Subject(s)
Neonatal Screening/history , Neonatal Screening/methods , Neonatal Screening/organization & administration , Infant, Newborn, Diseases/diagnosis , Infant, Newborn, Diseases/prevention & control , Phenylketonurias/diagnosis , Argentina , Adrenal Hyperplasia, Congenital/diagnosis , Congenital Hypothyroidism/diagnosis , Cystic Fibrosis/diagnosis , Galactosemias/diagnosisABSTRACT
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.
Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Phenylalanine/blood , Phenylketonurias/diagnosis , Phenylketonurias/metabolism , Body Composition/physiology , Metabolism, Inborn Errors/diagnosis , Phenylketonurias/epidemiology , Socioeconomic Factors , Case-Control Studies , Anthropometry/methods , Demography , Nutritional Status , Retrospective Studies , Cohort Studies , Overweight/epidemiology , Metabolism, Inborn Errors/blood , Metabolism, Inborn Errors/epidemiologyABSTRACT
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
Abstract Objectives To show the general prevalence and to characterize tetrahydrobiopterin (BH4) deficiencies with hyperphenylalaninemia, identified by the Neonatal Screening Program of the State of Minas Gerais. Methods Descriptive study of patients with BH4 deficiency identified by the Neonatal Screening Program of the State of Minas Gerais. Results The prevalence found was 2.1 for 1,000,000 live births, with a frequency of 1.71% among hyperphenylalaninemias. There were four cases (40%) with 6-pyruvoyl-tetrahydropterin synthase deficiency, three with GTP cyclohydrolase I - autosomal recessive form deficiency, and three with dihydropteridine reductase deficiency (30% each). Six patients were diagnosed due to clinical suspicion and four cases due to systematic screening in neonatal screening. After the start of the treatment, patients identified by neonatal screening had rapid improvement and improved neuropsychomotor development compared to those diagnosed by the medical history. Conclusions The prevalence of BH4 deficiencies in Minas Gerais was slightly higher than that found in the literature, but the frequency among hyperphenylalaninemias was similar. Although rare, they are severe diseases and, if left untreated, lead to developmental delays, abnormal movements, seizures, and premature death. Early treatment onset (starting before 5 months of age) showed good results in preventing intellectual disability, justifying the screening of these deficiencies in newborns with hyperphenylalaninemia identified at the neonatal screening programs for phenylketonuria.
Resumo Objetivos Apresentar a prevalência geral e caracterizar as deficiências de tetrahidrobiopterina - BH4 - com hiperfenilalaninemia, identificadas pelo Programa de Triagem Neonatal do Estadode Minas Gerais. Métodos Estudo descritivo de pacientes com deficiência de BH4 do Programa de Triagem Neonatal do Estado de Minas Gerais. Resultados A prevalência encontrada foi de 2,1 para 1.000.000 recém-nascidos vivos e a frequência de 1,71%, dentre as hiperfenilalaninemias. Quatro casos (40%) com deficiência de 6-piruvoil-tetrahidropterina sintase, três com deficiência de GTP ciclohidrolase I e três com deficiência de dihidropteridina redutase (30% cada um). Seis pacientes foram diagnosticadospor suspeita clínica e quatro pela pesquisa sistemática na triagem neonatal. Após o início do tratamento, os pacientes identificados pela triagem neonatal tiveram melhora rápida e melhor desenvolvimento neuropsicomotor em comparação com aqueles diagnosticados pela história clínica. Conclusões A prevalência das deficiências de BH4 em Minas Gerais foi um pouco maior que a encontrada na literatura, mas a frequência, entre as hiperfenilalaninemias, foi semelhante. Embora raras, são graves e, se não tratadas, levam a atraso de desenvolvimento, movimentos anormais, convulsões e morte precoce. O tratamento precoce (início antes dos 5 meses) mostrou bons resultados na prevenção de deficiência intelectual, justificando a pesquisa dessas deficiências nos recém-nascidos com hiperfenilalaninemia pelos programas de triagem neonatalpara fenilcetonúria.
