Neuropsychological and quality of life outcomes in PKU patients: expert recommendations of assessment tools in Brazil / Desfechos neuropsicológicos e de qualidade de vida em pacientes com PKU: recomendações de especialistas sobre ferramentas de avaliação no Brasil

Abstract Background Phenylketonuria (PKU) is an inborn error of metabolism caused by deficient activity of phenylalanine hydroxylase. In Brazil, the National Neonatal Screening Program enables early treatment of patients with PKU, which prevents them from developing severe neurological damage and mental disabilities. However, between 20 and 30% of early-treated patients with PKU present focal cognitive deficits, including deficits in working memory, processing speed, and psychiatric symptoms such as anxiety, depression, and attention deficit hyperactivity disorder (ADHD). Therefore, age-specific neuropsychiatric and cognitive tests are important components of PKU patient care. To date, there are no officially approved guidelines or recommendations of tools in Portuguese validated for use in Brazil that could be applied to assess these parameters in patients with PKU. Objective To recommend tools validated for use in Brazil that can be used in daily clinical practice to assess quality of life and neuropsychological outcomes in patients with PKU. Methods Six Brazilian experts discussed about eligible tools based on their clinical experience, the feasibility of their use in clinical routines, and their availability in public health services. Before the meeting, an independent review of the literature was conducted to identify the currently validated tools in Brazil, using the MEDLINE and SciELO databases. Results The experts recommended nine tools to assess quality of life (Peds-QL, SF-36 or WHOQOL-bref), executive function (BRIEF or Bayley-III), IQ (SONR 2½-7[a] or WASI) and ADHD (MTA-SNAP-IV and ASRS). Conclusions These instruments may be easily incorporated into clinical practice and improve the quality of multidisciplinary care of patients with PKU.

Resumo Antecedentes A fenilcetonúria (PKU) é um erro inato do metabolismo causado pela atividade deficiente da fenilalanina hidroxilase. No Brasil, o Programa Nacional de Triagem Neonatal permite o tratamento precoce de pacientes com PKU, o que os impede de desenvolver danos neurológicos e deficiências intelectuais graves. No entanto, já foi descrito que de 20 a 30% dos pacientes tratados precocemente com PKU apresentam déficits cognitivos focais, incluindo déficits na memória de trabalho, velocidade de processamento e sintomas psiquiátricos como ansiedade, depressão e Transtorno de Déficit de Atenção e Hiperatividade (TDAH). Neste sentido, testes neuropsiquiátricos e cognitivos são componentes importantes no cuidado destes pacientes. Atualmente, não existe um compêndio científico ou recomendações de ferramentas validadas em português para avaliar a saúde mental em pacientes brasileiros com PKU. Objetivo Recomendar ferramentas validadas localmente para avaliar a qualidade de vida e aspectos neuropsicológicos de pacientes com PKU. Métodos Seis especialistas brasileiros discutiram as ferramentas mais apropriadas com base em suas experiências clínicas, a viabilidade de realizar as avaliações na rotina clínica, e o acesso às ferramentas na saúde pública. Antes da reunião, foi realizada uma revisão independente da literatura para identificar as ferramentas validadas no Brasil, utilizando as bases de dados MEDLINE e Scielo. Resultados Os especialistas recomendaram nove ferramentas para avaliar a qualidade de vida (Peds-QL, SF-36 ou WHOQOL-bref), função executiva (BRIEF ou Bayley-III), QI (SONR 2½-7[a] ou WASI) e TDAH (MTA-SNAP-IV e ASRS). Conclusões Estes instrumentos podem ser facilmente incorporados na prática clínica e melhorar a qualidade dos cuidados multidisciplinares dos pacientes com PKU.

Dificuldades alimentares em pacientes com Fenilcetonúria / Feeding difficulties in patients with Phenylketonuria

RESUMO Objetivo analisar os resultados de um instrumento que se propõe a auxiliar na identificação das dificuldades alimentares em crianças com Fenilcetonúria (PKU), em comparação a crianças sem a doença. Método estudo transversal, controlado, com amostra de conveniência composta por pacientes com PKU e por indivíduos hígidos, equiparados por idade e sexo. O convite para participação no estudo foi feito por meio de divulgação da pesquisa nas redes sociais. As respostas foram fornecidas pelos responsáveis, sendo que 46 controles e 28 pacientes participaram. Além desses, 13 responsáveis por pacientes em acompanhamento em um Ambulatório de Tratamento de Erros Inatos do Metabolismo foram convidados por ligação telefônica, sendo que 12 aceitaram o convite. Todos os participantes responderam a Escala Brasileira de Alimentação Infantil (EBAI) de forma eletrônica. Resultados foram incluídos no estudo 86 participantes, sendo 40 pacientes (mediana de idade, 2 anos; intervalo interquartil (IQR) = 2 - 4) e 46 controles (mediana de idade, 3,5 anos; IQR = 2 - 5,25). Dez (25%) pacientes e 13 (28,3%) controles apresentaram resultados compatíveis com dificuldades alimentares, demonstrando uma frequência semelhante entre os grupos. O estudo observou que os pacientes com PKU apresentaram menos autonomia alimentar (p = 0,005), foram menos amamentados (p = 0,002) e usaram mais mamadeira que os controles (p = 0,028). Conclusão a frequência de dificuldades alimentares referidas pelos cuidadores foi semelhante entre os grupos, porém as crianças com PKU demonstraram menos autonomia para se alimentar, foram menos amamentadas e usaram mais mamadeira quando comparadas com as crianças sem a doença.

ABSTRACT Purpose to analyze the results of an instrument that aims to assist in the identification of feeding difficulties in children with Phenylketonuria (PKU), compared to children without the disease. Methods cross-sectional, controlled study with a convenience sample composed of patients with PKU and healthy individuals, matched for age and sex. The invitation to participate in the study was made through the dissemination of the research on social networks. The answers were provided by the guardians, 46 controls and 28 patients agreed to participate. In addition to these, 13 guardians of patients being followed up at an Outpatient Clinic for the Treatment of Inborn Errors of Metabolism were invited by phone call, and 12 accepted the invitation. All participants answered the Brazilian Infant Feeding Scale (in Portuguese Escala Brasileira de Alimentação Infantil (EBAI)) electronically. Results the study included 86 participants, 40 patients (median of age = 2 years; interquartile range (IQR) = 2 - 4) and 46 controls (median of age = 3.5 years; IQR = 2 - 5.25). Ten (25%) patients and 13 (28.3%) controls had suspicion of feeding difficulties, demonstrating a similar frequency of feeding difficulties between groups. The study found that PKU patients had less feed autonomy (p = 0.005), were less breastfed (p = 0.002) and used more baby's bottle than controls (p = 0.028). Conclusion the frequency of feeding difficulties reported by caregivers was similar between the comparison groups, but children with PKU had less feed autonomy, were less breastfed and used more baby's bottles when compared to children without the disease.

