{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:47:34Z","timestamp":1790912854308,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["TR3\u2010119195"],"award-info":[{"award-number":["TR3\u2010119195"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JIMD Reports"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Achieving and maintaining metabolic control is critical for children with phenylalanine hydroxylase (PAH) deficiency. This retrospective longitudinal cohort study investigated metabolic control and monitoring frequency of children with PAH deficiency (\u2264\u200912\u2009years) treated at one of 12 pediatric metabolic centres across Canada. We abstracted data from medical charts and analyzed outcomes by age and diagnostic classification, using mixed effects regression. Of 215 children included in the study, 43% had a chart diagnosis of classic phenylketonuria (PKU); the remainder had a diagnosis of mild PKU or mild hyperphenylalaninemia (grouped as \u201cless severe PAH deficiency\u201d). During the first month of life, blood phenylalanine levels of children with classic PKU reached the target therapeutic range of 120\u2013360\u2009\u03bcmol\/L at a median age of 15\u2009days, but 74.3% and 32.9% had \u2265\u20091 and \u2265\u20093 values below 120\u2009\u03bcmol\/L, respectively. From age &gt;\u20091\u2009month to 12\u2009years, mean blood phenylalanine values were 260.6 and 236.7\u2009\u03bcmol\/L for children with classic PKU and less severe PAH deficiency, respectively, with a trend of increased blood phenylalanine levels with increasing age (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). Fewer children with classic PKU (37.2%) versus less severe PAH deficiency (77.9%) had &gt;\u200960% of values in the therapeutic range, indicating less optimal metabolic control. Frequency of blood phenylalanine testing and communication with metabolic centres decreased with age. Our findings suggest a need to better understand the reasons for blood phenylalanine variability across child age and disease severity in order to inform supports for children with PAH deficiency and their caregivers to maintain metabolic control.<\/jats:p>","DOI":"10.1002\/jmd2.70042","type":"journal-article","created":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T22:44:35Z","timestamp":1756766675000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Metabolic Control and Frequency of Clinical Monitoring Among Canadian Children With Phenylalanine Hydroxylase Deficiency: A Retrospective Cohort Study"],"prefix":"10.1002","volume":"66","author":[{"given":"Nataliya","family":"Yuskiv","sequence":"first","affiliation":[{"name":"Division of Biochemical Genetics, BC Children's Hospital, Department of Pediatrics University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ammar","family":"Saad","sequence":"additional","affiliation":[{"name":"School of Epidemiology and Public Health University of Ottawa  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth K.","family":"Potter","sequence":"additional","affiliation":[{"name":"School of Epidemiology and Public Health University of Ottawa  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Stockler\u2010Ipsiroglu","sequence":"additional","affiliation":[{"name":"Division of Biochemical Genetics, BC Children's Hospital, Department of Pediatrics University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Montreal Children's Hospital  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Hawken","sequence":"additional","affiliation":[{"name":"Methodological and Implementation Research Program Ottawa Hospital Research Institute  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kylie","family":"Tingley","sequence":"additional","affiliation":[{"name":"School of Epidemiology and Public Health University of Ottawa  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Pugliese","sequence":"additional","affiliation":[{"name":"ICES uOttawa Ottawa Hospital Research Institute  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Lamoureux","sequence":"additional","affiliation":[{"name":"The Children's Hospital of Eastern Ontario Research Institute  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1683-2912","authenticated-orcid":false,"given":"Andrea J.","family":"Chow","sequence":"additional","affiliation":[{"name":"School of Epidemiology and Public Health University of Ottawa  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan B.","family":"Kronick","sequence":"additional","affiliation":[{"name":"Division of Clinical and Metabolic Genetics, The Hospital for Sick Children University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kumanan","family":"Wilson","sequence":"additional","affiliation":[{"name":"School of Epidemiology and Public Health University of Ottawa  Ottawa Ontario Canada"},{"name":"The Children's Hospital of Eastern Ontario Research Institute  Ottawa Ontario Canada"},{"name":"Department of Medicine University of Ottawa  Ottawa Ontario Canada"},{"name":"Bruy\u00e8re Health Research Institute  Ottawa Ontario Canada"},{"name":"Ottawa Hospital Research Institute  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Feigenbaum","sequence":"additional","affiliation":[{"name":"Division of Clinical and Metabolic Genetics, The Hospital for Sick Children University of Toronto  Toronto Ontario Canada"},{"name":"Division of Genetics Rady Children's Hospital and the University of California  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharan","family":"Goobie","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Maritime Medical Genetics Service, IWK Health Dalhousie University  Halifax Nova Scotia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Inbar\u2010Feigenberg","sequence":"additional","affiliation":[{"name":"Division of Clinical and Metabolic Genetics, The Hospital for Sick Children University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5026-5531","authenticated-orcid":false,"given":"Julian","family":"Little","sequence":"additional","affiliation":[{"name":"School of Epidemiology and Public Health University of Ottawa  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8396-6764","authenticated-orcid":false,"given":"Saadet","family":"Mercimek\u2010Andrews","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine &amp; Dentistry University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Pender","sequence":"additional","affiliation":[{"name":"Genetics &amp; Metabolics