Neurocognitive outcome and mental health in children with tyrosinemia type 1 and phenylketonuria: A comparison between two genetic disorders affecting the same metabolic pathway

Kimber van Vliet, Willem G. van Ginkel, Rianne Jahja, Anne Daly, Anita MacDonald, Saikat Santra, Corinne De Laet, Philippe J. Goyens, Roshni Vara, Yusof Rahman, David Cassiman, Francois Eyskens, Corrie Timmer, Nicky Mumford, Paul Gissen, Jörgen Bierau, Peter M. van Hasselt, Gisela Wilcox, Andrew A.M. Morris, Elisabeth A. JamesonAlicia de la Parra, Carolina Arias, Maria I. Garcia, Veronica Cornejo, 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, Janneke G. Langendonk, Stephan C.J. Huijbregts, Francjan J. van Spronsen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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.

Original languageEnglish
Pages (from-to)952-962
Number of pages11
JournalJournal of Inherited Metabolic Disease
Issue number5
Early online date20 Jun 2022
Publication statusPublished - Sept 2022


  • Amsterdam Neuropsychological Tasks
  • executive functions
  • neurocognitive outcome
  • phenylketonuria
  • social cognition
  • tyrosinemia type 1


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