Evaluation of newborn screening in the state of Mato Grosso from 2005 to 2019 / Avaliação da triagem neonatal no Estado de Mato Grosso no período de 2005 a 2019

ABSTRACT Objective: To evaluate quality indicators of the Neonatal Screening Referral Service of the state of Mato Grosso (NSRS-MT) from 2005 to 2019. Methods: Cross-sectional, retrospective, exploratory, descriptive, and observational study from 2005 to 2019. The following parameters were analyzed: age of newborns at the first collection, time between sample collection and arrival at the laboratory, time between the arrival and release of results and time between requesting the second sample and arrival at the NSRS. The population coverage of the program and the incidence of each clinical situation screened were also analyzed. Results: NSRS-MT coverage was analyzed and recorded as 76%. The incidence was analyzed for congenital hypothyroidism (CH) 1:1867, phenylketonuria (PKU) 1:33,311, sickle cell disease (SCD) 1:2004, cystic fibrosis (CF) 1:12,663, congenital adrenal hyperplasia (CAH) 1:15,843, and biotinidase deficiency (DB) 1:25,349. The median age (days) at the first consultation was: 44 for HC, 22 for PKU, 60 for DF, 52 for FC, 79 for HAC and 79 for DB. The mean time between exam collection and delivery to the NSRS was 8.4 days; between the arrival and release of results, 9 days; and for the return of recalls, 59 days. Conclusions: Regarding the coverage of the target population and collection at the ideal age, the NSRS-MT presents values below the national average. However, regarding the mean age at the time of the first consultation, the state's performance is better than the national.

RESUMO Objetivo: Avaliar indicadores de qualidade do Serviço de Referência em Triagem Neonatal do Estado de Mato Grosso (SRTN/MT) no período de 2005 a 2019. Métodos: Estudo transversal, retrospectivo, exploratório, descritivo e observacional, que utilizou dados do formulário FormSUS nos anos de 2005 a 2019. Foram analisados os seguintes parâmetros: idade dos recém-nascidos na primeira coleta, tempo entre coleta da amostra e chegada ao laboratório, tempo entre a chegada e a liberação dos resultados e tempo entre a solicitação da segunda amostra até a chegada ao SRTN. Foram analisadas, também, a cobertura populacional do programa e a incidência de cada situação clínica triada. Resultados: Cobertura do SRTN-MT: 76%. Incidências: hipotireoidismo congênito (HC) 1:1.867, fenilcetonúria (PKU) 1:33.311, doença falciforme (DF) 1:2.004, fibrose cística (FC) 1:12.663, hiperplasia adrenal congênita (HAC) 1:15.843 e deficiência de biotinidase (DB) 1:25.349. A mediana da idade (dias) na primeira consulta foi: 44 para HC, 22 para PKU, 60 para DF, 52 para FC, 79 para HAC e 79 para DB. A média entre a coleta do exame e a entrega no SRTN foi de 8,4 dias; entre a chegada e liberação dos resultados, de 9 dias; e para o retorno de reconvocados, de 59 dias. Conclusões: Com relação à cobertura da população alvo e a coleta na idade ideal, o SRTN apresenta valores abaixo da média nacional. Contudo, quanto à idade média no momento da primeira consulta, o desempenho de MT é melhor que a média nacional.

Hipoglicemia hipocetósica por deficiencia de carnitina en un niño

Durante el ayuno, la oxidación de ácidos grasos y la formación de cuerpos cetónicos son necesarios para la producción de energía. La carnitina es esencial para que los ácidos grasos de cadena larga se transfieran a la mitocondria para la oxidación de ácidos grasos. La deficiencia primaria de carnitina es un defecto recesivo que se expresa con un espectro clínico amplio que incluye descompensación metabólica, hipoglicemia hipocetósica o cardiomiopatía en la niñez, fatigabilidad en la adultez o ausencia de síntomas. En nuestro país no hay publicaciones sobre el tema, por lo que en el presente artículo se reporta el caso de un niño que presentó una deficiencia de carnitina expresada como hipoglicemia hipocetósica y se analiza sus hallazgos clínicos, bioquímicos e histopatológicos.

During fasting, the oxidation of fatty acids and the formation of ketone bodies are necessary for energy production. Carnitine is essential for long-chain fatty acids to be transferred to the mitochondria for fatty acid oxidation. Primary carnitine deficiency is a recessive defect that is expressed with a broad clinical spectrum that includes metabolic decompensation, hypoketotic hypoglycemia or cardiomyopathy in childhood, fatiguability in adulthood or absence of symptoms. In our country there are no publications on the subject, so this article reports the case of a child who had carnitine deficiency expressed as hypoketotic hypoglycemia and its clinical, biochemical and histopathological findings are analyzed.

