{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T18:06:38Z","timestamp":1792433198555,"version":"4.5.0"},"reference-count":45,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T00:00:00Z","timestamp":1682899200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T00:00:00Z","timestamp":1682899200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T00:00:00Z","timestamp":1682899200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T00:00:00Z","timestamp":1682899200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T00:00:00Z","timestamp":1682899200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T00:00:00Z","timestamp":1682899200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T00:00:00Z","timestamp":1682899200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100009422","name":"National PKU Alliance","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009422","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Genetics and Metabolism"],"published-print":{"date-parts":[[2023,5]]},"DOI":"10.1016\/j.ymgme.2023.107579","type":"journal-article","created":{"date-parts":[[2023,4,8]],"date-time":"2023-04-08T21:06:30Z","timestamp":1680987990000},"page":"107579","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":12,"title":["Neuropsychological assessment of adults with phenylketonuria using the NIH toolbox"],"prefix":"10.1016","volume":"139","author":[{"given":"Shawn E.","family":"Christ","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayley E.","family":"Clocksin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maia","family":"Zalik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin D.","family":"Goodlett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie J.","family":"Sacharow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily E.","family":"Abbene","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ymgme.2023.107579_bb0005","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1542\/peds.20.2.290","article-title":"The variability in manifestations of untreated patients with phenylketonuria (phenylpyruvic aciduria)","volume":"20","author":"Paine","year":"1957","journal-title":"Pediatrics."},{"key":"10.1016\/j.ymgme.2023.107579_bb0010","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1097\/00005072-195007000-00004","article-title":"Neuropathological findings in phenylpyruvic oligophrenia (phenylketonuria)","volume":"9","author":"Alvord","year":"1950","journal-title":"J. Neuropathol. Exp. Neurol."},{"issue":"Suppl. 2","key":"10.1016\/j.ymgme.2023.107579_bb0015","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/BF01799701","article-title":"Dietary problems of phenylketonuria: effect on CNS transmitters and their possible role in behaviour and neuropsychological function","volume":"9","author":"G\u00fcttler","year":"1986","journal-title":"J. Inherit. Metab. Dis."},{"key":"10.1016\/j.ymgme.2023.107579_bb0020","first-page":"159","article-title":"The neurochemistry of phenylketonuria","author":"Surtees","year":"2000","journal-title":"Eur. J. Pediatr. Suppl."},{"key":"10.1016\/j.ymgme.2023.107579_bb0025","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/0005-2787(78)90214-9","article-title":"Experimentally induced and natural recovery from the effects of phenylalanine on brain protein synthesis","volume":"517","author":"Hughes","year":"1978","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.ymgme.2023.107579_bb0030","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1007\/s10571-011-9693-2","article-title":"Oxidative stress in phenylketonuria: what is the evidence?","volume":"31","author":"Ribas","year":"2011","journal-title":"Cell. Mol. Neurobiol."},{"key":"10.1016\/j.ymgme.2023.107579_bb0035","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.ymgme.2008.12.019","article-title":"Phenylketonuria: high plasma phenylalanine decreases cerebral protein synthesis","volume":"96","author":"Hoeksma","year":"2009","journal-title":"Mol. Genet. Metab."},{"issue":"Suppl. 1","key":"10.1016\/j.ymgme.2023.107579_bb0040","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/j.ymgme.2009.10.005","article-title":"White matter pathology in phenylketonuria","volume":"99","author":"Anderson","year":"2010","journal-title":"Mol. Genet. Metab."