ABSTRACT
La fenilcetonuria, también conocida como PKU, es el error congénito más frecuente del metabolismo de los aminoácidos. La forma grave o PKU clásica no tratada, causa una discapacidad intelectual, aunque los programas de detección en el período neonatal, el diagnóstico y el tratamiento evitan la aparición de los síntomas. A pesar de un diagnóstico y tratamiento temprano hemos observado cierta neurotoxicidad en los pacientes con PKU tratados. Analizamos los demás factores implicados, aparte de la toxicidad por las elevadas concentraciones cerebrales de fenilalanina (Phe), se revisan los defectos de síntesis de neurotransmisores, las alteración de la mielinización cerebral, el efecto de la elevación de Phe en los procesos de transporte y distribución de los aminoácidos neutros con una síntesis anómala de proteínas cerebrales, la deficiencia plasmática y cerebral de tirosina, la neurotoxicidad de los metabolitos de Phe, el defecto de la biosíntesis del colesterol o el aumento del estrés oxidativo. Las alteraciones de la sustancia blanca en los pacientes con PKU tienen un papel importante en las manifestaciones neurológicas. El tratamiento de la PKU es para toda la vida y se basa en la reducción del aporte de alimentos que contienen Phe combinado con la administración de una fórmula especial, o en el tratamiento con tetrahidrobiopterina (BH4). Se analizan nuevas opciones terapéuticas.
Phenylketonuria, also known as PKU, is the most frequent congenital inborn error of metabolism. The severe form or classic PKU untreated causes intellectual disability, although with the early detection programs in the neonatal period, diagnosis and treatment prevent the appearance of the symptoms. Despite early diagnosis and treatment we have observed some neurotoxicity in treated PKU patients. We analyzed the factors involved apart from the toxicity due to the high cerebral concentrations of phenylalanine (Phe), the defects of synthesis of neurotransmitters, the alteration of cerebral myelination, the effect of the elevation of Phe in the processes of transport and distribution of neutral amino acids with an abnormal synthesis of brain proteins, plasma and cerebral tyrosine deficiency, the neurotoxicity of Phe metabolites, the defect of cholesterol biosynthesis or the increase of oxidative stress. White matter alterations in early treated PKU patients have an important role in neurological manifestations. The treatment of PKU is for life and is based on the reduction of foods containing Phe combined with the administration of a special formula or tetrahydrobiopterin (BH4) treatment. New therapeutic options will be analyzed.
Subject(s)
Humans , Phenylalanine/adverse effects , Phenylketonurias/diagnosis , Phenylketonurias/therapy , Tyrosine/metabolism , Neurons/pathology , Phenylketonurias/physiopathology , Biopterin/analogs & derivatives , Early Diagnosis , Diet TherapyABSTRACT
Objective: To systematize a route for the development of recipes with reduced phenylalanine and nutritional and sensory quality. Methods: A systematization of steps for the development of recipes was carried out based on the concepts of dietetics and cooking techniques, besides the pertinent literature. The development of recipes, performed in the laboratory, followed the steps of (1) definition of the objective ofeach culinary preparation; (2) choice of existing recipes that serve as starting points; (3) research of the ingredients allowed in the treatment of phenylketonuria, targeted at technological properties for replacement of eggs, milk and wheat flour; and (4) development and adaption of recipes with standardization of household measures. A nutritional analysis of the preparations was realized based on food composition tables; sensory acceptance tests were also conducted. Results: The preparationswere appropriate for phenylketonuria patients? consumption, because the average phenylalanine value found in each portion was 22.08mg and the scores obtained in the sensory tests were positive. The recipes were developed with ingredients such as fruits and vegetables and were low in fat, which contributed to the nutritional quality of the preparations. Conclusions: The systematization proposed favors the developmentof recipes for phenylketonuria patients with sensory and nutritional quality
Objetivo: Sistematizar um percurso para o desenvolvimento de receitas com redução de fenilalanina e com qualidade nutricional e sensorial. Métodos: Foi realizada sistematização das etapas para o desenvolvimento das receitas, com base nos conceitos da técnica dietética e da gastronomia, além da literatura pertinente. O desenvolvimento das receitas, realizado em laboratório, seguiu as etapas de (1) definição do objetivo decada preparação culinária; (2) escolha de receitas existentes que serviriam de ponto de partida; (3) pesquisa de ingredientes permitidos no tratamento da fenilcetonúria e com propriedades tecnológicas voltadas para a substituição de ovos, leite e farinha de trigo, e (4) desenvolvimento e adequação das receitas com padronização das medidas caseiras. A análise nutricional das preparações foi realizada a partir de tabelas de composição dos alimentos e, além disso, foram realizados testes sensoriais de aceitação. Resultados: As preparações apresentaram-se adequadas para consumo de pacientes fenilcetonúricos, uma vez que o valor médio de fenilalanina encontrado nas porções foi de 22,08mg e os escores alcançados nos testes sensoriais foram positivos. As receitas foram desenvolvidas com ingredientes, como frutas e vegetais, e com baixos teores de gordura, que contribuíram para a qualidade nutricional das preparações. Conclusões: A sistematização proposta favoreceu o desenvolvimento de receitas para fenilcetonúricos com qualidade sensorial e nutricional.
