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Arch. argent. pediatr ; 119(1): e41-e44, feb. 2021. tab, ilus
Article in Spanish | LILACS, BINACIS | ID: biblio-1147256


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.

Humans , Male , Child , Desensitization, Immunologic/methods , Enzyme Replacement Therapy , Mucopolysaccharidosis II/drug therapy , Hypersensitivity, Immediate , Metabolism, Inborn Errors
Article in Chinese | WPRIM | ID: wpr-879569


OBJECTIVE@#To explore the clinical and genetic characteristics of a child with MEGDEL syndrome.@*METHODS@#Clinical data of the child was reviewed. Peripheral blood samples of the child and his parents were collected. Mitochondrial genome and the whole exome of the child were analyzed by next-generation sequencing. Candidate variants and its origin were verified by Sanger sequencing and fluorescence quantitative PCR.@*RESULTS@#The patient, a 2-year-and-6-month-old male, has featured hypoglycemia, mental and motor retardation with regression. Cranial MRI showed bilateral putamen damage suggestive of Leigh syndrome. Testing of urine organic acid indicated that the level of 3-methylpentenoic acid was slightly increased. Whole exome sequencing revealed that the child has harbored heterozygous deletion of exons 6 to 17 and c.307A>T nonsense variant of the SERAC1 gene, which were respectively inherited from his parents who were asymptomatic. Treatment with Levocarnitine, vitamin B1, vitamin B2, coenzyme Q10, baclofen and glucuronolactone resulted in improvement of sleep and mental state.@*CONCLUSION@#A case of MEGDEL syndrome without deafness was diagnosed. Discovery of the nonsense mutation and large fragment deletion have enriched the spectrum of SERAC1 gene variants.

Child, Preschool , Hearing Loss, Sensorineural/genetics , Humans , Leigh Disease , Male , Metabolism, Inborn Errors/genetics , Molecular Biology , Mutation
Chinese Journal of Surgery ; (12): 179-191, 2021.
Article in Chinese | WPRIM | ID: wpr-878277


Pediatric liver transplantation (PLT) is an effective strategy of treating various acute or chronic end-stage liver diseases and inherited metabolic diseases in children.PLT has been applied in many transplant centers nationwide and has achieved satisfactory results.However,the development of transplant centers is uneven,and there is a lack of consensus and standards within the industry.In order to reduce post-operative complications,accelerate post-operative recovery,and improve the short-and long-term quality of life of children,the Enhanced Recovery After Surgery Committee of Chinese Research Hospital Association organized multidisciplinary experts to summarize the progress of domestic and international research,and formulated a perioperative consensus on PLT based on the principles of evidence-based medicine.The consensus provides recommendations for perioperative PLT from three aspects:preoperative assessment and preparation,intraoperative management and postoperative management,in order to provide reference guidelines for centers that are conducting or preparing to conduct PLT.

Child , Consensus , End Stage Liver Disease/therapy , Enhanced Recovery After Surgery/standards , Humans , Liver Transplantation/standards , Metabolism, Inborn Errors/therapy , Perioperative Care/standards , Practice Guidelines as Topic
Rev. Paul. Pediatr. (Ed. Port., Online) ; 39: e2020095, 2021. tab, graf
Article in English, Portuguese | LILACS | ID: biblio-1155476


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.

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/epidemiology
Rev. chil. nutr ; 47(5): 801-807, set. 2020. tab, graf
Article in English | LILACS | ID: biblio-1138617


ABSTRACT As palatability of medical formulas has been documented as unpleasant, new options are required to improve acceptance and adherence in people with inborn errors of metabolism (IEM). Miracle fruit (Synsepalum dulcificum) has a glycoprotein named miraculin that transforms a sour, bitter taste such as the one found in metabolic formula, into a sweet perception. The objective of this work is to analyze the response in the taste perception of metabolic formula with the use of the miraculin tablets in patients with IEM and healthy adults. To test this hypothesis a prospective, longitudinal, quasi-experimental, analytical study was performed. Patients with IEM and healthy adults were recruited. All participants assessed 3 different liquids (lemon, apple cider vinegar and metabolic formula) before and after the administration of miraculin tablets and completed a questionnaire. The sensory responses were evaluated using hedonic scales, analyzed with nonparametric tests for paired data. Seven patients with IEM and 14 healthy subjects were included. After miraculin intake 57% of patients (Z ≤ -1.89 p= 0.059) and healthy adults (Z≤ -2.31 p= 0.021) had a positive change in their taste perception. The absolute frequency of patients who did not like the metabolic formula decreased from 4 to 1, and in patients who liked it or loved, it increased from 0 to 2 and from 0 to 1 respectively; the frequency of patients who perceived the metabolic formula as indifferent or hated it, did not change. Response in taste perception had a positive change of 57% in both groups. The use of miraculin tablets may improve palatability of metabolic formula.