McMaster Children's Hospital, Hamilton Health Sciences  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chitra","family":"Prasad","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (Section of Genetics and Metabolism) Western University London Health Sciences Centre  London Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Schulze","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Department of Biochemistry University of Toronto  Toronto Ontario Canada"},{"name":"The Hospital for Sick Children  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yannis","family":"Trakadis","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Specialized Medicine McGill University Health Center  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Ho","sequence":"additional","affiliation":[{"name":"Division of Biochemical Genetics, BC Children's Hospital, Department of Pediatrics University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilary","family":"Vallance","sequence":"additional","affiliation":[{"name":"Department of Pathology and Lab Medicine BC Children's Hospital  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Austin","sequence":"additional","affiliation":[{"name":"Division of Clinical and Metabolic Genetics, The Hospital for Sick Children University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Vandersteen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Maritime Medical Genetics Service, IWK Health Dalhousie University  Halifax Nova Scotia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea C.","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Children's Hospital of Eastern Ontario  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl","family":"Rockman\u2010Greenberg","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Child Health, Max Rady College of Medicine University of Manitoba  Winnipeg Manitoba Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aizeddin A.","family":"Mhanni","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Child Health, Max Rady College of Medicine University of Manitoba  Winnipeg Manitoba Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pranesh","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"The Children's Hospital of Eastern Ontario Research Institute  Ottawa Ontario Canada"},{"name":"Department of Pediatrics Children's Hospital of Eastern Ontario  Ottawa Ontario Canada"},{"name":"Department of Pediatrics University of Ottawa  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(10)60961\u20100"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/iub.1150"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22980"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2022.12.005"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2013.179"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2013.157"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2024.101289"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2013.07.079"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.4238\/vol9-1gmr670"},{"key":"e_1_2_12_11_1","first-page":"18087","volume-title":"PKU and BH4: Advances in Phenylketonuria and Tetrahydrobiopterin","author":"Lindner M.","year":"2006"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010010\u20109224\u20101"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijns6030059"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010017\u20100685\u20102"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1159\/000312813"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(16)30320-5"},{"key":"e_1_2_12_17_1","unstructured":"A. C.Inwood K.Lewis andS.Balasubramaniam \u201cAustralasian Consensus Guidelines for the Management of Phenylketonuria (PKU) Throughout the Lifespan \u201d2017."},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010011\u20109329\u20101"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2007.05.006"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010020\u201001358\u2010z"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbi.2008.08.010"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbi.2019.103208"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2020.06.006"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2013.01.007"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2019.12.007"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2017.09.003"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651\u20102227.1994.tb13456.x"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu16132064"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2017-0015"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2024.108541"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678707.2018.1536541"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2014.01.012"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2008.06.014"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2020\u2010037747"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bios.2021.113764"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2020.100599"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.3305\/nh.2010.25.1.4482"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2010.06.015"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2013.09.001"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/children11040447"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2010.05.017"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11065\u2010007\u20109021\u20102"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2017.04.006"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.26635\/6965.5949"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2017.04.006"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/8904_2017_52"}],"container-title":["JIMD Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmd2.70042","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T05:47:33Z","timestamp":1758865653000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmd2.70042"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":45,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1002\/jmd2.70042"],"URL":"https:\/\/doi.org\/10.1002\/jmd2.70042","archive":["Portico"],"relation":{},"ISSN":["2192-8312","2192-8312"],"issn-type":[{"value":"2192-8312","type":"print"},{"value":"2192-8312","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9]]},"assertion":[{"value":"2025-06-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70042"}}