Abstract
BackgroundTreatment 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.ResultsThirty-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.ConclusionsTT1 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.
Highlights
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)
Based on the existing literature on associations between metabolic control and behavioral outcomes in TT1 and phenylketonuria we focused on phenylalanine and tyrosine levels during three periods in life: the first year after birth, throughout lifetime, and the last year before assessment [5, 8, 13, 18, 19]
No significant correlations were observed between results on the Achenbach System of Empirically Based Assessment (ASEBA) questionnaires and lifetime plasma phenylalanine and tyrosine concentrations
Summary
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). 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. 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. Tyrosinemia type 1 (TT1; McKusick 276,700) is an inborn error of tyrosine catabolism, caused by fumarylacetoacetate hydrolase deficiency. This causes accumulation of toxic metabolites which can result in liver failure and hepatocellular carcinoma (HCC), renal tubular dysfunction and neurological porphyria-like crises [1]. Full list of author information is available at the end of the article phenylalanine was the only treatment to reduce the synthesis of toxic metabolites, while not preventing liver complications. The use of NTBC has undoubtedly improved outcome and life
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