RESUMEN La palatabilidad de las fórmulas médicas se ha reportado como desagradable, se requieren nuevas opciones para mejorar la aceptación en personas con errores innatos del metabolismo (EIM). La fruta milagrosa (Synsepalum dulcificum) contiene una glucoproteína llamada miraculina que transforma el sabor agrio y amargo en dulce. El objetivo fue analizar la respuesta en la percepción del sabor de la fórmula metabólica con el uso de las tabletas de miraculina en pacientes con EIM y adultos sanos. Se realizó un estudio analítico prospectivo, longitudinal, cuasi-experimental. Los participantes evaluaron la percepción de 3 líquidos (limón, vinagre de manzana y fórmula metabólica) antes y después de la administración de tabletas de miraculina y completaron un cuestionario. Las respuestas sensoriales se evaluaron mediante escalas hedónicas, analizadas con pruebas no paramétricas para datos pareados. Se incluyeron 7 pacientes con EIM y 14 adultos sanos. Después de la miraculina el 57% de los pacientes (Z ≤ -1,89 p= 0,059) y adultos sanos (Z≤ -2,31 p= 0,021) tuvieron un cambio positivo en su percepción del sabor. La frecuencia absoluta de pacientes a los que no les gustó la fórmula disminuyó de 4 a 1, y en quienes les gustó o les encantó, aumentó de 0 a 2 y de 0 a 1 respectivamente; la frecuencia de los pacientes que percibieron la fórmula como indiferente u odiada, no cambió. La respuesta en la percepción del sabor cambió positivamente en el 57% en ambos grupos. El uso de miraculina puede mejorar la palatabilidad de la fórmula metabólica.

Adolescent , Adult , Biotransformation , Synsepalum , Taste Perception , Fruit , Amino Acids , Metabolism, Inborn Errors
Revista Digital de Postgrado ; 9(2): 214, ago. 2020.
Article in Spanish | LILACS, LIVECS | ID: biblio-1103446


El término Origen Temprano de las Enfermedades del Adulto explica la aparición temprana de las condiciones anormales cardiovasculares y metabólicas en la vida adulta, mayor riesgo de morbilidad y muerte asociados a factores ambientales, especialmente nutricionales, que actúan en las primeras etapas de la vida. Estas respuestas programadas dependen de la naturaleza del estímulo o noxa, del tiempo de exposición y del momento de ocurrencia de la noxa, pudiendo un solo genotipo original varios fenotipos y estarían condicionadas por criterios críticos en los cuales se desarrollarían cambios a largo plazo pudiendo ser reversibles o no. La Programación Fetal explica que respuestas adaptativas embrionarias y fetales en un ambiente subóptimo genera consecuencias adversas permanentes. La desnutrición, así como la sobrenutrición fetal aumenta el riesgo de desarrollar alteraciones en el peso y composición corporal fetal, y posteriormente obesidad, síndrome metabólico, incremento en la adiposidad, alteración en el metabolismo de la glucosa y / o insulina, alteración del metabolismo lipídico, alteraciones hepáticas y de las cifras tensionales. La impronta genómica es esencial para el desarrollo y defectos en la misma puede originar alteraciones de la identidad parental transmisibles a las siguientes generaciones. Esta programación fetal puede ser explicada por la epigenética, definida como la serie de alteraciones hereditarias de la expresión genética a través de modificaciones del ADN y las histonas centrales sin cambios en la secuencia de ADN. Estas modificaciones epigenéticas alteran la estructura y condensación de la cromatina, afectando la expresión del genotipo y fenotipo. Este artículo desarrolla los aspectos involucrados en la Programación Fetal y los posibles mecanismos sobre la misma(AU)