Subject(s)
Humans , Male , Female , Infant, Newborn , Phenylketonurias/diagnosis , Phosphorus-Oxygen Lyases/deficiency , Phenylketonurias/complications , Phenylketonurias/epidemiology , Brazil/epidemiology , Prevalence , Cross-Sectional Studies , Retrospective Studies , Neonatal ScreeningABSTRACT
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)
Subject(s)
Humans , Phenylketonurias/diagnosis , Phenylketonurias/diet therapy , Phenylketonurias/genetics , Phenylketonurias/therapy , Phenylketonurias/etiology , Neonatal Screening/methodsABSTRACT
Las hiperfenilalaninemias se definen por un nivel sanguíneo de fenilalanina sobre 2 mg/dl. La principal causa es una mutación en el gen que codifica la fenilalanina hidroxilasa que cataliza la reacción que transforma la fenilalanina en tirosina. Las hiperfenilalaninemias se clasifican en benignas o leves, y las fenilcetonurias en leves, moderadas y clásicas. Debido a que su detección más allá del periodo neonatal causa retardo mental severo, desde 1992 en Chile su detección, junto con la del hipotirodismo congénito, es parte del Programa Nacional de Pesquisa Neonatal. Este artículo pretende responder las preguntas más comunes que se puede hacer el pediatra cuando enfrenta a un paciente con hiperfenilalaninemias.
Hyperphenylalaninaemias are defined by a blood phenylalanine over 2 mg/dl. The main cause is due to a mutation in the gene that codes the phenylalanine hydroxylase that catalyses the reaction that converts phenylalanine into tyrosine. The hyperphenylalaninaemias are classified into benign or mild hyperphenylalaninaemias, or mild, moderate or classic phenylketonurias. Due to its delayed detection outside the neonatal period it causes severe mental retardation. Its detection along with congenital hypothyroidism has been part of the National Neonatal Screening Program since 1992 in Chile. This article aims to answer the most common questions asked by the paediatrician when faced with a patient with hyperphenylalaninaemias.
Subject(s)
Humans , Infant, Newborn , Phenylalanine/blood , Phenylketonurias/diagnosis , Neonatal Screening/methods , Pediatrics , Phenylalanine Hydroxylase/genetics , Phenylalanine Hydroxylase/metabolism , Phenylalanine/metabolism , Phenylketonurias/complications , Phenylketonurias/genetics , Tyrosine/metabolism , Chile , Delayed Diagnosis , MutationABSTRACT
El test del piecito es un estudio que debe hacerse a todo recién nacido y sirve para diagnosticar enfermedades que pueden producir retardo mental. La detección temprana de los bebés afectados es muy importante para el éxito en la prevención de la enfermedad. Debe hacerse a todo recién nacido de manera obligatoria hasta los 30 días después del alumbramiento. En Paraguay la frecuencia de del Hipotiroidismo congénito es de alrededor 1 por cada 3.000 nacidos. El objetivo del presente trabajo es analizar la trascendencia que tuvo la realización del Test del piecito en la Unidad de Salud de la Familia (USF) de Capitán Meza Km. 16 durante los meses de Enero a Junio del 2015. Se realizó un estudio descriptivo, analítico, trasversal, retrospectivo, con metodología cuali-cuantitativa. Se revisaron en total 22 historias clínicas de niños a los que se les realizó el tamizaje neonatal. Los meses de Abril y Mayo fueron los que más Test del Piecito realizaron durante el periodo de estudio con un 22,73 % cada uno. Durante el periodo de estudio, el 100 % de los niños examinados tuvieron resultados negativos al Test del piecito. El sexo de los recién nacidos y sus lugares de procedencia no determinan la realización o no de los exámenes. Si bien el hecho de vivir en zonas alejadas pudiera significar un contratiempo en la accesibilidad al sistema de salud. Desde la toma de la muestra hasta la entrega de los resultados transcurren aproximadamente dos meses. Si los padres no se acercan a retirar los resultados estos se les llevan a su casa durante las visitas domiciliarias que se realizan como parte del trabajo de la atención primaria que desarrolla la USF de Capitán Meza Km. 16