Brazilian Food Reference Guide for Phenylalanine Content: A Study Based on the Perception of PKU Patients and Health Providers

Abstract The mainstay of management of phenylketonuria (PKU) is restriction of dietary phenylalanine (Phe) intake. The present study sought to assess the perception and understanding of health care providers and lay users (patients/family members/caregivers) regarding the national reference database for checking the Phe content of foods, provided by the Brazilian Health Regulatory Agency (Anvisa), whose data are presented in the Table of Phenylalanine Content of Foods (TCFA-Anvisa) and recently in the Phenylalanine Content of Foods Dashboard (PCCFA-Anvisa); and to identify factors which interfere with the usability of these resources. Two online questionnaires, one for providers (n=33) and another for lay users (n=194), were used to collect sociodemographic information, knowledge about dietary management of PKU, sources of information about the Phe content of foods, and perception and understanding of the Anvisa tools. TCFA-Anvisa and PCCFA-Anvisa were not used as main sources of information by either group. Among the participants who had used these tools (15 providers;35 lay users), most considered the PCCFA-Anvisa to be superior or partially superior to the TCFA-Anvisa. The main limitations reported were related to layout and limited variety of foods. We suggest that the limitations identified in this study be considered for future improvement of these resources.

Metabolic control and body composition of children and adolescents with phenylketonuria / Controle metabólico e composição corporal de crianças e adolescentes com diagnóstico neonatal de fenilcetonúria

ABSTRACT Objective: To characterize metabolic control and verify whether it has any relation with socioeconomic, demographic, and body composition variables in children and adolescents with phenylketonuria (PKU) diagnosed in the neonatal period. Methods: This cohort study collected retrospective data of 53 phenylketonuric children and adolescents. Data on family income, housing, and mother's age and schooling level were collected, and anthropometric measures of body composition and distribution were taken. All dosages of phenylalanine (Phe) from the last five years (2015-2019) were evaluated and classified regarding their adequacy (cutoffs: 0-12 years: 2-6 mg/dL; 12-19 years: 2-10 mg/dL). Adequate metabolic control was considered if ≥7%) of the dosages were within desired ranges. Results: The mean (±standard deviation) age in the last year was 10.1±4.6 years. Most of them were under 12 years old (33/53; 62.3%) and had the classic form of the disease (39/53; 73.6%). Better metabolic control was observed among adolescents (68.4 versus 51.4%; p=0.019). Overweight was found in 9/53 (17%) and higher serum Phe levels (p<0.001) were found in this group of patients. Metabolic control with 70% or more Phe level adequacy decreased along with the arm muscle area (AMA) (ptendency=0.042), being 70.0% among those with low reserve (low AMA), and 18.5% among those with excessive reserve (high AMA). Conclusions: Adequate metabolic control was observed in most patients. The findings suggest that, in this sample, the levels of phenylalanine may be related to changes in body composition.

RESUMO Objetivo: Caracterizar o controle metabólico e verificar se existe relação entre ele, variáveis socioeconômicas, demográficas e composição corporal de crianças e adolescentes com fenilcetonúria (FNC) diagnosticada no período neonatal. Métodos: Coorte com coleta retrospectiva de dados de 53 crianças e adolescentes fenilcetonúricos. Foram coletados dados de renda familiar, moradia, idade e escolaridade materna e realizaram-se medidas antropométricas de composição e distribuição corporal. Todas as dosagens de fenilalanina (Fal) dos últimos cinco anos (2015-2019) foram avaliadas e classificadas quanto à adequação (cortes: 0-12 anos: 2-6 mg/dL; 12-19 anos: 2-10 mg/dL). A proporção de dosagens adequadas ≥70% foi considerada como controle metabólico adequado. Resultados: A média (±desvio padrão) de idade, no último ano, foi de 10,1±4,6 anos. A maioria tinha menos de 12 anos (33/53; 62,3%) e apresentava a forma clássica da doença (39/53; 73,6%). Observou-se melhor controle metabólico entre os adolescentes (68,4 vs. 51,4%; p=0,019). Excesso de peso foi encontrado em 9/53 (17%) e maiores níveis séricos de Fal foram descritos nesse grupo (p<0,001). O percentual de controle metabólico com 70% ou mais de adequação dos níveis de Fal foi decrescente de acordo com a área muscular do braço (AMB; ptendência=0,042), sendo de 70% entre os de baixa reserva (AMB reduzida) e de 18,5% entre os com excesso (AMB elevada). Conclusões: Observou-se controle metabólico adequado na maioria dos avaliados e os achados sugerem que, nesta amostra, os níveis de fenilalanina podem estar relacionados com alterações da composição corporal.

Sobrepeso/obesidade e doença hepática gordurosa não alcoólica em adolescentes com fenilcetonúria / Overweight/obesity and non alcoholic fat liver disease in adolescents with phenylketonuria