The term Early Origin of Adult Diseases explains the early onset of abnormal cardiovascular and metabolic conditions in adult life, increased risk of morbidity and death associated with environmental factors, especially nutritional factors, that act in the early stages of life. These programmed responses depend on the nature of the stimulus or noxa, the time of exposure and the moment of occurrence of the noxa, with a single original genotype being able to have several phenotypes and would be conditioned by critical criteria in which long-term changes could develop, reversibles or not. Fetal Programming explains that embryonic and fetal adaptive responses in a suboptimal environment generate permanent adverse consequences. Fetal malnutrition as overnutrition increases the risk of developing alterations in fetal body weight and composition, and subsequently obesity, metabolic syndrome, increased adiposity, impaired glucose and / or insulin metabolism, impaired lipid metabolism, liver disorders and altered blood pressure. The genomic imprint is essential for development and defects in it can cause alterations of the parental identity and are transmitted to the following generations. This fetal programming can be explained by epigenetics, defined as the series of inherited alterations of genetic expression through modifications of DNA and central histones without changes in the DNA sequence. These epigenetic modifications alter the structure and condensation of chromatin, affecting the expression of the genotype and phenotype. This article develops the aspects involved in Fetal Programming and the possible mechanisms on it(AU)

Humans , Fetal Nutrition Disorders , Fetal Development , Noxae , Nutritional and Metabolic Diseases , Body Composition , Hypothalamus/anatomy & histology , Metabolism, Inborn Errors
Revista Digital de Postgrado ; 9(2): 205, ago. 2020. tab
Article in Spanish | LILACS, LIVECS | ID: biblio-1102879


La Parálisis Cerebral (PC) es un conjunto de alteraciones motrices no progresivas en la población infantojuvenil, ocasionadas por lesión ­a nivel cerebral- de neuronas o fibras de esa vía, de sus aferencias o de las que la modulan; para su diagnóstico deben conocerse otras patologías también frecuentes y que pueden incidir simultánea o causalmente en la motricidad del paciente; la resultante sería disfunción motora tanto voluntaria como involuntaria, refleja o con propósito, de la postura y/o del tono muscular. Objetivo: detectar errores innatos metabólicos (EIM) que causan o se asocian con PC en una serie significativa. Métodos: Estudio descriptivo-interpretativo, se revisaron los expedientes clínicos del Centro de Parálisis Cerebral de Caracas, en cuyos diagnósticos se presentaron ambas alteraciones, entre los años 1988 y 2018. Resultados: De las 2.000 historias clínicas revisadas, el exámen clínico y las pruebas de laboratorio permitieron seleccionar 174 casos de EIM. Conclusiones: Se tipificaron los errores innatos metabólicos en diez formas clínicas distintas, se evidenciaron en pacientes con PC atendidos en un centro público de Caracas, es posible que la casuística sea varias veces mayor en Venezuela dado que ya no se aplica la pesquisa en los centros de atención pública(AU)

Cerebral Palsy (CP) is a set of non-progressive motor alterations in the child and youth population, caused by injury - at the brain level - of neurons or fibers of that pathway, their afferences or those that modulate it; for its diagnosis, other pathologies that are also frequent and that can simultaneously or causally affect the motor skills of the same patient must be known; The result would be both voluntary and involuntary motor dysfunction, reflected or with purpose, of posture and / or muscle tone. Objective: to detect inborn metabolic errors (EIM) that cause or are associated with CP in a significant series. Methods: Descriptive-interpretive study, we reviewed the clinical records of the Cerebral Palsy Center of Caracas, in whose diagnoses both alterations were presented, between the years 1988 and 2018. Results: Of the 2,000 clinical histories reviewed, the clinical examination and tests Laboratory tests allowed the selection of 174 cases of IMD. Conclusions: Inborn metabolic errors were typified in ten different clinical forms, they were evidenced in patients with CP treated in a public center in Caracas, it is possible that the casuistry is several times greater in Venezuela since the investigation is no longer applied in the centers of public attention(AU)

Humans , Male , Female , Child, Preschool , Child , Adolescent , Cerebral Palsy/pathology , Metabolism, Inborn Errors , Neurons/metabolism , Pediatrics , Nervous System Diseases
Article in Chinese | WPRIM | ID: wpr-828310


OBJECTIVE@#To analyze the clinical and genetic characteristics of an infant girl featuring comprehensive developmental backwardness.@*METHODS@#The patient was subjected to clinical examination, gas chromatography mass spectrometry and next-generation sequencing (NGS).@*RESULTS@#The child was insensitive to sound, could not turn over, raise head, laugh or recognize his mother. Laboratory tests were all normal, but metabolic analysis suggested 3-methylglutaconic aciduria due to elevated 3-methylglutaconic acid and 3-methylglutaric acid. NGS has detected two compound heterozygous CLPB variants in the child, namely c.1085G>A and c.1700A>C, which were respectively inherited from her father and mother. Bioinformatic analysis predicted both variants to be pathogenic. The patient was diagnosed with 3-methylglutaconic aciduria type VII (MGCA7).@*CONCLUSION@#The MGCA7 in the child was probably caused by CLPB gene variants. NGS has provided a powerful diagnostic tool for this rare disorder.