The "Test del piecito" is a test that should be done every newborn and used to diagnose diseases that can cause mental retardation. Early detection of affected babies is very important for success in preventing disease. Everything must be done compulsorily newborn up to 30 days after delivery. In Paraguay the frequency of congenital hypothyroidism is about 1 per 3,000 births. The aim of this paper is to analyze the importance that had the realization of "Test del piecito" in Unit Family Health (USF) Capitan Meza Km. 16 during the months of January to June 2015. A descriptive study was conducted, analytical, transversal, and retrospective, with qualitative and quantitative methodology. Medical records of 22 children who underwent neonatal screening were reviewed in total. The months of April and May were the most "Test del piecito" performed during the study period with 22.73% each. During the study period, 100% of the children surveyed had negative results to "Test del piecito". The sex of newborns and their places of origin do not determine how or whether the exams. While the fact of living in remote areas could mean a setback in accessibility to health care. From sampling to delivery of results takes approximately two months. If parents do not come close to removing these results are taken home during home visits carried out as part of the work of primary care developed by the USF Capitan Meza Km. 16
Subject(s)
Humans , Male , Female , Infant, Newborn , Neonatal Screening , Phenylketonurias/diagnosis , Socioeconomic Factors , Cross-Sectional Studies , Retrospective Studies , Sex Distribution , Congenital Hypothyroidism/diagnosis , Intellectual Disability/prevention & controlABSTRACT
Objectives: Phenylketonuria (PKU) was the first inherited metabolic disease known to cause mental retardation for which a newborn screening program (NBS) was developed. The objective of this study was to evaluate the effectiveness of PKU NBS and the management of cases in the northeastern Brazilian state of Sergipe (SE).Materials and methods: We reviewed the phenylalanine concentrations in filter-paper collected from the heel (PKUneo) of 43,449 newborns; blood concentrations obtained by venipuncture in the subjects with abnormal PKUneo; the children’s age at several phases of the program, the incidence of the disease from January 2007 to June 2008; and metabolic control of the patients.Results: The coverage of NBS/SE was 78.93%. The children’s age was 10 ± 7 days at PKUneo collection. Twelve children were recalled based on the PKUneo cutoff value at 28 ± 13 days. From these, the concentrations of phenylalanine collected by venipuncture were normal in five children. The incidence of hyperphenylalaninemia was 1/43,449, and of PKU was 1/8,690 (5 cases). One suspected subject died. Another death occurred in the cohort, in a confirmed PKU case. PKU treatment began within 51 ± 12 days of life. In the four patients under dietary phenylalanine restriction, metabolic control was often difficult.Conclusions: PKU NBS/SE has satisfactory coverage and adequate cutoff for recalling patients and diagnosis, but the onset of treatment is delayed, and follow-up metabolic control is frequently inadequate.
Objetivos: A fenilcetonúria (PKU) foi a primeira causa metabólica hereditária de retardamento mental para a qual foi desenvolvido um programa de triagem em recém-nascidos (NBS). O objetivo deste estudo foi avaliar a eficácia do NBS para a PKU e o manejo dos casos em Sergipe (SE), Brasil.Materiais e métodos: Revisamos as concentrações de fenilalanina no filtro de papel coletado do calcanhar (PKUneo) de 43.449 recém-nascidos, suas concentrações de sangue obtidas por punção venosa em indivíduos com PKUneo anormal, a idade das crianças em diversas fases do programa, a incidência da doença no período de janeiro de 2007 a junho de 2008 e o controle metabólico dos pacientes.Resultados: A cobertura da NBS/SE foi de 78,93%. A idade das crianças era de 10 ± 7 dias na coleta de PKUneo. Doze crianças foram reconvocadas com base no ponto de corte de PKUneo aos 28 ± 13 dias de idade. Destas, as concentrações de fenilalanina por venipunctura foram normais em cinco. A incidência da hiperfenilalaninemia foi 1/43.449 e de PKU foi 1/8.690 (5 casos), e um indivíduo suspeito foi a óbito. Outro óbito ocorreu na coorte em um caso de PKU confirmado. O tratamento para a PKU começou com 51 ± 12 dias. Nos quatro pacientes sob restrição de fenilalanina alimentar, o controle metabólico foi frequentemente difícil.Conclusões: PKU NBS/SE apresenta uma cobertura satisfatória e ponto de corte adequado para reconvocação e diagnóstico, mas o início do tratamento é atrasado e o controle no seguimento é frequentemente inadequado.