Introdução: A fenilcetonúria (PKU) é um erro inato do metabolismo, devido à perda ou diminuição da atividade da enzima fenilalanina hidroxilase. A dieta, com restrição de proteínas naturais e uso de fórmula de aminoácidos isenta em fenilalanina tem papel chave em seu tratamento. As peculiaridades da dieta têm levado à hipótese de predisposição ao sobrepeso/obesidade que, por outro lado é suspeito de predispor à doença hepática gordurosa não alcoólica (DHGNA). Teriam adolescentes com PKU maior predisposição ao desenvolvimento de sobrepeso/obesidade e à DHGNA? Objetivo: Avaliar sobrepeso/obesidade e DHGNA em adolescentes com PKU em tratamento dietético exclusivo. Métodos: Estudo transversal com 101 adolescentes com PKU entre 10 anos e 20 anos incompletos entre 2017-2018. Foram realizadas avaliações antropométricas, bioquímicas, determinação do consumo alimentar e ultrassom abdominal, com classificação do índice hepatorenal. Os pacientes foram divididos em dois grupos, de acordo com seu estado nutricional: um com os indivíduos com sobrepeso/obesidade, outro com eutrofia/baixo IMC. Foi constituído subgrupo com adolescentes de 13-17 anos para comparação com prevalência do sobrepeso/obesidade em escolares sadios, da mesma idade. Resultados: A prevalência de sobrepeso/obesidade foi de 27,7% e não houve predominância de sexos. A análise multivariada indicou concentrações sanguíneas elevadas de fenilalanina, de LDL-colesterol e elevação do índice HOMA como fatores preditores e aumento da idade como fator protetor do sobrepeso/obesidade. A comparação da prevalência de sobrepeso/obesidade entre os 46 pacientes entre 13-17 anos com escolares da mesma idade não rejeitou a hipótese de igualdade. A avaliação do índice hepatorenal detectou presença de DHGNA em 26 (25,7%) adolescentes, sem distinção entre sexos ou associação com sobrepeso/obesidade, sugerindo que a PKU e/ou a dieta podem contribuir para a DHGNA. O modelo final da análise multivariada, apresentou sensibilidade de 26,1% e especificidade de 94,7%, indicando a necessidade de estudar outras variáveis. A especificidade do modelo final sugeriu uma possibilidade menor de DHGNA naqueles com idade maior, níveis de fosfatase alcalina normal ou elevada, menor consumo de carboidratos e lipídios e consumo adequado de proteínas. Conclusão: A prevalência de sobrepeso/obesidade dos adolescentes com PKU foi semelhante à encontrada entre os adolescentes sem a doença. Concentrações elevadas de Phe, e LDL colesterol e índice HOMA acima da referência foram fatores preditores da mesma e idade mais elevada fator protetor. A PKU e/ou a dieta utilizada em seu tratamento podem representar risco de DHGNA, independentemente do sexo e do estado nutricional. A especificidade do modelo final sugeriu a possibilidade de DHGNA menor naqueles com idade maior, níveis de fosfatase alcalina normal/elevada, menor consumo de carboidratos e lipídios e consumo adequado de proteínas.

Overweight and associated factors in children and adolescents with phenylketonuria: a systematic review / Excesso de peso e fatores associados em crianças e adolescentes com fenilcetonúria: uma revisão sistemática

ABSTRACT Objective: To verify the occurrence of overweight in children and adolescents with phenylketonuria and to identify possible causal factors. Data sources: A systematic review was performed in the SciELO, PubMed and VHL databases using the descriptors "Phenylketonurias", "Overweight", "Child" and "Adolescent". Original articles conducted with children and adolescents, published between 2008 and 2018 in Portuguese, English or Spanish languages were included. Data synthesis: A total of 16 articles were identified and, after screening procedures, 6 studies were selected for the review. Overweight in children and adolescents with phenylketonuria was a frequent occurence in the studies included in this review, ranging from 7.8 to 32.6%. The female sex was the most affected by the nutritional disorder. Furthermore, a high caloric intake combined with a lack of stimuli to practice physical activities were main factors associated with the excessive weight in the population of interest. Conclusions: Excess weight can be considered a common outcome in children and adolescents with phenylketonuria. It is mainly caused by inadequate food consumption and sedentary lifestyle. The importance of early identification of nutritional disturbances in children and adolescents with phenylketonuria should be emphasized, in order to prevent associated chronic diseases and to promote health by encouraging continued healthy eating habits and the regular practice of physical exercises.

RESUMO Objetivo: Verificar a ocorrência de excesso de peso em crianças e adolescentes com fenilcetonúria e identificar possíveis fatores causais. Fontes de dados: Revisão sistemática realizada nas bases de dados Scientific Eletronic Library Online (SciELO), Publisher Medline (PubMed) e Biblioteca Virtual em Saúde (BVS) com os descritores "Phenylketonurias", "Overweight", "Child" e "Adolescent". Foram incluídos artigos originais sobre crianças e adolescentes, publicados entre 2008 e 2018 nos idiomas português, inglês ou espanhol. Síntese dos dados: Foram identificados 16 artigos e, após aplicação dos procedimentos de seleção, 6 estudos foram selecionados para compor a revisão. O excesso de peso em crianças e adolescentes com fenilcetonúria foi evento frequente nos estudos incluídos na presente revisão, variando de 7,8 a 32,6%. Aponta-se o sexo feminino como o grupo mais acometido pelo distúrbio nutricional. O principal fator associado ao excesso de peso na população de interesse na população de interesse foi o consumo calórico elevado aliado à falta de estímulos para a prática de atividades físicas. Conclusões: O excesso de peso pode ser considerado um desfecho comum em crianças e adolescentes com fenilcetonúria, sendo ocasionado principalmente pelo consumo alimentar inadequado e pelo sedentarismo. Salienta-se a importância da identificação precoce de agravos nutricionais em crianças e adolescentes fenilcetonúricos, a fim de prevenir doenças crônicas associadas e promover a saúde, com incentivo à manutenção de hábitos alimentares saudáveis e à prática regular de exercícios físicos.

Comparison of different methods for measuring the phenylalanine concentration of phenylketonuria patients in dried blood spots / 中华检验医学杂志

Objective To compare the phenylalanine(Phe)concentration in the sample of dried blood spot,measured by four different methods:fluorescence assay,tandem mass spectrometry(MS/MS), including MS/MS Derivatized,MS/MS Non-Derivatized and MS/MS-Standard Curve.Methods A total of 204 dried blood spot(DBS)samples of phenylketonuria(PKU)patients from Shanghai Xinhua Hospital were collected in this study.Phe concentration in DBS was measured by fluorescence assay and MS /MS assay,including MS/MS Derivatized, MS/MS Non-Derivatized and MS/MS-Standard Curve.The samples were divided into low, middle and high concentration groups according to Phe concentration, which were under the 360 μmol/L,between 360 and 600 μmol/L,and over 600 μmol/L respectively.The differences among the groups were analyzed by consistency check and non-parametric test.Results The within-day and between-day precisions of MS/MS-Standard Curve assay were 4.0%-7.2%,the recoveries were 93.2%-97.3%.Consistency check showed that less than 8.1%of Phe value were out of the 95%limit of agreement among these four methods.In the low and middle concentration groups,the quartile of Phe value measured by fluorescence assay,MS/MS Standard Curve and MS/MS Derivatized were 176(118,251)μmol/L,174 (94,273)μmol/L,153(94,242)μmol/L; and 540(478,578)μmol/L,485(414,529)μmol/L,466(402,513)μmol/L,respectively.Phe value measured by fluorescence assay was significantly higher than that by MS/MS Standard Curve,the difference was 4.8%-9.0%,(Z=-3.787 to -2.674,P<0.01). Phe value obtained from MS/MS Non-Derivatized was less than that by MS/MS-Standard Curve, the difference was 3.9%-5.2%,(Z=-7.474 to -5.747,P<0.01).In the high concentration group,the quartile of Phe value measured by MS/MS-Standard Curve, MS/MS Derivatized, MS/MS Non-Derivatized and fluorescence assay were 807(695,924)μmol/L,700(575,785)μmol/L,680(623,771)μmol/L and 711(674, 794)μmol/L, respectively.Phe value obtained from MS/MS Standard Curve was significantly higher than those from the other methods and the difference was 10.9% -16.2%,(Z=-4.458 to-4.356,P<0.01).Conclusions The MS/MS Standard Curve assay showed good specificity and accuracy.These four assays displayed good agreement.Although there was difference in measuring the Phe concentration among these methods, they could be used in blood Phe concentration monitoring for PKU patients.