Endopeptidase Clp , Genetics , Female , Genetic Testing , High-Throughput Nucleotide Sequencing , Humans , Infant , Metabolism, Inborn Errors , Genetics
Article in Chinese | WPRIM | ID: wpr-879475


OBJECTIVE@#To analyze the molecular etiology of a Chinese child affected with dihydropyrimidinase deficiency.@*METHODS@#Genomic DNA was extracted from peripheral blood samples of the family members. Pathogenic variant was determined by whole exome sequencing and verified by Sanger sequencing.@*RESULTS@#The child was found to harbor homozygous c.905G>A (p.Arg302Gln) variants in exon 5 of the DPYS gene, for which her parents were both heterozygous carriers.@*CONCLUSION@#The homozygous c.905G>A (p.Arg302Gln) variants of the DPYS gene probably underlies the dihydropyrimidinase deficiency in the child. Above result has enabled genetic counseling and prenatal diagnosis for this family.

Amidohydrolases/genetics , Asians/genetics , Child , Exons , Female , Humans , Metabolism, Inborn Errors/genetics , Mutation , Pedigree
Rev. MED ; 27(2): 21-33, jul.-dic. 2019. tab, graf
Article in Spanish | LILACS | ID: biblio-1115226


Resumen: El tamizaje neonatal expandido permite la detección temprana de diversos errores innatos del metabolismo. En Colombia, las condiciones para llevar adelante un programa nacional de alto impacto en salud pública están dadas. A través de una búsqueda bibliográfica sobre el tema en diferentes países, se realizó una disertación sobre la implementación de un programa nacional de tamizaje neonatal. Esto con el fin de plantear una propuesta de tamizaje neonatal expandido por espectrometría de masas en tándem en Colombia, completo, conciso, detallado y acorde con la legislación colombiana, las necesidades y las características de la población. Implementar un programa nacional de este tipo supone un gran impacto en la salud pública y debe ser liderado por el Estado, con la participación y apoyo de profesionales de salud, academia, asociaciones de pacientes e industria farmacéutica.

Abstract: Expanded neonatal screening allows early detection of various inborn errors of metabolism. In Colombia, the conditions to carry out a national program with a high impact on public health are in place. Through a review of the international literature on the subject, this reflection on the implementation of a national neonatal screening program brings forward a complete, concise, detailed proposal for tandem mass spectrometry-expanded neonatal screening in Colombia that conforms to the legislation and the needs and characteristics of the population. Implementing such a national program has a great impact on public health and must be led by the State, with the participation and support of health professionals, academia, patient associations, and the pharmaceutical industry.

Resumo: A triagem neonatal ampliada permite que vários erros inatos do metabolismo sejam identificados precocemente. Na Colômbia, as condições para a realização de um programa nacional com alto impacto na saúde pública estão disponíveis. Por meio de uma pesquisa bibliográfica sobre o assunto em diferentes países, foi realizada uma dissertação sobre a implementação de um programa nacional de triagem neonatal. A fim de apresentar uma proposta de triagem neonatal ampliada por espectrometria de massas em tandem na Colômbia, completa, concisa, detalhada e de acordo com a legislação colombiana, as necessidades e as características da população. A implementação de um programa nacional desse tipo tem um grande impacto na saúde pública e deve ser liderada pelo Estado, com a participação e o apoio de profissionais da saúde, da academia, das associações de pacientes e da indústria farmacêutica.