Subject(s)
Female , Humans , Infant , Infant, Newborn , Male , Neonatal Screening/standards , Program Evaluation , Phenylalanine/blood , Phenylketonurias/diagnosis , Biomarkers/blood , Blood Specimen Collection/methods , Brazil/epidemiology , Cross-Sectional Studies , Incidence , Linear Models , Phenylketonurias/epidemiology , Reference ValuesABSTRACT
BACKGROUND: Defects either in phenylalanine hydroxylase (PheOH) or in the production and recycling of its cofactor (tetrahydrobiopterin [BH4]) are the causes of primary hyperphenylalaninemia (HPA). The aim of our study was to investigate the current status of different variants of HPA Kurdish patients in Kermanshah province, Iran. MATERIALS AND METHODS: From 33 cases enrolled in our study, 32 were identified as HPA patients. Reassessing of pre‑treatment phenylalanine concentrations and the analysis of urinary pterins was done by high‑performance liquid chromatography method. RESULTS: A total of 30 patients showed PAH deficiency and two patients were diagnosed with BH4 deficiency (BH4/ HPA ratio = 6.25%). Both of these two BH4‑deficient patients were assigned to severe variant of dihydropteridine reductase (DHPR) deficiency. More than 75% of patients with PAH deficiency classified as classic phenylketonuria (PKU) according their levels of pre‑treatment phenylalanine concentrations. CONCLUSION: Based on the performed study, we think that the frequency of milder forms of PKU is higher than those was estimated before and/or our findings here. Furthermore, the frequency of DHPR deficiency seems to be relatively high in our province. Since the clinical symptoms of DHPR deficiency are confusingly similar to that of classic PKU and its prognosis are much worse than classical PKU and cannot be solely treated with the PKU regime, our pilot study support that it is crucial to set up screening for BH4 deficiency, along with PAH deficiency, among all HPA patients diagnosed with HPA.
Subject(s)
Adolescent , Child , Child, Preschool , Consanguinity , Female , Humans , Iran , Male , Phenylketonurias/diagnosis , Phenylketonurias/epidemiology , Phenylketonurias/genetics , Phenylalanine Hydroxylase/deficiency , Phenylalanine Hydroxylase/etiology , Phenylalanine Hydroxylase/genetics , Young AdultABSTRACT
OBJETIVO: Avaliar o Programa de Triagem Neonatal do Estado do Tocantins de 1995 a 2011. MATERIAIS E MÉTODOS: A coleta de dados foi realizada por meio de entrevista com os responsáveis pelo serviço, por análise de prontuários de pacientes com diagnóstico de fenilcetonúria (PKU) ou hipotireoidismo congênito (HC) atendidos pelo programa e por entrevista com pais e/ou responsáveis por pacientes em acompanhamento. RESULTADOS: A cobertura de triagem neonatal aumentou de 32,3% para 76,6% depois da implantação do Programa Nacional de Triagem Neonatal (PNTN). A prevalência de PKU e de HC no período analisado foi de 1:28.309 e de 1:4.632 nascidos vivos, respectivamente. A idade média das crianças na coleta da primeira amostra de sangue (PKU: 9,6 ± 6,3 dias; HC: 13,3 ± 10,3 dias) e no início do tratamento (PKU: 57,0 ± 17,6 dias; HC: 95,6 ± 57,6 dias) foi superior às preconizadas pelo Ministério da Saúde. A avaliação dos pais sobre a qualidade do acompanhamento realizado foi classificada como satisfatória por 100% dos entrevistados. CONCLUSÃO: Embora tenha havido grande evolução do programa de triagem neonatal deste Estado, há necessidade de maior incentivo governamental para que o programa seja otimizado e possa avançar para as fases seguintes do PNTN.