Lethal mitochondrial trifunctional protein deficiency caused by HADHB gene variation: a case report / 中华围产医学杂志

This article reported a male neonate with lethal mitochondrial trifunctional protein deficiency (MTPD) caused by compound heterozygous variations in the HADHB gene. The patient presented with poor milk intake complicated by abnormal myocardial enzymes within 24 h after birth and was transferred to the Children's Hospital of Nanjing Medical University on day 4. Physical examination revealed no obvious abnormalities on admission. Laboratory examination showed increased creatine kinase isoenzyme and cardiac troponin levels, and electrocardiogram suggested sinus tachycardia and low QRS voltage in limb leads. Blood screening for metabolic abnormalities showed high levels of tetradecenyl carnitine and various 3-hydroxycarnitines. Heterozygous mutations of c.739C>T(p.Arg247Cys) and c.607C>T(p.Arg203Ter,272) were detected in the HADHB gene in the boy, which were pathogenic variants included in the Human Gene Mutation Database. Followed up to three months of age, the boy was readmitted to hospital due to poor milk intake for one week and poor response for 2 d after catching a cold. After admission, he quickly developed multiple organs dysfunction such as heart failure and respiratory failure, and then died. Lethal MTPD is rare with no effective treatment and poor prognosis. Lethal MTPD should be highly suspected when unexplained cardiomyopathy, hypoglycemia, acidosis and other metabolic abnormalities appear in the neonatal period, and an early diagnosis could be confirmed with genetic testing in the neonatal period.

Application of proteomics technology in diagnosis and pathogenesis of genetic metabolic diseases / 中华检验医学杂志

Inborn Errors of Metabolism (IEM) are diseases caused by genetic defects in the biosynthesis of certain enzymes, receptors, carriers and membrane pumps composed of peptides and/or proteins necessary to maintain normal metabolism of the body, namely, mutations in the genes encoding such peptides (proteins). Through metabolomic analysis of sugars, amino acids, organic acids, fatty acids, carnitine and other substances in blood or urine, as well as cellular enzymology, molecular biology and proteomics analysis. We can identify and quantify abnormal biomarks, determine biomarkers as diagnostic and therapeutic monitoring tools. At the same time, through proteomic research. We can provide scientific basis for the pathogenesis of hereditary metabolic diseases.

Usher syndrome with methylmalonic acidemia and homocysteine in an infant / 中华围产医学杂志

A case of Usher syndrome with methylmalonic acidemia and homocysteine is reported. The patient was a two-month-old and small for gestational age male infant hospitalized for "feeding difficulties" during the neonatal period. The baby boy presented hypotonia, microcephaly, and hearing loss after birth. Genetic test found compound heterozygous mutations of c.482G>A and c.567dup in MMACHC, and both were pathogenic mutations inherited from his parents. Moreover, the patient also had compound heterozygous variants at c.2802T>G and c.14017T>C of USH2A gene. The former was suspected to be pathogenic, and the latter was of unknown clinical significance. Both were from the parents. Usher syndrome and methylmalonic acidemia with homocysteine were clinically diagnosed. Followed up to the age of two, the child was found with moderate mental retardation, while the physical development was comparable to that of the same age group.

Neoseq for neonatal screening of fatty acid oxidation disorders / 中华围产医学杂志

Objective:To explore the value of Neoseq in screening and diagnosis of neonatal fatty acid oxidation disorders (FAOD).Methods:A retrospective case-control study was conducted on 163 500 live births in Changzhou city from April 2015 to April 2021. The following two models were adopted for FAOD screening and diagnosis. (1) Traditional mode: Heel blood samples were obtained from all subjects for initial screening using tandem mass spectrum (TMS), followed by next-generation sequencing (NGS) and other differential diagnostic testings for those with positive results. (2) Neoseq: Neoseq was performed on the true positive, negative and false positive cases according to the traditional mode screening results. The detection rate, additional discovery, reporting period, and other parameters of the two models for FAOD were described and compared.Results:(1) Detection and diagnosis of FAOD: A total of 18 confirmed cases of FAOD were detected through the traditional model, with an incidence of 1/9 083 in Changzhou city. The positive rate was 0.55% (907/163 500) for initial TMS and 0.04% (73/163 500) for the second. The positive predictive value was 2.0%(18/907), with a false positive rate of 98%(889/907) in the initial screening. (2) The results of Neoseq: ①Pathogenic mutations were detected in 16 of the 18 confirmed cases, and the coincidence rate of mutation sites between the two methods was 16/18. The other two confirmed cases were missed diagnosed by Neoseq, including one β-ketothiolase deficiency with only one detected pathogenic mutation and one medium-chain acyl-CoA dehydrogenase deficiency without any detected pathogenic mutation. ②No pathogenic mutations were detected in the 57 false-positive cases by Neoseq. ③Among the 100 negative cases in initial screening, DUOX2 heterozygous mutation, and MTTL1 hemizygous mutation were detected in one case each. ④The median period of results reporting was 43.5 d (28-104 d) for the traditional mode and 12 d (10-15 d) for the Neoseq mode. Conclusions:Neoseq has a high detection rate for FAOD. Combined with TMS screening, Neoseq reduces the false-positive rate of biochemical screening, rapidly identifies genetic causes by shortening the results waiting time and covers diseases that couldn't be detected by traditional biochemical methods.