Prenatal diagnosis and PAH gene mutations in 55 pedigrees with phenylketonuria / 中华围产医学杂志

Objective To investigate phenylalanine hydroxylase ( PA H ) gene mutations and to perform prenatal diagnosis in 55 pedigrees with classical phenylketonuria (PKU). Methods Subjects of this study were 55 probands diagnosed with PKU in the Gansu Provincial Maternal and Child Health Care Hospital from 2013 to 2017 and their pedigrees. Sanger sequencing/Multiplex ligation-dependent probe amplification (MLPA) was used to investigate PA H gene mutations in these probands and their parents. Sanger sequencing/MLPA, linkage analysis of three common short tandem repeats (STR) including PAH-26, PAH-STR and PAH-32 in the PA H gene and paternity testing were used in combination for prenatal diagnosis of 60 fetuses in the 55 pedigrees. Results Among the 110 alleles in the 55 probands, 108 mutant alleles (98.2%) were found by Sanger sequencing. The 108 mutant alleles located in 38 regions resulting in 22 missense mutations, nine splice site mutations, five nonsense mutations and two microdeletion. The most common mutations were c.728G>A (22.2%, 24/108), c.442-1G>A (5.6%, 6/108), c.611A>G (5.6%, 6/108), c.764T>C (5.6%, 6/108), c.1068C>A (5.6%, 6/108) and c.331C>T (4.6%, 5/108). Loss of heterozygosity in 4-5 and 4-7 exons were detected by MLPA in two probands, in which only one mutation was unidentified. Prenatal diagnosis for the 60 fetuses were successfully performed. Among them, 17 fetuses (28.3%) were affected, 29 fetuses (48.3%) were heterozygous carriers and fetuses 14(23.4%) were unaffected ones. Conclusions Combination of Sanger sequencing/MLPA, linkage analysis and paternity testing could provide accurate prenatal diagnosis in pedigrees with PKU.

Outcomes of children with Phenylketonuria detected by newborn screening program / 中华全科医师杂志

Objective To evaluate the outcomes of children with Phenylketonuria(PKU)detected by newborn screening program.Methods One hundred and two children with PKU were detected and diagnosed in Shanxi Newborn Screening Center from June 2004 to September 2014.All children with PKU were followed up until December 2015.During the follow-up,the Phenylalanine(Phe)levels,physical and intellectual development, nutrition status of those children were monitored.Results Among 102 PKU children,there were 96(94.12%)with normal physical development,and 93(91.18%)with normal DQ/IQ.The average DQ or IQ score in children who started the therapy before 1 month was higher than that in those who started after 1 month old(93.07 ±9.50 vs.87.39 ±10.99,t=3.09, P=0.00).Among these children 82.47%(80/97)had zinc deficiency and 31.46%(28/89)had dyslipidemia; and the normal Phe concentration rate was(59.73 ±19.03)%.The intellectual development level was negatively correlated with the age of starting therapy(r=-0.25, P=0.01), positively correlated with the education levels of his/her father(r=0.21,P=0.03)and mother(r=0.23, P=0.02).And the intellectual development was better in urban areas than that in rural areas.Conclusions With the standardized treatment, the physical and intellectual development of children with PKU can basically reach normal levels,and the earlier treatment can make better therapeutic effect.

Fenilcetonúria: aspectos genéticos, diagnóstico e tratamento / Phenylketonuria: genetic aspects, diagnosis and treatment

A fenilcetonúria é uma doença genética e metabólica, com bom prognóstico caso seja detectada e tratada precocemente. É a mais frequente entre os distúrbios metabólicos com significativa implicação clínica. Ela é detectada precocemente pelo Teste do Pezinho na triagem neonatal, e o tratamento padrão consiste em dieta restritiva. Este estudo teve por finalidade informar e atualizar os profissionais da área da saúde sobre base genético-clínica da fenilcetonúria, com destaque para sua etiologia e aconselhamento genético; diagnóstico com enfoque no histórico da triagem neonatal; e tratamento − em especial o dietético. Foi utilizada como fonte a literatura científica especializada, publicada principalmente nos últimos 5 anos.(AU)

Phenylketonuria is a genetic and metabolic disease, with good prognosis if early detected and treated. It is the most frequent among metabolic disorders, with significant clinical implications. It is detected early by Guthrie test in the neonatal screening, and the standard treatment consists of a restrictive diet. This study is aimed at informing and updating healthcare professionals on: 1) genetic-clinical basis of phenylketonuria, highlighting its etiology and genetic counseling, 2) diagnosis focusing on the history of newborn screening, and 3) treatment, in particular the dietetic one. The specialized scientific literature, particularly that published in the last five years, was used as a source.(AU)

Caracterización fenotípica y molecular de una familia colombiana con fenilcetonuria / Phenotypic and molecular characterization of a Colombian family with phenylketonuria

Introducción. La fenilcetonuria es un trastorno metabólico caracterizado por un compromiso neurológico grave y por alteraciones del comportamiento. Su diagnóstico temprano permite establecer un tratamiento efectivo que evita las secuelas y modifica el pronóstico. Objetivo. Caracterizar a una familia con fenilcetonuria en Colombia, a nivel clínico, bioquímico y molecular. Materiales y métodos. Se estudió una población de siete individuos de una familia consanguínea en la que cuatro hijos presentaban signos clínicos sugestivos de fenilcetonuria. Una vez firmado el consentimiento informado, se tomaron muestras de sangre y orina para las pruebas colorimétricas, la cromatografía de capa fina y la cromatografía líquida de alta eficacia. Se extrajo el ADN y se secuenciaron los 13 exones del gen PAH de todos los sujetos estudiados. Se diseñaron iniciadores para cada exón con el programa Primer 3; la secuenciación automática se hizo con el equipo Abiprism 3100 Avant y, el análisis de las secuencias, con el programa SeqScape v2.0. Resultados. Se describieron las características clínicas y moleculares de una familia colombiana con fenilcetonuria en la que se identificó la mutación c.398_401delATCA; se presentó una correlación fenotipo-genotipo con una interesante variabilidad clínica entre los afectados, a pesar de tener la misma mutación. Conclusiones. Es importante el reconocimiento temprano de esta enfermedad para evitar sus secuelas neurológicas y psicológicas, pues los pacientes llegan a edades avanzadas sin diagnóstico ni tratamiento adecuados.