OBJECTIVE: To evaluate the Neonatal Screening Program in the State of Tocantins from 1995 to 2011. MATERIALS AND METHODS: Data collection was conducted by means of interviews with those responsible for the service, by the analysis of medical records of patients diagnosed with phenylketonuria (PKU) and congenital hypothyroidism (CH) that were enrolled in the program, and by interviews with parents and/or guardians of the patients monitored. RESULTS: Program coverage increased from 32.3% to 76.6% after the implementation of the National Newborn Screening Program (PNTN). The prevalence of PKU and CH was 1:28,309 and 1:4,632 live births, respectively. The mean ages at the collection of the first blood sample (PKU: 9.6 ± 6.3 days; CH: 13.3 ± 10.3 days) and at the beginning of the treatment (PKU: 57.0 ± 17.6 days; CH: 95,6 ± 57.6 days) were greater than recommended by the Ministry of Health. The quality of monitoring was considered satisfactory by 100% of the parents. CONCLUSION: Although there have been great developments in neonatal screening program in this state, there is need for greater government incentives to optimize the program and to make the PNTN advance to its next phases.
Subject(s)
Female , Humans , Infant, Newborn , Male , Congenital Hypothyroidism/diagnosis , Neonatal Screening/standards , Phenylketonurias/diagnosis , Brazil/epidemiology , Cross-Sectional Studies , Congenital Hypothyroidism/epidemiology , National Health Programs , Prevalence , Program Evaluation , Phenylketonurias/epidemiology , Quality Assurance, Health CareABSTRACT
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.
Subject(s)
Humans , Infant, Newborn , Congenital Hypothyroidism/epidemiology , Hemoglobinopathies/epidemiology , Neonatal Screening , Phenylketonurias/epidemiology , Brazil/epidemiology , Congenital Hypothyroidism/diagnosis , Hemoglobinopathies/diagnosis , Incidence , Phenylketonurias/diagnosis , Retrospective Studies , Rare Diseases/diagnosis , Rare Diseases/epidemiologyABSTRACT
Introdução: A Fenilcetonúria Clássica é causada pela deficiência da enzima hepática fenilalaninahidroxilase. Se não diagnosticada e tratada precocemente, causa retardo mental. O objetivo deste estudo foi identificar indivíduos submetidos à triagem neonatal no Rio Grande do Sul entre 1986 e 2003, com teste positivo para hiperfenilalaninemia, estimar a prevalência de hiperfenilalaninemias, verificar níveis de controle e correlacionar os anos de realização do teste, início do tratamento, evolução e quadro clínico. Métodos: Casos de hiperfenilalaninemia foram identificados nos laboratórios e clínicas de tratamento. Foi aplicado questionário, contendo variáveis demográficas e sobre a patologia, o desenvolvimento infantil, a escolaridade, o aconselhamento genético e o rastreamento neonatal. Foram avaliados pacientes entre 6 meses e 16 anos de idade. Na análise estatística, utilizou-se o teste do qui-quadrado e ANOVA para avaliar a associação entre ano do diagnóstico e controle de fenilalanina e regressão logística para avaliar o efeito conjunto de idade do diagnóstico e controle de fenilalanina sobre o atraso no desenvolvimento. Resultados: De 1986 a 2003, 418 crianças apresentaram teste positivo para fenilalanina. Destes, 351 (84,0%) apresentaram resultados normais na segunda amostra, 58 (13,9%) foram considerados portadores de hiperfenilalaninemia e 9 (2,1%) tiveram o seguimento perdido. A cobertura do programa foi de 50%. Sobre o aconselhamento genético, 39 entrevistados (72,2%) responderam não saber, não lembrar ou deram respostas incorretas. Conclusão: Não se observou tendência histórica do diagnóstico ter se tornado mais precoce ou do controle laboratorial ter se tornado melhor. O controle bioquímico da fenilalanina não dependeu da precocidade do diagnóstico e sim, da idade dos pacientes.