Phenotype and genotype analysis of 6 patients with 21-hydroxylase deficiency / 中华全科医师杂志

The clinical data of 6 patients with 21-hydroxylase deficiency(21-OHD) diagnosed in The People′s Hospital of Xinjiang Uygur Autonomous Region from 2015 to 2020 were retrospectively analyzed. There were 2 male cases manifesting shorter height, high progesterone level and infertility. And 4 cases were females, manifesting primary amenorrhea, heterosexual precocious puberty, fatigue during emergency, decreased physical strength, dark skin, clitoral hypertrophy and vulva fusion. None of the parents had a history of consanguinity. All but one patient received glucocorticoid replacement therapy. The sequencing of exons and introns of 21CYPA2 gene showed tuat 1 case was homozygous mutation and 5 cases were complex heterozygous mutation. In terms of clinical phenotype, 1 case was non-classical (complex heterozygous mutation) and 5 cases were simple virilizing phenotype.

Desensibilización con idursulfase en un niño con síndrome de Hunter (mucopolisacaridosis II) / Idursulfase desensitization in a child with Hunter syndrome (mucopolysaccharidosis ii)

La terapia de reemplazo enzimático disminuye la morbilidad y mejora la calidad de vida de los pacientes con mucopolisacaridosisii. Se han descrito reacciones de hipersensibilidad inmediata a este fármaco. La desensibilización es un tratamiento que induce la tolerancia temporaria a una droga y permite al paciente alérgico recibir la medicación.Se presenta el caso de un niño de 7 años con diagnóstico de síndrome de Hunter que, luego de 4 años de tratamiento con idursulfase, tuvo dos episodios de anafilaxia durante la infusión del fármaco. Se detectó inmunoglubulina E específica mediante pruebas cutáneas, y fue positiva la intradermorreacción con dilución 1/10 (0,2 mg/ml). Se realizó un protocolo de desensibilización de 12 pasos, sin presentar eventos adversos. La evaluación alergológica y la posibilidad de desensibilización constituyeron herramientas útiles en el manejo de nuestro paciente

Enzyme replacement therapy with idursulfase decreases morbidity and improves quality of life of patients with mucopolysaccharidosis ii. Immediate hypersensitivity reactions to this drug have been described. Desensitization is a treatment that induces temporary tolerance to a culprit drug, allowing the allergic patient to receive the medication.We present the case of a 7-year-old patient diagnosed with Hunter syndrome who presented, after 4 years of treatment, two episodes of anaphylaxis during the infusion of idursulfase. Detection of specific immunoglobulin E was carried out using skin tests, with intradermal reaction at a 1/10 dilution (0.2 mg/ml) being positive. A 12-step desensitization protocol was performed without presenting adverse events.The allergological evaluation and the possibility of desensitization were useful tools in the management of our patient.

Mucopolysacaridosis type iiib misdiagnosed as an autistic spectrum disorder: a case report and literature review / Mucopolissacaridose tipo iii b mal diagnosticada como transtorno de espectro autista: relato de caso e revisão de literatura

ABSTRACT Objective: To report a rare case of mucopolysaccharidosis IIIB in a pediatric patient, with emphasis on the description of the clinical manifestations and the early diagnosis. Case description: A 14-year-old male patient, who presented regression of neuropsychomotor development since his three years and six months old, with speech loss and frequent falls, evolving with behavioral changes, with agitation and aggressiveness. Although being diagnosed with autism, there was no response to the established treatment; he was subsequently submitted to metabolic investigation, which lead to the diagnosis of Mucopolysaccharidosis IIIB. Comments: Identifying a metabolic disorder requires connecting multiple signs and symptoms, as well as eliminating other apparent causes. MPS IIIB is a diagnostic challenge, particularly in the early stages and in the absence of a family history of the disease.