},{"key":"10.1016\/j.ymgme.2023.107579_bb0045","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.ymgme.2016.02.004","article-title":"Morphometric analysis of gray matter integrity in individuals with early-treated phenylketonuria","volume":"118","author":"Christ","year":"2016","journal-title":"Mol. Genet. Metab."},{"key":"10.1016\/j.ymgme.2023.107579_bb0050","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.ymgme.2012.08.007","article-title":"A volumetric study of basal ganglia structures in individuals with early-treated phenylketonuria","volume":"107","author":"Bodner","year":"2012","journal-title":"Mol. Genet. Metab."},{"key":"10.1016\/j.ymgme.2023.107579_bb0055","article-title":"The effects of early-treated phenylketonuria on volumetric measures of the cerebellum","volume":"25","author":"Aldridge","year":"2020","journal-title":"Mol. Genet. Metab. Rep."},{"key":"10.1016\/j.ymgme.2023.107579_bb0060","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1002\/jimd.12049","article-title":"Cerebrospinal fluid biogenic amines depletion and brain atrophy in adult patients with phenylketonuria","volume":"42","author":"Pilotto","year":"2019","journal-title":"J. Inherit. Metab. Dis."},{"key":"10.1016\/j.ymgme.2023.107579_bb0065","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.ymgme.2022.09.006","article-title":"The relationship between metabolic control and basal ganglia morphometry and function in individuals with early-treated phenylketonuria","volume":"137","author":"Brown","year":"2022","journal-title":"Mol. Genet. Metab."},{"key":"10.1016\/j.ymgme.2023.107579_bb0070","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.ymgme.2020.12.001","article-title":"Inter- and intra-tract analysis of white matter abnormalities in individuals with early-treated phenylketonuria (PKU)","volume":"132","author":"Clocksin","year":"2021","journal-title":"Mol. Genet. Metab."},{"key":"10.1016\/j.ymgme.2023.107579_bb0075","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1080\/87565641.2016.1243109","article-title":"Systematic review and meta-analysis of neuropsychiatric symptoms and executive functioning in adults with phenylketonuria","volume":"41","author":"Bilder","year":"2016","journal-title":"Dev. Neuropsychol."},{"key":"10.1016\/j.ymgme.2023.107579_bb0080","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1186\/s13023-018-0893-4","article-title":"A systematic review of cognitive functioning in early treated adults with phenylketonuria","volume":"13","author":"Hofman","year":"2018","journal-title":"Orphanet. J. Rare Dis."},{"issue":"Suppl. 1","key":"10.1016\/j.ymgme.2023.107579_bb0085","doi-asserted-by":"crossref","first-page":"S22","DOI":"10.1016\/j.ymgme.2009.10.007","article-title":"Executive function in early-treated phenylketonuria: profile and underlying mechanisms","volume":"99","author":"Christ","year":"2010","journal-title":"Mol. Genet. Metab."},{"key":"10.1016\/j.ymgme.2023.107579_bb0090","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s11065-007-9021-2","article-title":"Meta-analysis of neuropsychological symptoms of adolescents and adults with PKU","volume":"17","author":"Moyle","year":"2007","journal-title":"Neuropsychol. Rev."},{"key":"10.1016\/j.ymgme.2023.107579_bb0095","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.jpeds.2013.12.015","article-title":"Neurocognitive evidence for revision of treatment targets and guidelines for phenylketonuria","volume":"164","author":"Jahja","year":"2014","journal-title":"J. Pediatr."},{"key":"10.1016\/j.ymgme.2023.107579_bb0100","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.ymgme.2007.05.006","article-title":"Phenylalanine blood levels and clinical outcomes in phenylketonuria: a systematic literature review and meta-analysis","volume":"92","author":"Waisbren","year":"2007","journal-title":"Mol. Genet. Metab."},{"key":"10.1016\/j.ymgme.2023.107579_bb0105","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1037\/neu0000336","article-title":"The impact of phenylalanine levels on cognitive outcomes in adults with phenylketonuria: effects across tasks and developmental stages","volume":"31","author":"Romani","year":"2017","journal-title":"Neuropsychology."},{"key":"10.1016\/j.ymgme.2023.107579_bb0110","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/S0140-6736(07)61234-3","article-title":"Efficacy of sapropterin dihydrochloride (tetrahydrobiopterin, 6R-BH4) for reduction of phenylalanine concentration in patients with phenylketonuria: a phase III randomised placebo-controlled study","volume":"370","author":"Levy","year":"2007","journal-title":"Lancet."