Introduction: Classical phenylketonuria is caused by deficiency of the hepatic enzyme phenylalanine hydroxylase. If not diagnosed and treated early, it causes mental retardation. The aim of this study was to identify patients who underwent neonatal screening in Rio Grande do Sul between 1986 and 2003 and tested positive for hyperphenylalaninemia, to estimate the prevalence of hyperphenyl-alaninaemias, to check the levels of control, and to correlate the years of testing, initiation of treatment, evolution and clinical picture. Methods: Cases of hyperphenylalaninemia were identified in laboratories and treatment clinics. A questionnaire was administered containing demographic variables and about the pathology, child development, education, genetic counseling and neonatal screening. We evaluated patients between 6 months and 16 years of age. The statistical analysis used the chi-square test and ANOVA to assess the association between year of diagnosis and control of phenylalanine and logistic regression to assess the combined effect of age at diagnosis and control of phenylalanine on the developmental delay. Results: From 1986 to 2003, 418 children tested positive for phenylalanine. Of these, 351 (84.0%) had normal results in the second sample, 58 (13.9%) were considered with hyperphenylalaninemia, and 9 (2.1%) were lost for follow-up . The coverage of the program was 50%. Concerning genetic counseling, 39 respondents (72.2%) reported not knowing, not remembering or gave incorrect answers. Conclusion: There was no historical trend of diagnosis having become earlier or of laboratory control having improved. The biochemical control of phenylalanine was dependent on patient age rather than on early diagnosis.
Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Phenylalanine Hydroxylase/deficiency , Phenylalanine Hydroxylase/metabolism , Fetal Mortality , Neonatal Screening , Cohort Studies , Risk Factors , Phenylketonurias/diagnosis , Phenylketonurias/epidemiologyABSTRACT
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.
Subject(s)
Humans , Infant, Newborn , Congenital Hypothyroidism/diagnosis , Neonatal Screening , Phenylketonurias/diagnosis , Brazil , National Health Programs , Program EvaluationABSTRACT
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
A fenilcetonúria é ocasionada por mutações no gene que codifica a enzima fenilalanina-hidroxilase, responsável pela transformação do aminoácido fenilalanina em tirosina. É detectada pelo teste do pezinho que permite seu diagnóstico e tratamento precoces. As crianças não tratadas apresentam comprometimento progressivo na função cerebral. A hiperfenilalaninemia transitória origina-se do atraso na maturação do sistema enzimático de hidroxilação. Os níveis séricos de fenilalanina estão maiores que o limite superior da normalidade, mas inferiores aos da fenilcetonúria clássica, decrescendo com o tempo, sem causar sintomas. O objetivo desse trabalho é relatar um caso de hiperfenilalaninemia transitória em uma criança nascida em Juiz de Fora - MG, atualmente em acompanhamento pelo Programa de Follow-up de Recém Nascidos de Alto Risco. Crianças com erros inatos do metabolismo são frequentemente acompanhadas em centros especializados, mas o pediatra geral deve estar atento a essas patologias, pois participará da verificação do uso adequado da dieta, quando necessária, e acompanhará o crescimento e desenvolvimento da criança.
Phenylketonuria is caused by mutations of the gene coding for phenylalanine hydroxylase, an enzyme responsible for the conversion of the amino acid phenylalanine into tyrosine. The condition is detected by neonatal screening, which allows for early diagnosis and treatment. Untreated children have progressive cerebral impairment. Transient hyperphenylalaninemia is due to a delayed maturation of the hydroxylation enzymatic system. Although serum phenylalanine levels are above the cut-off point, they are below those typically found in classic phenylketonuria, decreasing with time without generating symptoms. We report a case of transient hyperphenylalaninemia in a premature newborn from Juiz de Fora, MG, Brazil, who is being followed up by the special High Risk Neonate Program. Although children with inborn metabolic disorders are frequently followed up in specialized centers, general pediatricians must be aware of these diseases, as they will play an important role in diet, growth and development monitoring.