Introduction: Phenylketonuria is a metabolic disorder characterized by severe neurological involvement and behavioral disorder, whose early diagnosis enables an effective treatment to avoid disease sequelae, thus changing the prognosis. Objective: To characterize a family with phenylketonuria in Colombia at clinical, biochemical and molecular levels. Materials and methods: The population consisted of seven individuals of a consanguineous family with four children with suggestive symptoms of phenylketonuria. After signing an informed consent, blood and urine samples were taken for colorimetric tests and high performance liquid and thin layer chromatographies. DNA extraction and sequencing of the 13 exons of the PAH gene were performed in all subjects. We designed primers for each exon with the Primer 3 software using automatic sequencing equipment Abiprism 3100 Avant. Sequences were analyzed using the SeqScape, v2.0, software. Results: We described the clinical and molecular characteristics of a Colombian family with phenylketonuria and confirmed the presence of the mutation c.398_401delATCA. We established a genotype-phenotype correlation, highlighting the interesting clinical variability found among the affected patients despite having the same mutation in all of them. Conclusions: Early recognition of this disease is very important to prevent its neurological and psychological sequelae, given that patients reach old age without diagnosis or proper management.

Analysis of neonatal hyperphenylalaninemia screening and therapeutic effect in Xuzhou from 2003 to 2015 / 中华围产医学杂志

Objective To investigate the prevalence,clinical classification,treatment and prognosis of neonatal hyperphenylalaninemia(HPA) in Xuzhou area,China.Methods Infants born between July 1,2003 and July 1,2015 in Xuzhou area were investigated.Heel blood samples of neonates were collected at 72 hours after birth,and the concentration of blood phenylalanine(Phe) was determined by fluorescent quantitative method in Xuzhou Maternity and Child Health Care Station Neonatal Disease Screening Center.Differential diagnosis was performed in all 265 cases diagnosed as HPA by urinary pterin analysis and dihydropteridine reductase activity determination.The blood Phe concentration and mental development were followed up regularly in infants with HPA.Mutations of phenylalanine hydroxylase (PAH) gene were analyzed by gene sequencing.The relationship between blood Phe concentration and mental development was analyzed by Bivariate correlation analysis.Results (1) The prevalence of HPA in neonates in Xuzhou was 1/4 635.Among the 265 confirmed HPA cases,260 cases(98.11％) had PAH deficiency,including 90(33.96％) classical phenylketonuria(PKU),84(31.70％) mild PKU and 86(32.45％) mild HPA.The other five patients(1.89％) diagnosed with tetrahydrobiopterin (BH4) deficiency all had 6-pyruvoyl tetrahydropteim synthase(PTPS) deficiency.(2) Among the 265 HPA cases,26 cases refused any treatment,including five cases of PTPS deficiency and 21 cases of PKU.Of the five patients with PTPS deficiency,two died and the other three had normal mental and physical development.Twenty-one PKU patients who refused treatment had mental retardation of various degrees.Among 153 PKU patients who received medical treatment,three died and 12 were lost to follow-up.(3) For 138 PKU patients who received dietary treatment and follow-up,the ages at the last visit were two months to 12 years,116 of them had normal mental development,the remaining 22 patients had mental retardation,and a negative correlation was observed between mental development and the average Phe concentration.(4) Thirty-five patients with PAH deficiency underwent gene sequencing,and 22 kinds of mutations of PAH gene were detected.Conclusions The prevalence of HPA in Xuzhou area is higher than the average national level.With early diagnosis and standard treatment,most of PKU neonates can have normal mental development.Phe level control is an important factor for mental development.

PTPS gene analysis and prenatal diagnosis in patients with 6-pyruvoyl-tetra hydropterin synthase deficiency / 中华妇产科杂志

Objective To analyze the variations of PTPS gene in patients with suspected 6-pyruvoyl-tetra hydropterin synthase deficiency (PTPSD) and to make prenatal diagnosis in high-risk families. Methods Chemiluminescence was used for phenylalanine detection in blood or dried blood spots.Patients with phenylalanine concentration over 120μmol/L were detected by urine pterin analysis, and the activity of dihydropteridine reductase (DHPR) was detected. tetrahydrobiopterin loading tests were performed in suspected patients with abnormal urinary pterin profiles. PTPS gene variation analysis was performed by direct Sanger sequencing based on PCR amplification. Prenatal diagnosis in 7 high-risk families was performed by chorionic villus sampling when the genotype was identified. Results In 656 patients with hyperphenylalanine, 22 cases were diagnosed as PTPSD clinically. 16 variations were detected in the 22 PTPSD cases. The 5 variations, p.Lys77Arg, p.Ile84Phe, c.315-2A>G, c.244-2A>T, c.187-1G>T, were identified as novel variations. Two fetuses carried the same mutation with the proband and therefore were thought to be PTPSD fetuses. Three fetuses carried only one mutant allele and thus were thought to be PTPSD carriers.

Characteristics of phenylalanine hydroxylase gene mutation in patients with phenylketonuria in Ningxia area / 中华围产医学杂志

Objective To characterize the mutation of phenylalanine hydroxylase (PAH) gene in patients with phenylketonuria(PKU) in Ningxia area,China.Methods Seventy-three children diagnosed with PKU at the Child and Maternal Healthcare Hospital of Ningxia Hui Autonomous Region between January 2010 and June 2013,and 100 non-PKU children randomly chosen from children with normal results in PKU screening were enrolled in the study.Venous blood was collected and the PAH gene sequence was determined by direct DNA sequencing after amplification with the polymerase chain reaction technique.The new gene mutations were defined based on the national and international literature search and databases.The source of the newly discovered mutations was also measured by examining and sequencing the blood samples of their parents.The Chi-square test was used for statistical analysis.Results Among 146 alleles of the 73 PKU children,the detection rate of mutation of PAH gene was 79.5％ (116/146),including 37 types of mutations occurring in 11 exons other than exon 2 and exon 13.The 37 different mutations included 22 missense mutations (59.5％,22/37),six nonsense mutations(16.2％,6/37),six splice site mutations(16.2％,6/37) and three deletion mutations(8.1％,3/37).p.R243Q(17.1％,25/146),EX6-96A ＞ G (6.8％,10/146),p.R241C(6.2％,9/146),p.R413P (5.5％,8/146),p.Rl11X(4.8％,7/146) and IVS4-1G ＞ A(4.8％,7/146) were found to have a higher mutation frequency.Meanwhile,p.R243Q was the most common mutation among Han and Hui ethnic groups with a frequency of 18.8％(12/64) and 15.9％ (13/82),respectively.In contrast,p.R241C showed a significant higher frequency in the Hui group [9.8％(8/82) vs 1.6％(1/64),x2=4.17,P=0.04].Four new mutations of PAH genes,including p.Q304K,p.H107R,p.F392I and p.N223I,were discovered after literature search and comparative studies.Conclusions PAH gene mutations in children with PKU in Ningxia area are unique and are characterized by the diversity and complexity of mutation occurrence in this ethnic region.