},{"key":"10.1016\/j.ymgme.2023.107579_bb0115","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.ymgme.2018.06.002","article-title":"Phenylalanine ammonia lyase (PAL): from discovery to enzyme substitution therapy for phenylketonuria","volume":"124","author":"Levy","year":"2018","journal-title":"Mol. Genet. Metab."},{"key":"10.1016\/j.ymgme.2023.107579_bb0120","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/mono.12031","article-title":"I. NIH toolbox cognition battery (CB): introduction and pediatric data","volume":"78","author":"Weintraub","year":"2013","journal-title":"Monogr. Soc. Res. Child Dev."},{"key":"10.1016\/j.ymgme.2023.107579_bb0125","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1212\/WNL.0b013e3182872e5f","article-title":"NIH toolbox for assessment of neurological and behavioral function","volume":"80","author":"Gershon","year":"2013","journal-title":"Neurology."},{"key":"10.1016\/j.ymgme.2023.107579_bb0130","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1017\/S1355617715000351","article-title":"Demographically corrected normative standards for the English version of the NIH toolbox cognition battery","volume":"21","author":"Casaletto","year":"2015","journal-title":"J. Int. Neuropsychol. Soc. JINS"},{"key":"10.1016\/j.ymgme.2023.107579_bb0135","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1017\/S135561771500137X","article-title":"Demographically corrected normative standards for the Spanish language version of the NIH toolbox cognition battery","volume":"22","author":"Casaletto","year":"2016","journal-title":"J. Int. Neuropsychol. Soc. JINS"},{"key":"10.1016\/j.ymgme.2023.107579_bb0140","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1017\/S1355617714000241","article-title":"Reliability and validity of composite scores from the NIH toolbox cognition battery in adults","volume":"20","author":"Heaton","year":"2014","journal-title":"J. Int. Neuropsychol. Soc. JINS"},{"key":"10.1016\/j.ymgme.2023.107579_bb0145","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s11689-016-9167-4","article-title":"The NIH toolbox cognitive battery for intellectual disabilities: three preliminary studies and future directions","volume":"8","author":"Hessl","year":"2016","journal-title":"J. Neurodev. Disord."},{"key":"10.1016\/j.ymgme.2023.107579_bb0150","doi-asserted-by":"crossref","first-page":"e1229","DOI":"10.1212\/WNL.0000000000009131","article-title":"Validation of the NIH toolbox cognitive battery in intellectual disability","volume":"94","author":"Shields","year":"2020","journal-title":"Neurology."},{"key":"10.1016\/j.ymgme.2023.107579_bb0155","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1093\/arclin\/acx020","article-title":"Validation of the NIH toolbox in individuals with neurologic disorders","volume":"32","author":"Carlozzi","year":"2017","journal-title":"Arch. Clin. Neuropsychol. Off. J. Natl. Acad. Neuropsychol."},{"key":"10.1016\/j.ymgme.2023.107579_bb0160","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1037\/rep0000183","article-title":"Factor structure of the NIH toolbox cognition battery in individuals with acquired brain injury","volume":"62","author":"Tulsky","year":"2017","journal-title":"Rehabil. Psychol."},{"key":"10.1016\/j.ymgme.2023.107579_bb0165","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1002\/aur.2399","article-title":"Using the NIH toolbox to assess cognition in adolescents and young adults with autism spectrum disorders","volume":"14","author":"Solomon","year":"2021","journal-title":"Autism Res. Off. J. Int. Soc. Autism Res."},{"key":"10.1016\/j.ymgme.2023.107579_bb0170","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1007\/s10803-021-04965-2","article-title":"Evaluating the feasibility of the NIH toolbox cognition battery for autistic children and adolescents","volume":"52","author":"Jones","year":"2022","journal-title":"J. Autism Dev. Disord."},{"key":"10.1016\/j.ymgme.2023.107579_bb0175","doi-asserted-by":"crossref","DOI":"10.1002\/pbc.27899","article-title":"Higher executive abilities following a blood transfusion in children and young adults with sickle cell disease","volume":"66","author":"Hood","year":"2019","journal-title":"Pediatr. Blood Cancer"},{"key":"10.1016\/j.ymgme.2023.107579_bb0180","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1016\/j.dadm.2018.10.002","article-title":"Utility of the NIH toolbox for assessment of prodromal Alzheimer\u2019s disease and dementia","volume":"10","author":"Hackett","year":"2018","journal-title":"Alzheimers Dement. Amst. Neth."