RESUMO Objetivo: Relatar o caso raro de um paciente pediátrico com mucopolissacaridose III B, com ênfase na descrição de manifestações clínicas. Descrição do caso: Paciente masculino de 14 anos que, a partir dos 3 anos e 6 meses de idade, apresentou regressão do desenvolvimento neuropsicomotor, com perda da fala e quedas frequentes, evoluindo com alterações comportamentais, agitação e agressividade. Diagnosticado como autista, não obteve resposta ao tratamento estabelecido, sendo posteriormente submetido à investigação metabólica, que evidenciou o diagnóstico de mucopolissacaridose III B. Comentários: A identificação de um distúrbio metabólico exige conectar vários sinais e sintomas, além de eliminar outras causas aparentes. A mucopolissacaridose III B é um desafio diagnóstico, particularmente nos estágios iniciais e na ausência de história familiar da doença.

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.

Equipe de enfermagem no cuidado à criança com doença de Pompe em terapia intensiva / Nursing team in care for children with Pompe disease in intensive care / Equipo de enfermería en la atención de niños con enfermedad de Pompe en cuidados intensivos

Objetivo: investigar o conhecimento e práticas da equipe de enfermagem em relação ao cuidado à criança com Doença de Pompe em terapia intensiva. Método: trata-se de um estudo descritivo com abordagem qualitativa. A coleta de dados foi realizada com entrevista semiestruturada com enfermeiras e técnicas em enfermagem que atuavam na Unidade de Terapia Intensiva Neonatal de um hospital do Rio Grande do Sul, após aprovação pelo Comitê de Ética em Pesquisa. Os dados foram analisados pela análise de conteúdo. Resultados: as profissionais enfatizaram experiências que superam procedimentos técnicos, na busca de fornecer um cuidado integral qualificado e seguro, para proporcionar vivências mais próximas de um lar para a criança e familiares. Conclusão: a equipe de enfermagem possui conhecimentos para o cuidado e atua de forma multiprofissional. Conclui-se que estudos relacionados às doenças raras oferecem subsídios para qualificar o cuidado de enfermagem.

Objective: to investigate nursing team knowledge and practices regarding care for children with Pompe disease in intensive care. Method: in this qualitative, descriptive study, data were collected by semi-structured interviews of nurses and nursing technicians working in the neonatal intensive care unit of a hospital in Rio Grande do Sul, after ethics committee approval. Data were subjected to content analysis. Result: the nurses emphasized experiences that go beyond technical procedures, in the endeavor to provide safe and qualified comprehensive care in order to provide experiences closer to a home for the children and their families. Conclusion: the nursing team was knowledgeable about care and worked in multidisciplinary manner. It was concluded that studies relating to rare disease offer input to inform nursing care.

Objetivo: investigar el conocimiento y las prácticas del equipo de enfermería sobre el cuidado de niños con enfermedad de Pompe en cuidados intensivos. Método: en este estudio cualitativo descriptivo, los datos fueron recolectados mediante entrevistas semiestructuradas a enfermeras y técnicos de enfermería que laboran en la unidad de cuidados intensivos neonatales de un hospital de Rio Grande do Sul, previa aprobación del comité de ética. Los datos se sometieron a análisis de contenido. Resultado: las enfermeras destacaron experiencias que van más allá de los procedimientos técnicos, en el afán de brindar una atención integral segura y calificada con el fin de brindar experiencias más cercanas a un hogar para los niños y sus familias. Conclusión: el equipo de enfermería tenía conocimiento del cuidado y trabajaba de manera multidisciplinar. Se concluyó que los estudios relacionados con las enfermedades raras ofrecen información para informar la atención de enfermería.

Características electroclínicas en pacientes menores de 18 años con errores innatos del metabolismo (EIM) y epilepsia

INTRODUCCIÓN: Los errores innatos del metabolismo (EIM) son un grupo de enfermedades de origen genético, que entre el 40 % y el 60 % pueden manifestar crisis convulsivas. OBJETIVO: En este estudio se establecieron las características clínicas y electroencefalográficas en una muestra de 20 niños con diagnóstico de EIM y epilepsia. MATERIALES Y METODOS: La metodología utilizada fue un estudio descriptivo de series de casos retrospectivo. RESULTADOS: El 65 % de los pacientes de la muestra eran niños, el EIM de moléculas pequeñas fue el más frecuente (70 %). En cuanto a las variables clínicas, 90 % tenían encefalopatía, 75 % epilepsia refractaria y 55 °% crisis generalizadas. En electroencefalografía (EEG), 90 % de los pacientes tenían ritmo de fondo anormal, 80 % grafoelementos del sueño mal estructurados, 36 % de los afectados por EIM de moléculas pequeñas tenían patrón EEG multifocal y 100 % de los pacientes con déficit de producción de energía tuvieron patrón EEG focal. CONCLUSION: El tipo de EIM más frecuente en el estudio fue de moléculas pequeñas, con grados variables de encefalopatía y epilepsia refractaria. La anormalidad electroencefalográfica más frecuente fue el ritmo de fondo anormal debido a grafoelementos de sueño mal estructurados, en tanto que el patrón eléctrico fue dependiente de la edad y el tipo de EIM.