Avaliação neuropsicológica de crianças e adolescentes com hiperfenilalaninemias / Neuropsychological evaluation of children and adolescents with hyperphenylalaninaemia

A fenilcetonúria é um erro inato do metabolismo, com incidência entre 1:10000 e 1:15000 nascidos vivos. Trata-se de uma doença de herança autossômica recessiva, caracterizada pela deficiência da enzima hepática fenilalanina hidroxilase ou de seu co-fator tetraidrobiopterina, que, na rota metabólica normal, são responsáveis por converter a fenilalanina em tirosina. O acúmulo de fenilalanina é tóxico ao Sistema Nervoso Central. O défict nos níveis de tirosina leva ao desequilíbrio metabólico que pode causar hipotonia, irritabilidade, letargia, tonturas, microcefalia, características autistas, défict cognitivo e atraso de desenvolvimento. O tratamento é baseado na dieta restrita em fenilalanina. Quando a dieta é iniciada precocemente, o prognóstico cognitivo é bom e os pacientes apresentam QI dentro da média. Embora não haja rebaixamento de QI, alguns estudos mostram que os resultados de avaliação neuropsicológica dos pacientes são piores do que irmãos e pares sem a doença, especialmente com relação a funções executivas. O objetivo deste trabalho foi avaliar e comparar o desempenho de crianças e adolescentes com fenilcetonúria tratados em um Serviço de Referência no Brasil em provas neuropsicológicas de memória e funções executivas, e comparar com aquele apresentado por pares sem a doença. Participaram do estudo 12 crianças e adolescentes com fenilcetonúria leve, oito com hiperfenilalaninemia permanentemente e uma com fenilcetonúria clássica. A idade do grupo caso índice variou entre seis e 15 anos (m=9,52±2,82)...

Phenylketonuria is an autossomal recessive metabolic disease caused by a mutation in the gene for the hepatic enzyme phenylalanine hydroxylase which makes it nonfunctional. It is one of the most common inborn errors of metabolism, with an incidence of 1:10000 to 1:15000 live births. Accumulation of PHE is toxic to the central nervous system. Low levels of tyrosine add to the metabolic abnormality and patients may present hypotonia, irritability, lethargy, dizziness, microcephaly, autistic features, cognitive impairment and developmental delay. The standard treatment is based on a lifelong diet with low levels of phenylalanine. When PKU restricted diet is started early in life, the cognitive outcome is excellent, and patients have normal IQ. Although there is no cognitive impairment, some studies showed that their neuropsychological scores might be lower than the ones of their peers and siblings, especially regarding executive functions. The objective of this study was to evaluate the neuropsychological performance of children and adolescents with the different types of hyperphenylalaninemia treated at a tertiary center in Brazil and compare with a control group with similar age and socioeconomic level. 12 children and teenagers with mild PKU, eight with HPA and one with classic PKU were evaluated. Age ranged between six and 15 years (m=9,52±2,82). Control group were formed by 21 non-pku children and teenagers with ages between six and 14 years (m=9,19±2,84), recruited in a public school. Neuropsychological evaluation was performed using the Wechsler Inteligence Scale for Children-III (WISC-III, Stroop Test, Rey Auditive Verbal Learning Test (RAVLT), Rey Visual Design Learning Test (RVDLT),Trail Making Test (TMT), Verbal Fluency Test (categorie: animals and letters F,A,S) and Hanoi Tower. This study was approved by the Ethical Committee of our institution...

Phenylketonuria, congenital hypothyroidism and haemoglobinopathies: public health issues for a Brazilian newborn screening program / Fenilcetonúria, hipotireoidismo congênito e hemoglobinopatias: questões de saúde pública para um programa de triagem neonatal brasileiro

In this study, the frequency of detected congenital hypothyroidism, phenylketonuria and haemoglobinopathies in the State of Rio de Janeiro's (Brazil) Newborn Screening Program (NBSP) was analyzed between the years of 2005 and 2007. There were two Newborn Screening Reference Centers (named NSRC A and B) with programmatic differences. In 2007, overall detection coverage reached 80.7%. The increase in the incidence of congenital hypothyroidism (1:1,030 in 2007) was attributed to the reduction of neonatal TSH value limits over time. The incidence discrepancy of phenylketonuria between NSRC A (1:28,427) and B (1:16,522) might be partially explained by the small number of cases. The incidence of sickle cell disease and its traits were uniformly high (1:1,288 and 1:21, respectively). This was coherent with the ethnic composition of the population. The differences in laboratory methods and critical values, in addition to other programmatic issues, may explain the variances in the results and limited analysis of the role of biological and environmental determinants in the occurrence of these diseases.

Neste estudo, foi analisada a frequência de detecção do hipotireoidismo congênito, fenilcetonúria e hemoglobinopatias no Programa de Triagem Neonatal do Estado do Rio de Janeiro, Brasil, entre 2005 e 2007. Havia dois Serviços de Referência em Triagem Neonatal (designados SRTN A e B) com diferenças programáticas. Em 2007, a cobertura alcançou 80,7%. O aumento na incidência do hipotireoidismo congênito (1:1.030 em 2007) foi atribuído à redução no valor de corte do TSH ao longo do tempo. As incidências discrepantes da fenilcetonúria entre os modelos (SRTN A - 1:28.427; SR-TN B - 1:16.522) podem ser parcialmente explicadas pelo pequeno número de casos. A incidência da doença falciforme e do traço falcêmico foi uniformemente elevada (1:1.288 e 1:21, respectivamente), sendo coerente com a composição étnica da população. As diferenças nos métodos laboratoriais e valores críticos, além de outras questões programáticas, podem explicar a variabilidade nos resultados e limitar a análise do papel dos determinantes biológicos e ambientais sobre a ocorrência das doenças.