Humans , Neonatal Screening , Public Health , Genetic Diseases, Inborn , Metabolism, Inborn Errors
Arch. argent. pediatr ; 117(4): 267-270, ago. 2019. tab
Article in English, Spanish | LILACS, BINACIS | ID: biblio-1054935


La deficiencia de glucosa-6-fosfato deshidrogenasa es la enzimopatía eritrocitaria causada por mutaciones en el gen G6PD, cuya herencia está ligada al cromosoma X. Se analizan las características clínicas y de laboratorio de 24 individuos con deficiencia de G6PD durante 25 años. La edad mediana al momento del diagnóstico fue 10,2 años (rango: 0,6-56,4). El 54,2 % de los pacientes fueron asintomáticos, mientras que el 25 % presentó anemia hemolítica crónica no esferocítica; el 12,5 %, ictericia neonatal y anemia hemolítica posinfecciones, y el 8,3 %, anemia hemolítica aguda pos ingesta de habas. Los 24 pacientes estudiados presentaron variantes descritas previamente en la literatura. Las características clínicas observadas estuvieron acordes con las variantes encontradas. Veintiuna mujeres, pertenecientes a la rama materna de los individuos afectados, pudieron ser identificadas por biología molecular como portadoras de la deficiencia, por lo que recibieron el consejo genético correspondiente.

Glucose-6-phosphate dehydrogenase deficiency is an erythrocyte enzyme disorder caused by mutations in the G6PD gene, which has an X-linked inheritance. Here we analyze the clinical and laboratory characteristics of 24 subjects with G6PD deficiency over 25 years. Their median age at diagnosis was 10.2 years (range: 0.6-56.4). No symptoms were observed in 54.2 % of patients, whereas 25 % had chronic non-spherocytic hemolytic anemia; 12.5 %, neonatal jaundice and postinfectious hemolytic anemia; and 8.3 %, acute hemolytic anemia after ingestion of fava beans. The 24 studied patients had variants that had been previously described in the bibliography. The clinical characteristics observed here were consistent with the variants found. A total of 21 women from the maternal line of affected subjects were identified as deficiency carriers using molecular biology techniques, so they received the corresponding genetic counseling.

Humans , Male , Female , Child , Diagnosis , Glucosephosphate Dehydrogenase Deficiency , Metabolism, Inborn Errors , Molecular Biology
J. pediatr. (Rio J.) ; 95(supl.1): S49-S58, 2019. tab, graf
Article in English | LILACS | ID: biblio-1002472


Abstract Objectives: This study aimed to review the literature on the repercussions of the different inborn errors of immunity on growth, drawing attention to the diagnosis of this group of diseases in patients with growth disorders, as well as to enable the identification of the different causes of growth disorders in patients with inborn errors of immunity, which can help in their treatment. Data sources: Non-systematic review of the literature, searching articles since 2000 in PubMed with the terms "growth", "growth disorders", "failure to thrive", or "short stature" AND "immunologic deficiency syndromes", "immune deficiency disease", or "immune deficiency" NOT HIV. The Online Mendelian Inheritance in Man (OMIN) database was searched for immunodeficiencies and short stature or failure to thrive. Data summary: Inborn errors of immunity can affect growth in different ways, and some of them can change growth through multiple simultaneous mechanisms: genetic syndromes; disorders of the osteoarticular system; disorders of the endocrine system; reduction in caloric intake; catabolic processes; loss of nutrients; and inflammatory and/or infectious conditions. Conclusions: The type of inborn errors of immunity allows anticipating what type of growth disorder can be expected. The type of growth disorder can help in the diagnosis of clinical conditions related to inborn errors of immunity. In many inborn errors of immunity, the causes of poor growth are mixed, involving more than one factor. In many cases, impaired growth can be adjusted with proper inborn errors of immunity treatment or proper approach to the mechanism of growth impairment.

Resumo Objetivos: Revisão da literatura sobre as repercussões dos diferentes erros inatos da imunidade sobre o crescimento, chamar a atenção para o diagnóstico desse grupo de doenças em pacientes que apresentem desordens do crescimento, assim como permitir que se identifiquem as diferentes causas de alterações do crescimento em pacientes com erros inatos da imunidade, o que pode auxiliar em seu manejo. Fonte dos dados: Revisão não sistemática da literatura, com busca de artigos desde 2000 no Pubmed com os termos "growth" ou "growth disorders" ou "failure to thrive" ou "short stature" AND "immunologic deficiency syndromes" ou "immune deficiency disease" ou "imune deficiency" NOT HIV. E buscas na base OMIN (Online Mendelian Inheritance in Man) por imunodeficiências e baixa estatura ou falha no crescimento ("failure to thrive"). Síntese dos dados: Há diferentes modos pelos quais os erros inatos da imunidade podem afetar o crescimento e alguns deles podem alterar o crescimento por múltiplos mecanismos simultâneos: síndromes genéticas; afecções do aparelho osteoarticular; afecções do sistema endócrino; redução de aporte calórico; processos catabólicos: perda de nutrientes, assim como afecções inflamatórias e/ou infecciosas. Conclusões: O tipo de erros inatos da imunidade permite prever que tipo de alteração no crescimento devemos esperar. O tipo de alteração no crescimento pode auxiliar no diagnóstico de condições clínicas associadas aos erros inatos da imunidade. Em muitos erros inatos da imunidade, as causas do crescimento deficiente são mistas, envolvem mais de um fator. Em muitos casos, o prejuízo do crescimento pode ser corrigido com o adequado tratamento dos erros inatos da imunidade ou adequada abordagem do mecanismo que causa o prejuízo do crescimento.