SUMMARY INTRODUCTION: Inborn errors of metabolism (IEM) are a group of diseases of genetic origin and they may manifest with seizures at some point of their evolution such as 40 to 60 percent of cases. SUBJECT: In this study, the clinical and electroencephalographic characteristics were established in a sample of 20 children diagnosed with IEM and epilepsy. METHODS: The methodology was a descriptive way of retrospective case series. RESULTS: The group was constituted 65 % by males. The EIM of small molecules was the most frequent (70 %). Regarding the clinical variables, 90 % had encephalopathy, 75 % refractory epilepsy and 55 % generalized epilepsy. About the electroencephalographic facts, 90 % had an abnormal basal activity, 80 % poorly structured sleep elements. The most frequent electroencephalographic pattern in small molecules disease's patients was multifocal (36 %) but in deficit of energy production's patients was focal (100 %). CONCLUSION: The type of IEM that predominated in this study was small molecules, with varying degrees of encephalopathy and refractory epilepsy. The most frequent electroencephalographic variable was abnormal background rhythm, with poorly structured sleep graphoelements. The electroencephalographic pattern depends on the age and type of IEM.

Case series of patients under biweekly treatment with laronidase: a report of a single center experience / Série de casos de pacientes em tratamento com laronidase quinzenal: relato da experiência de um centro

ABSTRACT Objective: To report the stabilization of urinary glycosaminoglicans (GAG) excretion and clinical improvements in patients with mucopolysaccharidosis type I (MPS I) under an alternative dose regimen of laronidase of 1.2 mg/kg every other week. Methods: We participated in a dose-optimization trial for laronidase in MPS-I patients using four alternative regimens: 0.58 mg/kg every week, 1.2 mg/kg every two weeks, 1.2 mg/kg every week and 1.8 mg/kg every other week (EOW). After the trial ended, the patients resumed the recommended dose and regimen of 0.58 mg/kg every week. Under this regimen, some patients presented difficulties in venous access and were unable to commute weekly to the treatment center. Therefore, we used an alternative regimen that consisted of 1.2 mg/kg EOW in eight patients. A retrospective study of medical records of MPS-I patients who underwent both enzyme replacement therapy (ERT) regimens, of 0.58 mg/kg every week and 1.2 mg/kg EOW, was done. Results: Patients remained clinically stable under the alternative regimen, did not present elevation of urinary GAG nor any adverse event. Conclusions: The switch of dose regimen to 1.2 mg/kg EOW of laronidase was safe, and did not cause any clinical worsening in patients who had been previously under standard dose ERT.

RESUMO Objetivo: Descrever a manutenção dos níveis de glicosaminoglicano (GAG) excretados na urina e da estabilização clínica em pacientes com mucopolissacaridose do tipo I (MPS I) com o uso da laronidase num regime de dose alternativo de 1,2 mg/kg a cada duas semanas. Método: Alguns pacientes do nosso serviço participaram de um estudo de otimização de dose da laronidase para o tratamento da MPS I no qual foram comparados quatro esquemas terapêuticos: 0,58 mg/kg/semana, 1,2 mg/kg a cada duas semanas, 1,2 mg/kg/semana e 1,8 mg/kg a cada duas semanas. Após o término do estudo, todos os pacientes passaram a receber a terapia de reposição enzimática (TRE) na dose padrão de bula, que é de 0,58 mg/kg/semana, e nesse regime alguns pais se queixaram da dificuldade em comparecer ao centro todas as semanas, além da dificuldade de se obter acesso para punção venosa. Com base nessas queixas, oito pacientes passaram a receber a TRE no regime alternativo de 1,2 mg/kg a cada duas semanas. Foi feito o estudo retrospectivo de dados de prontuário de pacientes com MPS I que fizeram TRE com laronidase nas doses 0,58 mg/kg/semana e 1,2 mg/kg a cada duas semanas. Resultados: Os pacientes mantiveram-se clinicamente estáveis, não apresentaram aumento dos níveis de GAG urinários nem eventos adversos durante o regime alternativo de dose. Conclusões: A mudança para o esquema de 1,2 mg/kg de laronidase a cada duas semanas foi segura e não acarretou piora clínica nos pacientes que já estavam em TRE na dose padrão.