Subject(s)
Cooking/classification , Phenylketonurias/physiopathology , Diet, Protein-Restricted/instrumentationABSTRACT
TEMA: desempenho de crianças com PKU no Teste de Screening de Desenvolvimento Denver - II. Introdução: a fenilcetonúria é uma desordem autossômica recessiva resultante da mutação do gene localizado no cromossomo 12q22.24.1. OBJETIVO: caracterizar o desempenho de crianças com fenilcetonúria diagnosticadas e tratadas precocemente por meio do Teste de Screening de Desenvolvimento Denver II e dos níveis de fenilalanina sanguíneos. MÉTODO: participaram 20 crianças, dez com fenilcetonúria, diagnosticadas e tratadas desde o nascimento, de idade cronológica entre três a seis anos, e dez crianças do grupo típico, pareadas quanto ao sexo, idade e nível socioeconômico. Os níveis sanguíneos e as informações neurológicas, psicológicas e sociais foram obtidas no banco de dados do Programa de Triagem Neonatal para Erros Inatos do Metabolismo. A avaliação constou da aplicação do Teste de Screening de Desenvolvimento Denver-II. Utilizou-se estatística descritiva e aplicação do teste estatístico de Mann Whitney para a caracterização das habilidades. Para as medições dos níveis plasmáticos sanguíneos de fenilalanina considerou-se os valores abaixo de 2mg/dL, acima de 4mg/dL, os valores de referência entre 2 e 4mg/dL, de todos os exames realizados no decorrer da vida dos participantes, os valores mínimos e máximos e o valor obtido na época da avaliação fonoaudiológica. Resultado: A comparação entre os grupos foi estatisticamente significante nas áreas pessoal-social e de linguagem. CONCLUSÃO: crianças com fenilcetonúria diagnosticadas e tratadas precocemente apresentaram prejuízo nas áreas pessoal-social e de linguagem e, mesmo com o acompanhamento periódico, apresentaram dificuldades para manter os níveis de normalidade de fenilalanina, embora realizassem o tratamento recomendado.
BACKGROUND: phenylketonuria is an autosomal recessive disorder resulting from the mutation of a gene located in chromosome 12q22-24.1. AIM: to describe the performance of children with classic phenylketonuria, who were diagnosed and treated early, in the Development Screening Test Denver - II. METHOD: participants were 20 children with phenylketonuria, ranging in age from 3 and 6 years, and 10 children with typical language development, paired by gender, age and socioeconomic level to the research group. The plasmatic phenylalanine measure and the neurological, psychological and social information were gathered in the data base of the Neonatal Screening Programs for Metabolic disorder. Assessment consisted on the application of the Development Screening Test Denver II. A descriptive statistical analysis and the Mann Whitney test were used in order to characterize the tested skills. For the measurements of the plasmatic phenylalanine blood levels the values considered for analysis were: below 2mg/dL, above 4mg/dL, reference values between 2 and 4mg/dL, of all exams performed during the participants'lives; maximum and minimum values and values obtained on the day of the screening application. RESULTS: comparison between the groups indicated statistically significant differences for the personal-social and language areas. CONCLUSION:children who were diagnosed and treated early for phenylketonuria present deficits in the personal-social and language areas. Also, even when receiving follow-up and undergoing treatment, these children presented difficulties in maintaining normal plasmatic phenylalanine levels.
