Kimber van Vliet1, Willem G van Ginkel1, Rianne Jahja1, Anne Daly2, Anita MacDonald2, Corinne De Laet3, Roshni Vara4, Yusof Rahman5, David Cassiman6, Francois Eyskens7, Corrie Timmer8, Nicky Mumford9, Jörgen Bierau10, Peter M van Hasselt11, Paul Gissen9, Philippe J Goyens3, Patrick J McKiernan2, Gisela Wilcox12,13, Andrew A M Morris14, Elisabeth A Jameson14, Stephan C J Huijbregts15, Francjan J van Spronsen16. 1. Beatrix Children's Hospital, Groningen, Division of Metabolic Diseases, University of Groningen, University Medical Center Groningen, CA33, PO box 30.001, 9700 RB, Groningen, Netherlands. 2. Birmingham Children's Hospital, Birmingham, UK. 3. Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles, Brussels, Belgium. 4. Evelina London Children's Hospital, London, UK. 5. Guy's and St. Thomas' Hospital, London, UK. 6. University Hospital Gasthuisberg, University of Leuven, Leuven, Belgium. 7. Kon. Mathilde Moeder- en Kindcentrum, University Hospital of Antwerp, Antwerp, Belgium. 8. Academic Medical Center, Amsterdam, Netherlands. 9. Great Ormond Street Hospital, London, UK. 10. Maastricht University Medical Center, Maastricht, Netherlands. 11. Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, Utrecht, Netherlands. 12. School of Medical Sciences, Faculty of Biology Medicine & Health, University of Manchester, Manchester, UK. 13. The Mark Holland Metabolic Unit, Salford Royal Foundation NHS Trust, Greater Manchester, M6 8HD, Salford, UK. 14. Willink Metabolic Unit, Manchester Centre for Genomic Medicine, Manchester University Hospitals NHS Foundation Trust, St Mary's Hospital, Manchester, UK. 15. University of Leiden, Clinical Child and Adolescent Studies: Neurodevelopmental Disorders, Leiden, Netherlands. 16. Beatrix Children's Hospital, Groningen, Division of Metabolic Diseases, University of Groningen, University Medical Center Groningen, CA33, PO box 30.001, 9700 RB, Groningen, Netherlands. f.j.van.spronsen@umcg.nl.
Abstract
BACKGROUND: Treatment with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) and dietary phenylalanine and tyrosine restriction improves physical health and life expectancy in Tyrosinemia type 1 (TT1). However, neurocognitive outcome is suboptimal. This study aimed to investigate behavior problems and health-related quality of life (HR-QoL) in NTBC-dietary-treated TT1 and to relate this to phenylalanine and tyrosine concentrations. RESULTS: Thirty-one TT1 patients (19 males; mean age 13.9 ± 5.3 years) were included in this study. Emotional and behavioral problems, as measured by the Achenbach System of Empirically Based Assessment, were present in almost all domains. Attention and thought problems were particularly evident. HR-QoL was assessed by the TNO AZL Children's and Adults QoL questionnaires. Poorer HR-QoL as compared to reference populations was observed for the domains: independent daily functioning, cognitive functioning and school performance, social contacts, motor functioning, and vitality. Both internalizing and externalizing behavior problems were associated with low phenylalanine (and associated lower tyrosine) concentrations during the first year of life. In contrast, high tyrosine (and associated higher phenylalanine) concentrations during life and specifically the last year before testing were associated with more internalizing behavior and/or HR-QoL problems. CONCLUSIONS: TT1 patients showed several behavior problems and a lower HR-QoL. Associations with metabolic control differed for different age periods. This suggests the need for continuous fine-tuning and monitoring of dietary treatment to keep phenylalanine and tyrosine concentrations within target ranges in NTBC-treated TT1 patients.
BACKGROUND: Treatment with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) and dietary phenylalanine and tyrosine restriction improves physical health and life expectancy in Tyrosinemia type 1 (TT1). However, neurocognitive outcome is suboptimal. This study aimed to investigate behavior problems and health-related quality of life (HR-QoL) in NTBC-dietary-treated TT1 and to relate this to phenylalanine and tyrosine concentrations. RESULTS: Thirty-one TT1patients (19 males; mean age 13.9 ± 5.3 years) were included in this study. Emotional and behavioral problems, as measured by the Achenbach System of Empirically Based Assessment, were present in almost all domains. Attention and thought problems were particularly evident. HR-QoL was assessed by the TNO AZLChildren's and Adults QoL questionnaires. Poorer HR-QoL as compared to reference populations was observed for the domains: independent daily functioning, cognitive functioning and school performance, social contacts, motor functioning, and vitality. Both internalizing and externalizing behavior problems were associated with low phenylalanine (and associated lower tyrosine) concentrations during the first year of life. In contrast, high tyrosine (and associated higher phenylalanine) concentrations during life and specifically the last year before testing were associated with more internalizing behavior and/or HR-QoL problems. CONCLUSIONS:TT1patients showed several behavior problems and a lower HR-QoL. Associations with metabolic control differed for different age periods. This suggests the need for continuous fine-tuning and monitoring of dietary treatment to keep phenylalanine and tyrosine concentrations within target ranges in NTBC-treated TT1patients.
Entities:
Keywords:
Behavior problems; Health related-quality of life; Phenylalanine; Tyrosine; Tyrosinemia type 1
Authors: Evangelos Handakas; Yiwen Xu; Alexa Blair Segal; Maria Carmen Huerta; Kirsty Bowman; Laura D Howe; Franco Sassi; Oliver Robinson Journal: Front Genet Date: 2022-08-31 Impact factor: 4.772
Authors: 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 Jameson; Alicia 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 Journal: J Inherit Metab Dis Date: 2022-06-30 Impact factor: 4.750