Teste do pezinho: condições materno-fetais que podem interferir no exame em recém-nascidos atendidos na unidade de terapia intensiva / Heel prick test: maternal-fetal conditions that may have an effect on the test results in newborns admitted to the intensive care unit

RESUMO Objetivo: Descrever as características do teste do pezinho dos neonatos atendidos na unidade de terapia intensiva de um hospital universitário, bem como verificar se existiam condições maternas e fetais que pudessem interferir no resultado desse exame. Métodos: Estudo retrospectivo longitudinal de abordagem quantitativa que avaliou 240 prontuários médicos. Os dados coletados foram submetidos à análise estatística descritiva. Resultados: Houve predomínio de gestantes com idades entre 20 a 34 anos, com Ensino Médio completo e que realizaram mais de seis consultas pré-natais. As intercorrências ou patologias maternas ocorreram em 60% das mães, e a maioria (67,5%) não apresentou nenhuma condição que pudesse interferir no resultado do teste do pezinho. A maioria dos neonatos era prematura e exibiu baixo peso ao nascimento. Cerca de 90% dos neonatos exibiram condições que poderiam influenciar no exame, principalmente prematuridade, nutrição parenteral e transfusão sanguínea. Dos 240 neonatos, 25% apresentaram resultado alterado no teste do pezinho, sobretudo para fibrose cística e hiperplasia adrenal congênita. Conclusão: Existem condições maternas e neonatais que podem interferir no teste do pezinho e, nesse sentido, sua investigação é imprescindível, visando direcionar ações que promovam a saúde materno-infantil e consolidem a triagem neonatal nessa população.

ABSTRACT Objective: To describe the characteristics of the heel prick test in newborns admitted to the intensive care unit of a university hospital as well as to determine whether maternal and fetal conditions could have affected the results of this test. Methods: Retrospective longitudinal study with a quantitative approach that evaluated 240 medical records. The data collected were analyzed by descriptive statistical analysis. Results: There was a predominance of pregnant women aged 20 to 34 years who had a complete secondary education and who had more than six prenatal care visits. Maternal complications or pathologies occurred in 60% of the mothers, and most (67.5%) did not present any condition that could have affected the heel prick test results. Most newborns were premature and exhibited low birth weight. Approximately 90% of newborns exhibited conditions that could have influenced the test, especially prematurity, parenteral nutrition and blood transfusion. Of the 240 newborns, 25% had abnormal heel prick test results, especially for cystic fibrosis and congenital adrenal hyperplasia. Conclusion: There are maternal and neonatal conditions that can affect heel prick test results, and therefore, their investigation is essential, aiming to guide measures that promote mother and child health and consolidate neonatal screening in this population.

Pathogenic mechanism and clinical diagnosis of hereditary abnormal copper metabolism / 临床肝胆病杂志

Copper is an important trace element in the human body, and copper deficiency or overload can lead to a series of body dysfunctions. This review focuses on hepatolenticular degeneration and related diseases of abnormal copper metabolism. Hepatolenticular degeneration has various clinical phenotypes, and related diseases, such as cholestatic liver disease, hereditary ceruloplasmin deficiency, and congenital abnormal glycosylation, may bring confusion to the clinical diagnosis of hepatolenticular degeneration. With reference to the latest research advances and experience in the diagnosis and treatment of hepatolenticular degeneration, this article discusses the pathogenic mechanism and clinical diagnosis of hereditary abnormal copper metabolism from the perspective of liver diseases.

Three cases of carnitine-acylcarnitine transposase deficiency and literature review / 中国新生儿科杂志

Objective To study the clinical features,biochemical characteristics and gene mutations of patients with carnitine-acylcarnitine translocase deficiency (CACTD).Method The clinical data,biochemical markers and gene mutations of three cases with CACTD admitted our hospital in 2017 were retrospectively analyzed.The related literatures were searched from China national knowledge infrastructure,wanfang database,PubMed,national center for biotechnology information and Embase using keywords "neonate","infant","carnitine-acylcarnitine deficiency","carnitine-acylcarnitine translocase",and SLC25A20"(up to April 2018).Result (1) Three cases (2 boys and 1 girl) with CACTD were full-term infants without asphyxia after birth.The mothers had no abnormal pregnancy,and the parents had no consanguinity.All the patients had poor response and severely hypoglycemia 15～20 hours after birth.Hyperammonemia,elevated liver enzymes and creatine kinase,severe dicarboxylic aciduria,significantly increased level of long-chain acylcarnitine,and significantly decreased concentration of free carnitine were observed in all 3 patients.Significantly decreased serum ketone body was observed in 2 cases.All of them had recurrent atrioventricular block and ventricular tachycardia requiring repeated electrocardioversion,lidocaine,and amiodarone treatment.Arginine,carnitine and special formula with low fat and high medium-chain-triglyceride were given to two infants.Two infants died of cardiorespiratory failure at 3-day and 8-day of life,respectively.The other infant's clinical condition improved significantly.However,he was discharged from our NICU at the request of his parents.Gene analysis revealed that compound heterozygous mutations c.199-10T＞G and IVS7-9_16 ins (a possible novel mutation) were detected in the SLC25A20 gene of case 2.Homozygous mutation c.199-10T＞G was identified in the SLC25A20 gene of case 3 whose parents both carried this mutation.(2) A total of 17 articles and 50 cases were retrieved and analyzed.A total of 40 mutations were found in the SLC25A20 gene.Homozygous mutations were found in 23 cases,and compound heterozygous mutations were found in 27 cases.The mutation of c.199-10T＞G was the most common mutation and occurred 22 times in the patients from Asia population.Other mutations were found less than 6 times.The review showed that the most common clinical features included hypoketotic hypoglycemia,hyperammonemia,elevated liver enzymes and creatine kinase,remarkable dicarboxylic aciduria,significantly increased level of long-chain acylcarnitine,significantly decreased free carnitine,arrhythmia and cardiomyopathy.Mostly,the onset of symptoms was within 1 week after birth (88％,44/50).The mortality was 69.8％ (30/43).Most patients died within the first year of their life.Conclusion Early recognition,early diagnosis and prompt treatment are crucial for CACTD patients.Gene analysis is a reliable diagnostic method.The mutation of c.199-10T＞G is the most common SLC25A20 mutation reported in Asia population.Hypoketotic hypoglycemia is an early sign of this disease.Families with a proband need prenatal diagnosis during the second pregnancy.