Subject(s)
Phenylalanine , Phenylketonurias , Phenylketonurias/diagnosis , Infant, Premature , Metabolism, Inborn ErrorsABSTRACT
O Programa de Triagem Neonatal do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Brasil, instituído em 1994 diagnosticou, até 2005, 76 crianças com hipotireoidismo congênito, 10 com fenilcetonúria e 25 com hemoglobinopatias, o que representou uma incidência de 1:2.595, 1:19.409, 1:4.120, respectivamente. Foram diagnosticadas 2.747 crianças com traço falciforme (1:37,5 nascidos vivos). A cobertura média do programa foi de 94,5 por cento. Houve uma considerável melhora nos parâmetros de avaliação da qualidade do programa no período, porém, sem atingir os índices ideais. Campanhas visando à maior divulgação da importância da triagem neonatal são necessárias para aumentar a cobertura e a instituição do 3º dia de vida do recém-nascido como sendo o Dia do Teste do Pezinho poderia contribuir para que idades mais precoces de tratamento fossem atingidas, melhorando o prognóstico das crianças acometidas.
The Neonatal Screening Program at the University Hospital of the Ribeirao Preto School of Medicine, São Paulo University, Brazil, was introduced in 1994. As of December 2005, congenital hypothyroidism had been diagnosed in 76 infants, phenylketonuria in 10, and hemoglobinopathies in 25, representing incidence rates of 1:2,595, 1:19,409, and 1:4,120, respectively. A total of 2,747 newborns had the sickle cell trait, i.e., were heterozygous for the sickle mutation (1:37.5 live births). The program's mean coverage during this period was 94.5 percent. There was major improvement in the parameters for evaluating the program's quality, although they were still far from ideal. Public-awareness campaigns on the importance of neonatal screening are needed to increase the program's coverage. Setting postnatal day 3 as the standard Day for the Heel Stick Test would help ensure treatment at earlier ages, thus improving prognosis for affected infants.
Subject(s)
Humans , Infant, Newborn , Congenital Hypothyroidism/diagnosis , Hemoglobinopathies/diagnosis , Hospitals, University/statistics & numerical data , Neonatal Screening/standards , Phenylketonurias/diagnosis , Brazil , Neonatal Screening/methods , Retrospective StudiesABSTRACT
Classic phenylketonuria [PKU] is a rare metabolic disorder that results from a deficiency of a liver enzyme known as phenylalanine hydroxylase [PAH]. In this study, we researched about PKU epidemiological factors and health quality of patients after the neonatal screening program. Neonatal screening for PKU was conducted by one neonatal screening center in Fars Province, in Shiraz Paramedical University. All Fars infants must refer only to this center, in which a heel prick blood sample of each infant was collected at 72 hours postnatal on to standard filter paper and asked questions from the children's parent's and the doctor examined the patients receiving phenylalanine- free milk through examining the children's development. PKU was screened by Fluorometric method. Totally of 70477 newborns screened for PKU, 15- cases of PKU detected with an incidence of 1:4698. In "Eghlid", that is a city in Fars Province. The prevalence of the disease is 1:382 of newly born babies. The frequency of familial marriage in these children's parents is 86.6%. Twenty nine percent of them were observed among those who had married their close relatives. Mean rate of normal development in PKU patients was 95%.Consanguineous marriage is a major cause in that pattern particular in Iranian. The treatment of PKU after newborn screening is used. With special diet in above of 90% newborn is satisfactory. Now screening should be executed for all of family that they have familial history of PKU in Iran
Subject(s)
Humans , Phenylketonurias/diagnosis , Neonatal Screening , Consanguinity , Intellectual DisabilityABSTRACT
This study of Iranian families assessed the usefulness of carrier detection of phenylketonuria by variable number tandem-repeat [VNTR] polymorphism analysis. We studied 171 people [45 unrelated PKU subjects, and their parents and unaffected siblings]. Of 342 chromosomes [131 non-PKU and 211 PKU], 5 VNTR alleles were identified. This VNTR system would yield a polymorphism information content of 66%, comparable to that in Europeans and higher than in Chinese. Carrier detection by segregation analysis of VNTR was informative in 89.5% of siblings. We conclude that this polymorphism is highly informative in carrier detection of PKU in the Iranian population