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

• Published in: Journal of inherited metabolic disease Vol. 45; no. 5; pp. 952 - 962
• Main Authors: Vliet, Kimber, Ginkel, Willem G., Jahja, Rianne, Daly, Anne, MacDonald, Anita, Santra, Saikat, De Laet, Corinne, Goyens, Philippe J., Vara, Roshni, Rahman, Yusof, Cassiman, David, Eyskens, Francois, Timmer, Corrie, Mumford, Nicky, Gissen, Paul, Bierau, Jörgen, Hasselt, Peter M., Wilcox, Gisela, Morris, Andrew A. M., Jameson, Elisabeth A., Parra, Alicia, Arias, Carolina, Garcia, Maria I., Cornejo, Veronica, Bosch, Annet M., Hollak, Carla E. M., Rubio‐Gozalbo, M. Estela, Brouwers, Martijn C. G. J., Hofstede, Floris C., Vries, Maaike C., Janssen, Mirian C. H., Ploeg, Ans T., Langendonk, Janneke G., Huijbregts, Stephan C. J., Spronsen, Francjan J.
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.09.2022; Blackwell Publishing Ltd
• Subjects: Amsterdam Neuropsychological Tasks; Child; Cognition; Cognitive ability; Executive function; executive functions; Genetic disorders; Humans; Inborn errors of metabolism; Intelligence; Language; Male; Mental Health; Metabolic Networks and Pathways; Metabolic pathways; neurocognitive outcome; Neuropsychological Tests; Phenylalanine; Phenylketonuria; Phenylketonurias; Short term memory; social cognition; Tyrosine; tyrosinemia type 1; Tyrosinemias - genetics; neurocognitive outcome; Amsterdam Neuropsychological Tasks; social cognition; phenylketonuria; executive functions; tyrosinemia type 1
• ISSN: 0141-8955; 1573-2665; 1573-2665
• DOI: 10.1002/jimd.12528

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.