@article{cbf19ef08cf6472097f5e3dcfdf981f4,
title = "Neurocognitive outcome and mental health in children with tyrosinemia type 1 and phenylketonuria: A comparison between two genetic disorders affecting the same metabolic pathway",
abstract = "Tyrosinemia type 1 (TT1) and phenylketonuria (PKU) are both inborn errors of phenylalanine-tyrosine metabolism. Neurocognitive and behavioral outcomes have always featured in PKU research but received less attention in TT1 research. This study aimed to investigate and compare neurocognitive, behavioral, and social outcomes of treated TT1 and PKU patients. We included 33 TT1 patients (mean age 11.24 years; 16 male), 31 PKU patients (mean age 10.84; 14 male), and 58 age- and gender-matched healthy controls (mean age 10.82 years; 29 male). IQ (Wechsler-subtests), executive functioning (the Behavioral Rating Inventory of Executive Functioning), mental health (the Achenbach-scales), and social functioning (the Social Skills Rating System) were assessed. Results of TT1 patients, PKU patients, and healthy controls were compared using Kruskal-Wallis tests with post-hoc Mann-Whitney U tests. TT1 patients showed a lower IQ and poorer executive functioning, mental health, and social functioning compared to healthy controls and PKU patients. PKU patients did not differ from healthy controls regarding these outcome measures. Relatively poor outcomes for TT1 patients were particularly evident for verbal IQ, BRIEF dimensions {"}working memory{"}, {"}plan and organize{"} and {"}monitor{"}, ASEBA dimensions {"}social problems{"} and {"}attention problems{"}, and for the SSRS {"}assertiveness{"} scale (all p values <0.001). To conclude, TT1 patients showed cognitive impairments on all domains studied, and appeared to be significantly more affected than PKU patients. More attention should be paid to investigating and monitoring neurocognitive outcome in TT1 and research should focus on explaining the underlying pathophysiological mechanism.",
keywords = "Amsterdam Neuropsychological Tasks, executive functions, neurocognitive outcome, phenylketonuria, social cognition, tyrosinemia type 1, TREATED PHENYLKETONURIA, ADULT PHENYLKETONURIA, NTBC TREATMENT, PHENYLALANINE, NITISINONE, INHIBITION, MANAGEMENT, PROFILE",
author = "{van Vliet}, K. and {van Ginkel}, W.G. and R. Jahja and A. Daly and A. MacDonald and S. Santra and {De Laet}, C. and P.J. Goyens and R. Vara and Y. Rahman and D. Cassiman and F. Eyskens and C. Timmer and N. Mumford and P. Gissen and J. Bierau and {van Hasselt}, P.M. and G. Wilcox and A.A.M. Morris and E.A. Jameson and {de la Parra}, A. and C. Arias and M.I. Garcia and V. Cornejo and A.M. Bosch and C.E.M. Hollak and M.E. Rubio-Gozalbo and M.C.G.J. Brouwers and F.C. Hofstede and {de Vries}, M.C. and M.C.H. Janssen and {van der Ploeg}, A.T. and J.G. Langendonk and S.C.J. Huijbregts and {van Spronsen}, F.J.",
note = "Funding Information: Willem G. van Ginkel has received speakers honoraria and research grants from SOBI. Rianne Jahja has received honoraria as a speaker and consultant for Merck Serono and Biomarin. Anne Daly received research funding and or honoraria from Nutricia, Vitaflo International, Metax, APR, and is a member of the Advisory Board for Meta Health. Anita MacDonald received research funding and/or honoraria from Nutricia, Vitaflo International, Biomarin, Metax, Nestle, APR, Merck Serono, and is a member of the Advisory Board Element (Danone–Nutricia) and Meta Health. Corinne De Laet received travel grants, advisory board fees, and speaker's honoraria from SOBI, Shire, Sanofi‐Genzyme, and Biomarin. Gisela Wilcox has received travel grants from Genzyme, Biomarin, Alexion, Shire & Amicus, speaker honoraria from Vitaflo, Biomarin, Shire, Nutricia, and Sanofi‐Genzyme, research grants from the MPS society (UK), and advisory board membership with Biomarin, Medical Advisory Panel membership for the National Society for PKU (NSPKU), Meta Healthcare, Nutricia, and consultancies for Dimension Therapeutics. Stephan C. J. Huijbregts has participated in strategic advisory boards and received grants and honoraria as a consultant and/or speaker from Biomarin, Merck Serono SA, Homology Medicines, and Nutricia. Francjan J. van Spronsen has received research grants, advisory board fees, and/or speaker's honoraria from Nutricia Research, Merck‐Serono, Biomarin, Codexis, Moderna, Alexion, Vitaflo, MendeliKABS, Promethera, SOBI, APR, and ARLA Foods Int. Kimber van Vliet, Saikat Santra, Philippe J. Goyens, Roshni Vara, Yusof Rahman, David Cassiman, Francois Eyskens, Corrie Timmer, Nicky Mumford, Paul Gissen, J{\"o}rgen Bierau, Peter M. van Hasselt, Andrew A. M. Morris, Elisabeth A. Jameson, Alicia de la Parra, Carolina Arias, Maria I. Garcia, Annet M. Bosch, Carla E. M. Hollak, M. Estela Rubio‐Gozalbo, Martijn C. G. J. Brouwers, Floris C. Hofstede, Maaike C. de Vries, Mirian C. H. Janssen, Ans T. van der Ploeg, and Janneke G. Langendonk; did not declare any conflicts of interest. Funding Information: This study has been funded by SOBI and the Tyrosinemia Foundation. The authors confirm independence from the sponsors; the content of the article has not been influenced by the sponsors. Publisher Copyright: {\textcopyright} 2022 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.",
year = "2022",
month = sep,
doi = "10.1002/jimd.12528",
language = "English",
volume = "45",
pages = "952--962",
journal = "Journal of Inherited Metabolic Disease",
issn = "0141-8955",
publisher = "Springer",
number = "5",
}