Triagem neonatal para fenilcetonúria, hipotireoidismo congênito e hemoglobinopatias no recôncavo baiano: avaliação da cobertura em Cruz das Almas e Valença, Bahia, Brasil / Neonatal screening for phenylketonuria, congenital hypothyroidism and hemoglobinopathies: evaluation of cooverage in Cruz das Almas and Valença-Bahia, Brazil / Tamizaje neonatal para fenilcetonuria, hipotiroidismo congénito y hemoglobinopatías en el recóncavo baiano: evaluación de la cobertura en Cruz das Almas y Valença, Bahia, Brasil

O Programa de Triagem Neonatal (PTN) realizado pelo SUS na Bahia abrange o diagnóstico da fenilcetonúria (PKU), hipotireoidismo congênito (HC) e hemoglobinopatias, patologias que devem ser tratadas precocemente. O objetivo deste artigo é avaliar a cobertura do PTN e a incidência das doenças triadas em Cruz das Almas e Valença, Bahia. Trata-se de estudo descritivo de incidência das doenças triadas pelo Serviço de Referencia em Triagem Neonatal (SRTN)-APAE Salvador, com dados obtidos nos registros das Secretarias Municipais de Saúde (SMS) de Cruz das Almas e Valença, do Serviço de Referência em Tiragem Neonatal (SRTN) e do DATASUS, entre 2001 e 2009. Os resultados indicam que a cobertura observada foi crescente, alcançando 87,6% e 88,8%, respectivamente, em Valença e Cruz das Almas, em 2009. Nestes municípios, encontrou-se incidência de dois casos/1000 nascidos vivos(NV) para hemoglobinas variantes; 0,5 casos/1000NV para HC e nenhum caso de PKU, respectivamente. Incongruências quanto ao número de nativivos e amostras triadas pelo PTN foram observadas. Concluiu-se que houve aumento da cobertura do PTN, com incidência relevante de hemoglobinopatias nos municípios estudados. O sucesso da cobertura doprograma depende da adesão dos municípios, sendo necessária a implantação de um serviço de gestão dessas informações nas SMSs para planejamento de políticas de saúde pública.

The Neonatal Screening Program (NSP) in Brazil carried out by The Unique Health System (SUS) identifies the following congenital disorders: phenylketonuria, congenital hypothyroidism and hemoglobinapathies which should be treated in advance. The objective of this study is to evaluate the coverage of the neonatal Screening Program and the incidence of the identified disease by The Newborn Screening Reference Service at APAE-Salvador.The data were collected from registrations in The Municipal Department of health of Cruz das Almas e Valença, Newborn Screening Reference Service and DATASUS from 2001 to 2009. The results show that there was an increase in the coverage in Cruz das Almas (88.8%) and Valença (87.6%) respectively. In these two municipalities in Bahia it was found out an incidence of emoglobinapathies (two cases per 1000 live-births), three cases per 1000 congenital hypothyroidism and none of phenylketonuria. There were prominent inconsistencies in the registry of newborns and their blood samples as identified by the NSP. It can be concluded that there was an increase in the coverage of the NSP with relevant incidence of hemoglobinapathies in the municipalities studied. The success of the neonatal screening program in Cruz das Almas and Valença depends on the adherence of the municipalities. Therefore, it is necessary to implement a management service of information at the municipal Departments of health for planning public health policies.

El Programa de Tamizaje Neonatal (PTN) realizado por el SUS, en laBahia, abarca el diagnóstico de la fenilcetonuria (PKU), hipotiroidismo congénito (HC) y hemoglobinopatías, patologías que deben tratarse precozmente. El objetivo de este estudio es evaluar la cobertura del PTN y la incidencia de las enfermedades triadas en Cruz das Almas y Valença, Bahia. Estudio retrospectivo sobre la incidencia de enfermedades triadas por el Servicio de Referencia en Tamizaje Neonatal (SRTN) ? APAE, Salvador, con datos obtenidos en los registros de las Secretarías Municipales de Salud (SMS) de Cruz das Almas y Valença, del Servicio de Referencia en Tamizaje Neonatal (SRTN) y del DATASUS, entre los años de 2001 y 2009. Los resultados indican que la cobertura observada fue creciente alcanzando, en Valença y Cruz das Almas, 87,6% y 88,8%, respectivamente, durante el año de 2009. En estos municipios, se encontró, respectivamente, la incidencia de dos casos/1000 nacidos vivos(NV) de hemoglobinas variantes; 0,5 casos/1000 NV de HC y ningún caso de PKU. Fueron observadas incoherencias con relación al número de nacidos vivos y las muestras triadas por el PTN. Se concluye que, en los municipios investigados, hubo un aumento en la cobertura del PTN, con relevante incidencia de hemoglobinopatías. El suceso de la cobertura del programa depende de la adhesión de los municipios, siendo necesaria la implantación de un servicio de gestión de esas informaciones en las SMSs, para la planificación de políticas de salud pública.

Acompanhamento do aleitamento materno no tratamento de crianças com fenilcetonúria / Breastfeeding follow-up in the treatment of children with phenylketonuria

A fenilcetonúria (PKU) ocorre na incapacidade para transformar fenilalanina em tirosina, trazendo efeitos tóxicos para o sistema nervoso central. Tradicionalmente, no tratamento da PKU, o aleitamento materno é substituído por fórmula láctea. Este estudo verificou os efeitos do aleitamento materno como fonte de fenilalanina no desenvolvimento de crianças com PKU. Participaram dez lactentes com PKU, que iniciaram o tratamento com a introdução de fórmula láctea antes dos 30 dias e que mantiveram o aleitamento materno por no mínimo 30 dias de vida após o início dos procedimentos. Os procedimentos basearam-se em estimar a ingestão de leite materno, com margem segura da concentração da fenilalanina, calculando o volume gástrico e oferecendo inicialmente fórmula láctea, seguida do aleitamento materno em demanda livre, em todas as mamadas. O tempo de amamentação variou de um mês e cinco dias a 14 meses. Os controles sanguíneos foram semanais. Se o nível sérico da fenilalanina estivesse >2 mg/dL e <6 mg/dL mantinha-se a prescrição; se estivesse <2 mg/dL, diminuía-se a fórmula láctea em 25%, aumentando indiretamente o aleitamento materno; se estivesse >6 mg/dL, aumentava-se a fórmula em 50%. Avaliou-se os níveis de fenilalanina, aplicou-se a Early Language Milestone Scale e Passos Básicos do Desenvolvimento. Foram considerados adequados aqueles lactentes que apresentaram índices normativos em todas as avaliações. Dos lactentes, 80% conseguiram manter limites seguros da fenilalanina e desenvolvimento nos índices normativos. Há viabilidade da continuidade do aleitamento materno no tratamento de crianças com PKU desde que os níveis de fenilalanina sejam rigorosamente controlados e que os efeitos do aleitamento materno para o desenvolvimento infantil sejam verificados.