Carnitine-acylcarnitine translocase deficiency with homozygous mutation of c.199-10T＞G: a case report and literature review / 中华围产医学杂志

Objective To investigate the clinical features of carnitine-acylcarnitine translocase deficiency (CACTD) with c.199-10T＞G homozygous mutation and the characteristics of SLC25A20 gene mutation.Methods This study retrospectively analyzed the clinical data,biochemical and genetic features,treatment and outcome of a boy with CACTD with c.199-10T＞G homozygous mutation,who admitted to Guangzhou Women and Children's Medical Center in September 2017.Pertinent articles were retrieved from China National Knowledge Infrastructure (CNKI),Wanfang Database,National Center for Biotechnology Information and PubMed from the establishment of these databases to April 2018 using key words including CACT,SLC25A20 and carnitine-acylcarnitine translocase.Clinical information of all affected cases in the retrieved publications was analyzed.Results (1) The full-term boy born vaginally at a local hospital was transferred to neonatal intensive care unit (NICU) of Guangzhou Women and Children's Medical Center at 2 days and 5 hours due to groaning,cyanosis and severe hypoglycemia (0.8 mmol/L) at 15 h after birth.His elder brother with similar symptoms died of unknown reason at 50 days of age.In this case,ammonemia,liver enzyme and creatine kinase were significantly elevated,amino acid analysis suggested liver damage,and high amounts of dicarboxylic aciduria,low free carnitine,markedly increased long-chain acylcarnitine and hypoketotic hypoglycemia were also observed.His electrocardiogram showed atrioventricular block and ventricular tachycardia.After a series of treatments,including repeated electrical cardioversion,lidocaine and amiodarone for arrhythmia,arginine for blood ammonia level reduction,formula supplement containing L-carnitine and medium-chain fatty acid,the patient whose conditions had significantly improved and was discharged at the request of his parents at 29 days old.Two weeks later,he was re-admitted due to diarrhea,and discharged two days later when he was 45 days old.He was lost to follow up since then.(2) A homozygous mutation of c.199-10T＞G was detected in this boy in SLC25A20 gene,which was also carried by his parents.(3) Thirtytwo publications in English were retrieved,involving 50 cases of CACTD and 100 sequenced alleles.A total of 40 mutations in SLC25A20 gene were found so far,and c.199-10T＞G was the most common mutation with a frequency of 22/100.It was identified in 13 patients,including nine homozygous mutations and four compound heterozygous mutations.Symptoms presented within 72 h after birth (25 min-52 h) in all the 13 infants,such as hypoketotic hypoglycemia,hyperammonemia,elevated liver enzyme and creatine kinase,significantly decreased free carnitine level,markedly increased level of long-chain acylcarnitine,dicarboxylic aciduria,arrhythmia and cardiomyopathy.The mortality rate of CACTD was 11/12 (the outcome of one case was not reported).Conclusions c.199-10T＞G is the most common SLC25A20 gene mutation reported in Asia population with severe phenotypes and poor outcomes.Early diagnosis and timely treatment of CACTD are crucial.Inborn metabolic diseases such as CACTD should be considered if unexplainable exacerbation of clinical signs in neonatal period,or sudden infant death occurs.