Humans , Growth Disorders/etiology , Immunologic Deficiency Syndromes/complications , Metabolism, Inborn Errors/complications , Immunologic Deficiency Syndromes/classification , Metabolism, Inborn Errors/classification
Article in Chinese | WPRIM | ID: wpr-776787


OBJECTIVE@#To assess the value of dry blood spot tandem mass spectrometry for the diagnosis of autism spectrum disorder (ASD).@*METHODS@#Peripheral blood samples of 277 autistic children were collected. Their amino acid and carnitine profiles were detected by liquid chromatography tandem mass spectrometry. Urine samples of suspected patients were collected for verification by gas chromatography mass spectrometry. Blood samples were also taken for genetic testing.@*RESULTS@#Of the 277 children with ASD, 19 (6.9%) were suspected to be with inborn error of metabolism (IEM), which included 6 cases with amino acidemia, 9 with organic acidemia and 4 with fatty acidemia. Three cases of phenylketonuria, one case of homocysteinemia, one case of propionemia, one case of methylmalonic acidemia, one case of glutaric acidemia, one case of isovaleric acidemia, one case of argininemia, one case of citrullinemia I and four cases of primary carnitine deficiency were confirmed by genetic testing, which yielded an overall diagnostic rate of 5.1% (14/277).@*CONCLUSION@#Our result has provided further evidence for the co-occurrence of ASD and IEM. Tandem mass spectrometry has a great value for the diagnosis and treatment of ASD in childhood.

Amino Acid Metabolism, Inborn Errors , Diagnosis , Autism Spectrum Disorder , Diagnosis , Child , Dried Blood Spot Testing , Gas Chromatography-Mass Spectrometry , Humans , Metabolism, Inborn Errors , Diagnosis , Tandem Mass Spectrometry
Article in Chinese | WPRIM | ID: wpr-776745


OBJECTIVE@#To determine the incidence and mutational types of fatty acid oxidation disorders (FAOD) in central-northern region of Guangxi.@*METHODS@#A total of 62 953 neonates were screened for FAOD during December 2012 and December 2017. Acyl-carnitine profiling of neonatal blood sample was performed by tandem mass spectrometry using dry blood spots on a filter paper. The diagnosis of FAOD was confirmed by organic acid profiling of urea and genetic testing.@*RESULTS@#Eighteen cases of FAOD were diagnosed among the 62 953 neonates. Among these, primary carnitine deficiency (PCD) was the most common type (n=13), which was followed by short-chain acyl-CoA dehydrogenase deficiency (SCADD) (n=2), medium-chain acyl-CoA dehydrogenase deficiency (MCADD) (n=1), multiple acyl-CoA dehydrogenase deficiency (MADD) (n=1), and carnitine palmitoyltransferase II deficiency (CPT II D) (n=1). Genetic testing has revealed two previously unreported variants, i.e., c.337G to A (p.Gly113Arg) of ACADS gene and c.737G TO T (p.Gly246Val) of ETFA gene.@*CONCLUSION@#PCD is the most common FAOD in central-northern Guangxi. Tandem mass spectrometry combined with genetic testing may facilitate early diagnosis of FAOD.

