has received advisory board honoraria and travel support from BioMarin, PIAM Farmaceutici, APR, Vitaflo. C. Cazzorla has received advisory board honoraria from BioMarin. V. Leuzzi has received advisory board honoraria, speaker fee and travel support from Nutricia, BioMarin, PTC, PIAM Farmaceutici. S. Paci has received advisory board honoraria, speaker fee and travel support from BioMarin, Nutricia, APR, Mamoxi, PIAM, Recordati Rare Diseases. F. Pochiero has received advisory board honoraria from BioMarin. M. Spada has received in the last two years advisory board honoraria, speaker fees and travel support from Sanofi, PIAM Farmaceutici, Takeda Shire, BioMarin, Nutricia, Sobi, Amicus, APR, Recordati Rare Diseases. A. Tummolo was invited advisor for BioMarin, Sanofi, Recordati and APR advisory boards. She received project funding from BioMarin. J. Zuvadelli has received advisory board honoraria, speaker fees and travel support from BioMarin, APR-Applied Pharma Research, Mamoxi and PIAM Farmaceutici.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"476"}}