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1.
J Inherit Metab Dis ; 45(5): 952-962, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35722880

RESUMEN

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.


Asunto(s)
Fenilcetonurias , Tirosinemias , Niño , Humanos , Masculino , Salud Mental , Redes y Vías Metabólicas , Pruebas Neuropsicológicas , Tirosinemias/genética
2.
Orphanet J Rare Dis ; 14(1): 285, 2019 12 04.
Artículo en Inglés | MEDLINE | ID: mdl-31801588

RESUMEN

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.


Asunto(s)
Ciclohexanonas/uso terapéutico , Nitrobenzoatos/uso terapéutico , Tirosinemias/sangre , Tirosinemias/tratamiento farmacológico , Adolescente , Adulto , Niño , Humanos , Masculino , Fenilalanina/sangre , Calidad de Vida , Tirosina/sangre , Adulto Joven
3.
Adv Exp Med Biol ; 959: 111-122, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28755189

RESUMEN

Clinically, Hereditary Tyrosinemia type I (HTI) is especially characterized by severe liver dysfunction in early life. However, recurrent neurological crises are another main finding in these patients when they are treated with a tyrosine and phenylalanine restricted diet only. This is caused by the accumulation of δ-aminolevulinic acid due to the inhibitory effect of succinylacetone on the enzyme that metabolizes δ-aminolevulinic acid. Due to the biochemical and clinical resemblance of these neurological crises and acute intermittent porphyria, this group of symptoms in HTI patients is mostly called porphyria-like-syndrome. The neurological crises in HTI patients disappeared after the introduction of treatment with 2-(2 nitro-4-3 trifluoro-methylbenzoyl)-1, 3-cyclohexanedione (NTBC). However, if NTBC treatment is stopped for a while, severe neurological dysfunction will reappear.If NTBC treatment is started early and given continuously, all clinical problems seem to be solved. However, recent research findings indicate that HTI patients have a non-optimal neurocognitive outcome, showing (among others) a lower IQ and impaired executive functioning and social cognition. Unfortunately the exact neuropsychological profile of these HTI patients is not known yet, neither are the exact pathophysiological mechanisms underlying these impairments. It may be hypothesized that the biochemical changes such as high blood tyrosine or low blood phenylalanine concentrations are important in this respect, but an direct toxic effect of NTBC or production of toxic metabolites (that previously characterized the disease before introduction of NTBC) cannot be excluded either. This chapter discusses the neurological and neuropsychological symptoms associated with HTI in detail. An extended section on possible underlying pathophysiological mechanisms of such symptoms is also included.


Asunto(s)
Enfermedades del Sistema Nervioso/etiología , Enfermedades del Sistema Nervioso/patología , Tirosinemias/complicaciones , Tirosinemias/patología , Ciclohexanonas/uso terapéutico , Humanos , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Enfermedades del Sistema Nervioso/metabolismo , Nitrobenzoatos/uso terapéutico , Fenilalanina/metabolismo , Tirosina/metabolismo , Tirosinemias/tratamiento farmacológico , Tirosinemias/metabolismo
4.
Orphanet J Rare Dis ; 11(1): 87, 2016 06 29.
Artículo en Inglés | MEDLINE | ID: mdl-27356512

RESUMEN

BACKGROUND: Hereditary Tyrosinemia type 1 (HT1) is a rare metabolic disorder caused by a defect in the enzyme Fumarylacetoacetate Hydrolase. Due to this defect, toxic products accumulate which, in turn, cause liver and kidney dysfunction. Treatment with 2-(2-nitro-4-trifluoromethylbenoyl)-1,3-cyclohexanedione (NTBC) and diet has diminished these problems, but recent data indicate that HT1 patients have neurocognitive problems. However, the neuropsychological profile of these patients is unknown. Therefore, this study aimed to investigate this neuropsychological profile by comparing HT1 patients with healthy controls. METHODS: Neurocognitive testing was performed in a heterogeneous group of 19 NTBC and dietary treated HT1 patients (five female, fourteen male; mean age 12.9 ± 4.8 years; range 7.9-23.6 years) and 19 age and gender matched controls (five female, fourteen male; mean age 13.2 ± 4.6 years; range 8.1-24.8 years). IQ scores were estimated and all participants performed the Amsterdam Neuropsychological Tasks, measuring executive functions (inhibition, cognitive flexibility and working memory) and social cognition (face recognition and identification of facial emotions). RESULTS: HT1 patients showed poorer estimated IQ, executive functioning (working memory and cognitive flexibility), and social cognition compared to healthy controls. Lower IQ scores in HT1 patients were mostly unrelated to scores on executive function- and social cognition tasks and therefore did not account for group differences in these domains. Further analyses within the HT1 patient group (comparing different groups of patients based on the age at diagnosis and the clinical symptoms at diagnosis) did not reveal any significant results. The duration of NTBC treatment was negatively correlated with IQ. CONCLUSIONS: Despite the heterogeneity of the patient group, these data clearly show that IQ, executive functioning and social cognition are affected in HT1 patients, and that IQ screening is not sufficient for cognitive monitoring of these patients. Further research should focus on the underlying pathophysiological mechanisms of these impairments to consequently try to improve treatment strategies.


Asunto(s)
Tirosinemias/fisiopatología , Adolescente , Adulto , Niño , Cognición/fisiología , Femenino , Humanos , Masculino , Memoria a Corto Plazo/fisiología , Pruebas Neuropsicológicas , Adulto Joven
5.
Dev Med Child Neurol ; 52(7): 620-5, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20187875

RESUMEN

AIM: To examine social information processing in children and adolescents with neurofibromatosis type 1 (NF1). METHOD: Thirty-two children with NF1 (12 males, 20 females; mean age 12y 4mo, SD 4y) and 32 comparison children (12 males, 20 females; mean age 13y 1mo, SD 3y 11mo) completed face recognition, identification of facial emotions (IFE), and matching facial emotions (MFE) tasks. A series of general linear model analyses of variance were used to compare performance between children with NF1 and comparison children. RESULTS: Children with NF1 performed less accurately than comparison children in the face recognition task when faces were presented 'in profile' (p=0.05), when fearful expressions had to be identified in IFE (p=0.017), and across conditions in MFE (p=0.009). When quality of cognitive control (i.e. mean standardized scores on tasks measuring working memory and inhibitory control) was introduced to the analyses, differences in face recognition were no longer significant and differences in MFE were largely reduced (p=0.048). Differences in IFE between the comparison group and children with NF1 remained largely intact (fear: p=0.047). INTERPRETATION: Children with NF1 have problems in social information processing, which, in part, appear to be caused by cognitive control deficits. Some of the deficits, however, appear to be caused by deficient bottom-up processing of social signals (e.g. fear recognition).


Asunto(s)
Emociones , Expresión Facial , Neurofibromatosis 1/psicología , Percepción Social , Adolescente , Niño , Cara , Femenino , Humanos , Modelos Lineales , Masculino , Pruebas Neuropsicológicas , Reconocimiento Visual de Modelos , Tiempo de Reacción , Reconocimiento en Psicología
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