Acyl-CoA Dehydrogenase , Genetics , Carnitine , Blood , Carnitine O-Palmitoyltransferase , China , Electron-Transferring Flavoproteins , Genetics , Humans , Infant, Newborn , Lipid Metabolism, Inborn Errors , Diagnosis , Genetics , Metabolism, Inborn Errors , Diagnosis , Multiple Acyl Coenzyme A Dehydrogenase Deficiency , Diagnosis , Neonatal Screening , Tandem Mass Spectrometry
Article in Chinese | WPRIM | ID: wpr-775043


OBJECTIVE@#To establish a congenital chloride diarrhea (CCD)-associated SLC26A3 c.392C>G (p.P131R) polymorphism-expressing cell model, and to investigate its biological function.@*METHODS@#The sequence of the SLC26A3 gene in GenBank was used to design the upstream and downstream single-guide RNA (sgRNA) that could specifically recognize the 392 locus of the SLC26A3 gene, and the sgRNA was mixed with the pSpCas9-puro vector after enzyme digestion to construct an eukaryotic recombinant expression plasmid (pSpCas9-SLC26A3). Caco-2 cells were transfected with the recombinant plasmid and synthesized single-stranded DNA oligonucleotides (ssODNs), and Taqman genotyping assay and Sanger sequencing were used to identify the expression of SLC26A3 c.392C>G (p.P131R) in Caco-2 cells. Wild-type Caco-2 cells were selected as normal control group and the Caco-2 cells with successful expression of SLC26A3 c.392C>G (p.P131R) was selected as P131R group. Both groups were treated with 100 ng/mL tumor necrosis factor-α (TNF-α), and then the normal control group was named as TNF-α group, and the P131R group was named as TNF-α+P131R group. Electric cell-substrate impedance sensing (ECIS) assay was used to evaluate the change in the monolayer barrier function of intestinal epithelial cells in the above four groups, and Western blot was used to measure the change in the expression of SLC26A3 protein in the normal control group and the P131R group.@*RESULTS@#The eukaryotic recombinant expression plasmid (pSpCas9-SLC26A3) was successfully constructed. Both Taqman genotyping assay and Sanger sequencing confirmed the successful establishment of the Caco-2 cell model of SLC26A3 c.392C>G (p.P131R) expression. ECIS assay showed that compared with the normal control group, the P131R group had a significant increase in the monolayer permeability of intestinal epithelial cells (PG (p.P131R) can reduce the expression of SLC26A3 protein, increase the monolayer permeability of intestinal epithelial cells, and thus lead to diarrhea.

Caco-2 Cells , Chloride-Bicarbonate Antiporters , Genetics , Diarrhea , Genetics , Humans , Intestinal Mucosa , Metabolism, Inborn Errors , Genetics , Polymorphism, Single Nucleotide , Sulfate Transporters , Genetics , Tight Junctions , Tumor Necrosis Factor-alpha
Yonsei Medical Journal ; : 1061-1066, 2019.
Article in English | WPRIM | ID: wpr-762053


PURPOSE: Newborn screening (NBS) programs are important for appropriate management of susceptible neonates to prevent serious clinical problems. Neonates admitted to neonatal intensive care units (NICU) are at a potentially high risk of false-positive results, and repetitive NBS after total parenteral nutrition is completely off results in delayed diagnosis. Here, we present the usefulness of a targeted next-generation sequencing (TNGS) panel to complement NBS for early diagnosis in high-risk neonates. MATERIALS AND METHODS: The TNGS panel covered 198 genes associated with actionable genetic and metabolic diseases that are typically included in NBS programs in Korea using tandem mass spectrometry. The panel was applied to 48 infants admitted to the NICU of Severance Children's Hospital between May 2017 and September 2017. The infants were not selected for suspected metabolic disorders. RESULTS: A total of 13 variants classified as likely pathogenic or pathogenic were detected in 11 (22.9%) neonates, including six genes (DHCR7, PCBD1, GAA, ALDOB, ATP7B, and GBA) associated with metabolic diseases not covered in NBS. One of the 48 infants was diagnosed with an isobutyl-CoA dehydrogenase deficiency, and false positive results of tandem mass screening were confirmed in two infants using the TNGS panel. CONCLUSION: The implementation of TNGS in conjunction with conventional NBS can allow for better management of and earlier diagnosis in susceptible infants, thus preventing the development of critical conditions in these sick infants.