Subject(s)
Child , Child, Preschool , Female , Humans , Male , Developmental Disabilities/diagnosis , Phenylalanine/blood , Phenylketonurias/physiopathology , Biomarkers/blood , Case-Control Studies , Early Diagnosis , Phenylketonurias/diagnosis , Phenylketonurias/therapy , Reference Values , Statistics, NonparametricABSTRACT
The Neonatal Screening for Inborn Errors of Metabolism of the Association of Parents and Friends of Special Needs Individuals (APAE) - Bauru, Brazil, was implanted and accredited by the Brazilian Ministry of Health in 1998. It covers about 286 cities of the Bauru region and 420 collection spots. Their activities include screening, diagnosis, treatment and assistance to congenital hypothyroidism (CH) and phenylketonuria (PKU), among others. In 2005, a partnership was established with the Department of Speech-Language Pathology and Audiology, Bauru School of Dentistry, University of São Paulo, Bauru, seeking to characterize and to follow, by means of research studies, the development of the communicative abilities of children with CH and PKU. OBJECTIVE: The aim of this study was to describe communicative and psycholinguistic abilities in children with CH and PKU. MATERIALS AND METHODS: Sixty-eight children (25 children aged 1 to 120 months with PKU and 43 children aged 1 to 60 months with CH) participated in the study. The handbooks were analyzed and different instruments were applied (Observation of Communication Behavior, Early Language Milestone Scale, Peabody Picture Vocabulary Test, Gesell & Amatruda's Behavioral Development Scale, Portage Operation Inventory, Language Development Evaluation Scale, Denver Developmental Screening Test, ABFW Child Language Test-phonology and Illinois Test of Psycholinguistic Abilities), according to the children's age group and developmental level. RESULTS: It was observed that the children with PKU and CH at risk for alterations in their developmental abilities (motor, cognitive, linguistic, adaptive and personal-social), mainly in the first years of life. Alterations in the psycholinguistic abilities were also found, mainly after the preschool age. Attention deficits, language and cognitive alterations were more often observed in children with CH, while attention deficits with hyperactivity and alterations in the personal-social, language and motor adaptive abilities were more frequent in children with PKU. CONCLUSION: CH and PKU can cause communicative and psycholinguistic alterations that compromise the communication and affect the social integration and learning of these individuals, proving the need of having these abilities assisted by a speech and language pathologist.
Subject(s)
Child , Child, Preschool , Female , Humans , Infant , Male , Communication , Congenital Hypothyroidism/physiopathology , Language Development , Phenylketonurias/physiopathology , Brazil , Cognition , Language Tests , Psycholinguistics , Psychomotor Performance/physiology , Statistics, NonparametricABSTRACT
Este estudo investiga a hipótese de um déficit específico das funções executivas em crianças com fenilcetonúria (PKU) cujo nível de fenilalanina encontra-se entre 360 e 600 mmol/l. Participaram do estudo 21 crianças fenilcetonúricas de nove meses de idade, tratadas precoce e continuamente, e 18 crianças normais de mesma idade. As crianças com PKU foram divididas em dois grupos em função do nível médio de fenilalanina antes do estudo: o grupo de crianças cujo nível encontrava-se entre 120 e 360 mmol/l e o grupo de crianças cujo nível encontrava-se entre 360 e 600 mmol/l. Embora os três grupos de crianças tenham apresentado desempenho semelhante em um teste que avalia o desenvolvimento mental global, as crianças com alto nível de fenilalanina apresentaram desempenho significativamente pior do que as demais crianças em um teste que avalia as funções executivas.
Subject(s)
Humans , Male , Female , Child , Behavior , Psychomotor Performance , Phenylalanine/analysis , Phenylketonurias/physiopathology , Attention , MemoryABSTRACT
La fenilcetonuria es un error innato del metabolismo transmitido por un gen autosómico recesivo, que consiste en un defecto enzimático de hidroxilación de fenilalanina, con producción de metabolitos nocivos para el desarrollo del sistema nervioso central, y consecuente deficiencia mental. La importancia fundamental de la fenilcetonuria es que por medio de su diagnóstico y tratamiento precoz, se está haciendo prevención de deficiencia mental grave, factor de gran valor en los países en vías de desarrollo, donde la incidencia de deficiencia mental tiene tasas tan elevadas (3-5% pudiendo llegar a 7-10%). En América Latina, donde no existe cobertura completa de todos los recién nacidos para detección precoz de los niveles de fenilalanina sanguínea, se tiene alta frecuencia de casos diagnosticados tardíamente, ya con deficiencia mental. Teniéndose presente la importancia del diagnóstico precoz es imprescindible la realización del test de selección poblacional y que la atención del pediatra estuviera volcada para esta patología, que tiene una incidencia de 1: 12.000 - 1: 15.000 (Ciudad de San Pablo)