},{"key":"10.1016\/j.ymgme.2023.107579_bb0185","article-title":"Motor control and learning in individuals with early-treated phenylketonuria. [published online ahead of print July 29, 2021]","author":"Christ","year":"2023","journal-title":"Neuropsychology."},{"key":"10.1016\/j.ymgme.2023.107579_bb0190","doi-asserted-by":"crossref","DOI":"10.1017\/S1355617722000686","article-title":"A comprehensive assessment of neurocognitive and psychological functioning in adults with early-treated phenylketonuria. [published online ahead of print September 22, 2016]","author":"Clocksin","year":"2023","journal-title":"J. Int. Neuropsychol. Soc. JINS"},{"key":"10.1016\/j.ymgme.2023.107579_bb0195","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1037\/neu0000337","article-title":"Cognitive outcomes in early-treated adults with phenylketonuria (PKU): a comprehensive picture across domains","volume":"31","author":"Palermo","year":"2017","journal-title":"Neuropsychology."},{"key":"10.1016\/j.ymgme.2023.107579_bb0200","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1080\/87565640701375963","article-title":"Are neuropsychological impairments in children with early-treated phenylketonuria (PKU) related to white matter abnormalities or elevated phenylalanine levels?","volume":"32","author":"Anderson","year":"2007","journal-title":"Dev. Neuropsychol."},{"key":"10.1016\/j.ymgme.2023.107579_bb0205","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1017\/S1355617719000146","article-title":"Neuropsychological profile of children with early and continuously treated phenylketonuria: systematic review and future approaches","volume":"25","author":"Canton","year":"2019","journal-title":"J. Int. Neuropsychol. Soc. JINS"},{"key":"10.1016\/j.ymgme.2023.107579_bb0210","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.neubiorev.2008.11.001","article-title":"Neuropsychological speed tests and blood phenylalanine levels in patients with phenylketonuria: a meta-analysis","volume":"33","author":"Albrecht","year":"2009","journal-title":"Neurosci. Biobehav. Rev."},{"key":"10.1016\/j.ymgme.2023.107579_bb0215","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.ymgme.2012.11.003","article-title":"A diversified approach for PKU treatment: routine screening yields high incidence of psychiatric distress in phenylketonuria clinics","volume":"108","author":"Burton","year":"2013","journal-title":"Mol. Genet. Metab."},{"key":"10.1016\/j.ymgme.2023.107579_bb0220","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1542\/peds.99.3.345","article-title":"Psychiatric disorders in adult patients with early-treated phenylketonuria","volume":"99","author":"Pietz","year":"1997","journal-title":"Pediatrics."},{"key":"10.1016\/j.ymgme.2023.107579_bb0225","doi-asserted-by":"crossref","first-page":"S76","DOI":"10.1212\/WNL.0b013e3182872e11","article-title":"Emotion assessment using the NIH toolbox","volume":"80","author":"Salsman","year":"2013","journal-title":"Neurology."}],"container-title":["Molecular Genetics and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1096719223002093?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1096719223002093?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T23:53:41Z","timestamp":1761090821000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1096719223002093"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5]]},"references-count":45,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,5]]}},"alternative-id":["S1096719223002093"],"URL":"https:\/\/doi.org\/10.1016\/j.ymgme.2023.107579","relation":{},"ISSN":["1096-7192"],"issn-type":[{"value":"1096-7192","type":"print"}],"subject":[],"published":{"date-parts":[[2023,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Neuropsychological assessment of adults with phenylketonuria using the NIH toolbox","name":"articletitle","label":"Article Title"},{"value":"Molecular Genetics and Metabolism","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ymgme.2023.107579","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"107579"}}