El metabolismo del cobre. Sus consecuencias para la salud humana / Metabolism of copper. Its consequences for human health

Diversas enfermedades que constituyen problemas para la salud humana a nivel mundial, son el resultado de fallos en la homeostasis del cobre en la célula. El mecanismo de transporte del cobre no está completamente dilucidado; de ahí la necesidad de continuar profundizando en este tema. La presente revisión bibliográfica, sustentada en el análisis de 40 artículos científicos, describe los procesos de captación, distribución y eliminación del cobre en la célula; se refiere además a las enfermedades relacionadas con alteraciones en el metabolismo de dicho elemento y a su tratamiento, tales como, la enfermedad de Menkes y la de Wilson; y por último, a los estudios moleculares realizados en pacientes cubanos. Se concluye que el trabajo aporta información relevante que contribuye a la actualización y preparación del personal médico, respecto a estas afecciones a nivel molecular, celular y de organismo.

Several diseases which constitute a health problem for humans worldwide result from failure of copper cellular homeostasis. The mechanism of copper transportation in not completely defined therefore it is necessary to continue deepening on the topic. The present bibliographical review, based on the analysis of 40 scientific articles, describes the processes of copper catchment, distribution and elimination of copper in the cell; it refers, in addition to the diseases related to the metabolic disturbances of this element and its treatment, such as Menkes and Wilson diseases and lastly the molecular studies performed in Cuban patients. It is concluded that this work offers a significant information which contribute to the updating and preparation of the medical personnel regarding these illnesses at the molecular, cellular levels so as in the organism.

Analysis of four carnitine-acylcarnitine translocase deficiency cases caused by homozygous mutation of SLC25A20 c.199-10T> G / 中华儿科杂志

Objective@#To investigate the clinical, biochemical and genetic features of four carnitine-acylcarnitine translocase deficiency cases.@*Methods@#Four cases diagnosed with carnitine-acylcarnitine translocase deficiency from Guangxi Maternal and Child Health Hospital were studied. DNA was extracted from dry blood filter for gene analysis. SLC25A20 gene analysis was performed in 1 case and the whole exon sequence analysis was performed in 3 cases.@*Results@#Retrospective study on unrelated carnitine-acylcarnitine translocase deficiency patients, the age of onset was 1-28 d, the age of death were 1.5-30 d, main clinical features were hypoglycemia (4 cases), arrhythmia (2 cases), sudden death (2 cases). Biochemical test showed hypoglycemia (1.2-2.0 mmol/L) , elevated creatine kinase (955-8 361 U/L) and creatine kinase isozyme(199-360 U/L), normal or decreased free carnitine level (3.70-27.07 μmol/L) , elevated long-chain acylcarnitine (palmityl carnitine 1.85-14.84 μmol/L). The gene tests showed that all 4 cases carried SLC25A20 gene c.199-10T> G homozygous mutation, inherited from their parents. By analyzing the haplotype, we found that the mutation loci of C. 199-10T> G were all in the same haplotype.@*Conclusion@#The c.199-10T> G mutation is an important molecular cause of carnitine-acylcarnitine translocase deficiency, which has relatively high frequency in Guangxi population, and is related to the founder effect.

Preliminary application of Region 4 Stork project used in newborn screening by tandem mass spectrometry / 中华检验医学杂志

Objective To investigate the feasibility of Region 4 Stork(R4S)project used for newborn screening by tandem mass spectrometry in China.Methods This retrospective study was performed among 362 822 neonates screened by tandem mass spectrometry from May 2015 to April 2016 in Zhejiang newborn screening center.Infants were grouped by screening result category: 83 true positive cases,360 554 true negative cases and 2 185 false positive cases.Raw data was uploaded into R4S website to perform postanalytical interpretive tools, then results were analyzed with interpretation rules.The comparisons of normal population percentiles were done at five selected percentiles between Zhejiang newborn screening center and R4S project with min-max normalization.Results Compared with cutoff system by using R4S project with interpretation rules,the positive predictive value increased from 3.7%to 8.3%,the specificity increased from 99.40%to 99.75%, and the false positive rate declined from 0.6% to 0.2%. The two cases of true positive hyperprolinemia were reported negative, and one case of β-ketothiolase deficiency was misdiagnosis.Totally 311 638 cases in true negative group were resolved by postanalytical interpretive tools,and the remaining 48 916 cases were excluded with interpretation rules.False positive cases were reduced to 897 cases.Results of percentiles comparison showed that levels of some markers were significantly different between zhejiang newborn screening center and R 4S project.Conclusions R4S project effectively improved the newborn screening performance, whereas leaded to a small number of misdiagnosis and missed diagnosis.Besides,many true negative cases should be excluded with interpretation rules.Optimization should be achieved based on local normal population.(Chin J Lab Med,2018,41:300-304)