Complement System Proteins , Delayed Diagnosis , Diagnosis , Early Diagnosis , Humans , Infant , Infant, Newborn , Intensive Care Units, Neonatal , Korea , Mass Screening , Metabolic Diseases , Metabolism, Inborn Errors , Oxidoreductases , Parenteral Nutrition, Total , Tandem Mass Spectrometry
Article in English | WPRIM | ID: wpr-741368


Hyperammonemia can be caused by several genetic inborn errors of metabolism including urea cycle defects, organic acidemias, fatty acid oxidation defects, and certain disorders of amino acid metabolism. High levels of ammonia are extremely neurotoxic, leading to astrocyte swelling, brain edema, coma, severe disability, and even death. Thus, emergency treatment for hyperammonemia must be initiated before a precise diagnosis is established. In neonates with hyperammonemia caused by an inborn error of metabolism, a few studies have suggested that peritoneal dialysis, intermittent hemodialysis, and continuous renal replacement therapy (RRT) are effective modalities for decreasing the plasma level of ammonia. In this review, we discuss the current literature related to the use of RRT for treating neonates with hyperammonemia caused by an inborn error of metabolism, including optimal prescriptions, prognosis, and outcomes. We also review the literature on new technologies and instrumentation for RRT in neonates

Ammonia , Astrocytes , Brain Edema , Coma , Diagnosis , Edema , Emergency Treatment , Humans , Hyperammonemia , Infant, Newborn , Metabolism , Metabolism, Inborn Errors , Peritoneal Dialysis , Plasma , Prescriptions , Prognosis , Renal Dialysis , Renal Replacement Therapy , Urea
Rev. colomb. psiquiatr ; 47(4): 244-251, oct.-dic. 2018.
Article in Spanish | LILACS, COLNAL | ID: biblio-978329


Hay algunas enfermedades secundarias a errores innatos del metabolismo que se asocian a trastornos psiquiátricos o síntomas neurológicos menores. La existencia de algunos pacientes con signos únicamente psiquiátricos representa un desafío diagnóstico y terapéutico. El objetivo del presente artículo es describir 6 enfermedades neurometabólicas tratables que se presentan con síntomas psiquiátricos que camuflan su origen orgánico, con el propósito de que se las tome en cuenta en la consulta psiquiátrica. Se describen los trastornos del metabolismo de la homocisteína y del ciclo de la urea, la enfermedad de Wilson, la enfermedad de Niemann-Pick tipo C, la porfiria aguda y la xantomatosis cerebrotendinosa. El análisis de la literatura lleva a proponer una lista de síntomas psiquiátricos asociados con dichas afecciones, que abarcan desde los cambios insidiosos del afecto y el curso del pensamiento hasta síntomas atípicos, como alucinaciones visuales, efectos paradójicos de los medicamentos antipsicóticos y trastornos del comportamiento de niños y adolescentes que conllevan degradación de la autonomía. Asimismo se listan los signos neurológicos más frecuentemente relacionados, como las alteraciones del estado de conciencia, los trastornos de la conducta motora y el equilibro, la catatonia o el déficit cognitivo progresivo. Se hace hincapié en la importancia de considerar la resistencia al tratamiento antipsicótico como una señal importante para sospechar organicidad y la mejoría significativa de la alteración psiquiátrica cuando se instaura un tratamiento eficaz y precoz.

Some diseases secondary to inborn errors of metabolism are associated with psychiatric, disorders or minor neurological symptoms. The existence of some cases with exclusively psychiatric symptoms represents a diagnostic and therapeutic challenge. The aim of this article is to describe seven treatable neurometabolic disorders that should be taken into account in the psychiatric consultation as they manifest with psychiatric symptoms that mask the organic origin of the disorder. Homocysteine metabolism and urea cycle disorders, Wilson's disease, Niemann-Pick disease Type C, acute porphyria and cerebrotendinous xanthomatosis are described. Following an analysis of the literature, a list of psychiatric symptoms associated with these disorders are proposed, ranging from insidious changes in affective state and thought to atypical symptoms such as visual hallucinations, as well as paradoxical effects of antipsychotics or behavioural disorders in children and adolescents associated with loss of autonomy. The most frequently associated neurological signs, such as alterations in the state of consciousness, motor behaviour and balance disorders, catatonia or progressive cognitive deficit are also listed. Emphasis is placed on the importance of considering resistance to antipsychotic treatment as a warning sign to suspect organicity, as well as the significant improvement in psychiatric impairment when effective and early treatment is established.

Humans , Child , Adolescent , Mental Disorders , Metabolism , Metabolism, Inborn Errors , Antipsychotic Agents , Niemann-Pick Diseases , Porphyria, Acute Intermittent , Consciousness , Xanthomatosis, Cerebrotendinous , Personal Autonomy , Diagnosis , Urea Cycle Disorders, Inborn , Hallucinations , Homocysteine