Phenylketonuria (PKU) is the inability to convert phenylalanine into tyrosine, causing toxic effects to the central nervous system. Traditionally, in the treatment of PKU, breastfeeding is replaced by formula milk. This study verified the effects of breastfeeding as a source of phenylalanine on the development of children with PKU. Participants were ten infants with PKU who started treatment with the introduction of formula before 30 days of life, and maintained breastfeeding for at least 30 days after the start of procedures. The procedures were based on estimating breast milk intake, with a safe margin of phenylalanine concentration, calculating stomach volume, and initially offering formula, then breastfeeding on free demand, at every feeding. Breastfeeding duration ranged from one month and five days to 14 months. Blood controls were tested weekly. If the serum level of phenylalanine was >2 mg/dL and <6 mg/dL, the prescription was kept; if it was >2 mg/dL, the formula was decreased by 25%, indirectly increasing breastfeeding; if it was <6 mg/dL the formula was increased by 50%. The phenylalanine levels were assessed, and the Early Milestone Scale and the Basic Steps of Development were applied. Those who had normative index in all evaluations were considered adequate. Eighty percent of infants were able to keep safe concentrations of phenylalanine and development within normal indices. Continued breastfeeding is viable in the treatment of children with PKU, provided that phenylalanine levels are strictly controlled and the effects of breastfeeding on child development are monitored.

Crianças com fenilcetonúria: avaliação audiológica básica e supressão das otoemissões / Children with phenylketonuria: basic audiological evaluation and suppression of otoacoustic emissions

OBJETIVO: Avaliar a via auditiva de crianças com fenilcetonúria tratadas precocemente, por meio de audiometria, imitanciometria e supressão das emissões otoacústicas transientes. MÉTODOS:Estudo prospectivo transversal comparativo com amostra composta por 28 crianças, sendo 12 com fenilcetonúria e 16 sem a doença. Foi realizada a pesquisa dos limiares de audibilidade por via aérea e óssea, logoaudiometria, imitanciometria e supressão das emissões otoacústicas transientes. RESULTADOS: A audiometria e a logoaudiometria estiveram normais em todos os participantes. Foram encontrados piores resultados para o índice de reconhecimento de fala (IRF) no grupo com fenilcetonúria. A imitanciometria revelou curva normal para todas as crianças, mas a pesquisa dos reflexos estapedianos demonstrou que as crianças do grupo com fenilcetonúria apresentaram aumento nos seus limiares nas frequências de 2 e 4 kHz. A supressão das emissões otoacústicas transientes não revelou diferença na comparação entre os grupos. CONCLUSÃO: A avaliação audiológica básica não identifica alterações na audição das crianças com fenilcetonúria, mas há pior discriminação ao IRF e aumento nos limiares de reflexos estapedianos nessas crianças, podendo indicar distúrbios do processamento auditivo. O estudo da supressão das otoemissões demonstra integridade do sistema eferente olivococlear medial nas crianças com fenilcetonúria.

PURPOSE: To evaluate the auditory pathways of children with early-treated phenylketonuria through audiometry, immitance tests, and suppression of transient otoacoustic emissions. METHODS: Prospective cross-sectional study with sample composed by 28 children: 12 with phenylketonuria and 16 without the disease. Participants underwent auditory evaluations composed of air- and bone-conduction pure-tone audiometry, speech audiometry, immittance tests and suppression of transient otoacoustic emissions. RESULTS: All participants presented normal results in pure-tone and speech audiometry; however, speech discrimination scores were lower on the phenylketonuria group. Immitance tests revealed normal tympanograms for all children, but stapedial reflex thresholds demonstrated higher thresholds in 2 and 4 kHz for children with phenylketonuria. The suppresion of transient otoacoustic emissions did not show difference in the comparison between groups. CONCLUSION: The basic audiologic assessment do not identify hearing disorders in children with phenylketonuria; however, speech discrimination scores were lower and stapedial reflexes were higher in these children, which may indicate auditory processing disorders. The study of the suppression of transient otoacoustic emissions demonstrated integrity of the olivocochlear efferent system in children with phenylketonuria.

Análise de desempenho do Programa de Triagem Neonatal do Estado do Rio de Janeiro, Brasil, de 2005 a 2007 / Performance analysis of the Rio de Janeiro State Neonatal Screening Program, 2005-2007

As diretrizes enfatizam o momento adequado para a coleta do teste de triagem neonatal entre o 3º e o 7º dias de vida, em 100 por cento dos recém-natos. O tratamento do hipotireoidismo congênito e da fenilcetonúria iniciado até 2 semanas de vida é capaz de evitar as sequelas neurológicas dessas doenças. O programa de triagem neonatal do Estado do Rio de Janeiro foi credenciado para Fase II do Programa Nacional de Triagem Neonatal com dois modelos de programa - modelo A e modelo B. Foi realizada análise de desempenho do PTN de 2005 a 2007. Entre 2002 e 2007, a cobertura foi crescente e chegou a 80,4 por cento, com 33,8 por cento das coletas realizadas até 7 dias. Ambos os modelos tiveram desempenhos semelhantes e aquém das metas preconizadas, com 50 por cento dos casos confirmados obtendo diagnóstico com mais de 48 dias de vida. Os atrasos acumulados nas diversas etapas do processo podem anular os benefícios da detecção precoce, fundamento da triagem neonatal. Os efeitos deletérios de longo prazo transcendem a esfera individual acarretando impacto no sistema de saúde e grande ônus social.

Guidelines emphasize that the appropriate time frame for neonatal screening with the heel stick test is from the 3rd to 7th day of life, in 100 percent of newborns. Treatment for congenital hypothyroidism and phenylketonuria, when initiated in the first two weeks of life, is capable of preventing the neurological sequelae of these diseases. The Rio de Janeiro State Neonatal Screening Program was accredited for Phase 2 of the National Neonatal Screening Program, with two program models (A and B). A performance analysis was conducted for the Neonatal Screening Program, for the years 2005 to 2007. Coverage increased from 2002 to 2007, reaching 80.4 percent, with 33.8 percent of the blood samples drawn in the first 7 days of life. The two models showed similar performance, short of the targets, with 50 percent of the confirmed cases receiving their diagnosis at more than 48 days of life. The delays accumulated in the various stages of the process can impede the benefits of early detection, the cornerstone of neonatal screening. The deleterious long-term effects transcend the individual sphere, with an impact on the health system and a major social burden.