Immediate adverse events to intravenous immunoglobulin in pediatric patients with inborn errors of immunity: A longitudinal study with a pre-infusion protocol

Introduction Immunoglobulin represents the main therapy for patients with inborn errors of immunity (IEI) and it is a safe procedure, but adverse events (AEs) can occur with variable frequencies. Objective To evaluate the frequency of immediate AEs to intravenous immunoglobulin (IVIG) regular therapy in a pediatric cohort with IEI after a pre-IVIG infusion protocol. Methods This was a longitudinal study from 2011 to 2019 at a tertiary pediatric hospital in Brazil. Results A total of 1736 infusions were studied in 70 patients with IEI, 46 (65.7%) of whom were males and whose median age was 5.8 years old (range: 6 mo - 18 yo). Seven different brands of IVIG were used with the median loading dose of 0.57g/kg (range: 0.23 - 0.88g/Kg). According to the protocol, pre-medication and step-up infusion rate, were performed in 1305 (75.2%) infusions. Immediate AEs were noted in 10 children (14.3%) and in 22 (1.2%) infusions. Skin reactions (rash or urticaria) were the most common AE with 14 episodes (0.8% of all infusions). Almost all AEs were mild (19/86.4%), with no severe ones being observed. The majority of the AEs (81.8%) was identified at a 0.04ml/kg/min infusion rate. Gender, age at first infusion, presence of infection on the infusion day and change of the IVIG brand were evaluated and none of them were associated with AEs. Conclusion The low frequency of immediate AEs in children with IEI highlights the safety and tolerability of intravenous immunoglobulin replacement with the procedures established at our center.

Compounded drugs as an alternative to the therapeutical gaps of inborn errors of metabolism

Abstract Inborn errors of metabolism are rare disorders with few therapeutic options for their treatments, which can make patients suffer with complications. Therefore, compounded drugs might be a promising option given that they have the ability of meeting the patient's specific needs, (i) identification of the main drugs described in the literature; (ii) proposal of compounding systems and (iii) calculation of the budgetary addition for the inclusion of these drugs into the Brazilian Unified Health System. The research conducted a literature review and used management data as well as data obtained from official Federal District government websites. The study identified 31 drugs for the treatment of inborn errors of metabolism. Fifty eight percent (58%) (18) of the medicines had their current demand identified, which are currently unmet by the local Health System. The estimated budget for the production of compounded drugs was of R$363,16.98 per year for approximately 300 patients. This estimated cost represents a budgetary addition of only 0.17% from the total of expenditures planned for drug acquirement. There is a therapeutic gap for inborn errors of metabolism and compounding pharmacies show potential in ensuring access to medicine therapy with a low-cost investment.

Imunizações em pacientes com doenças raras ­ Posicionamento conjunto da Sociedade Brasileira de Imunizações (SBIm), Associação Brasileira de Alergia e Imunologia (ASBAI) e Sociedade Brasileira de Pediatria (SBP) / Immunizations in patients with rare diseases ­ A joint position statement of the Brazilian Society of Immunizations (SBIm), Brazilian Association of Allergy and Immunology (ASBAI), and Brazilian Society of Pediatrics (SBP)

Introdução: De acordo com a Organização Mundial da Saúde, a prevalência de doenças raras (abaixo de 65 casos/100.000 habitantes) é de 6%, e variável na dependência da população em estudo. Há 6.172 doenças raras (DR) catalogadas. Esquemas vacinais específicos para DR não estão disponíveis no Brasil, e esta orientação é limitada na maioria dos países. Objetivos: Identificar e propor esquemas específicos de imunização para pacientes com DR, tendo-se em conta segurança e eficácia. Fonte de dados: Revisão não sistemática da literatura, com busca de artigos de 2000 a 2020 no PubMed, Google Scholar, SciELO e Orphanet usando os termos "rare diseases" ou "inborn errors of metabolism" ou "cystic fibrosis" ou "inborn errors of immunity" e "vaccines" ou "immunization" ou "vaccination", nos idiomas inglês, francês, espanhol e português. Conclusões: A imunização de pessoas com DR é tema complexo, com poucas recomendações publicadas a este respeito, e na maioria das vezes realizada de modo empírico. É importante que a equipe médica que acompanha esses pacientes tenha um olhar abrangente e proporcione a prevenção mais completa possível.

Background: According to the World Health Organization, the prevalence of rare diseases (below 65 cases/100 000 population) is 6% and may vary depending on the study population. There are 6172 rare diseases (RD) listed. RD-specific vaccine schemes are not available in Brazil, and guidance is limited in most countries. Objectives: To identify and propose specific immunization schemes for RD patients, valuing safety and efficacy. Data source: A nonsystematic literature review was conducted, with search for articles from 2000 to 2020 on PubMed, Google Scholar, SciELO, and Orphanet with the terms "rare diseases" or "inborn errors of metabolism" or "cystic fibrosis" or "inborn errors of immunity" and "vaccines" or "immunization" or "vaccination," in English, French, Spanish, and Portuguese languages. Conclusions: Immunization of RD patients is a complex topic with few published recommendations, most often produced empirically. The medical teams following up these patients should have a more comprehensive insight and provide the most complete prevention possible.

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.

Hypoadiponectinemia as a marker of increased cardiovascular risk in patients with non-alcoholic fatty liver disease: correlation with albumin/creatinine ratio

ABSTRACT Objective: We assessed plasma adiponectin and its correlation with carotid intima-media-thickness (CIMT), as a marker of atherosclerosis, and urine albumin/creatinine ratio (ACR) in patients with non-alcoholic fatty liver disease (NAFLD). Subjects and methods: The study included 100 Egyptian subjects (50 patients with NAFLD with no history of diabetes or hypertension and 50 age and sex-matched normal healthy control subjects). Urine albumin/creatinine ratio (ACR) was assessed in all participants and fasting plasma adiponectin was measured using ELISA technique. Ultrasonography was used to diagnose NAFLD. CIMT was assessed using high-resolution Doppler ultrasonography. Results: Mild albuminuria was detected in patients with NAFLD (mean urine ACR = 42 ± 30 mg/g). Plasma adiponectin was significantly lower and urine ACR and CIMT significantly higher in patients with NAFLD as compared with the control group (P < 0.001 for all). A significant negative correlation was found between plasma adiponectin and both urine ACR and CIMT in patients with NAFLD (P < 0.001 and < 0.05 respectively). A significant positive correlation was also found between CIMT and urine ACR in those patients (P < 0.05). Plasma adiponectin and urine ACR were independent determinants of CIMT in patients with NAFLD (P < 0.01 and < 0.05 respectively). Conclusion: Patients with NAFLD, without diabetes, have an increased risk of atherosclerosis and cardiovascular disease. Hypoadiponectinemia and low-grade albuminuria are important markers of that risk.

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.

Positive improvement in palatability of metabolic formula with the use of miraculin protein in patients with inborn errors of metabolism and healthy adults / Cambio positivo en la palatabilidad de la fórmula metabólica con el uso de la proteína miraculina en pacientes con errores innatos del metabolismo y adultos sanos

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.

Errores innatos metabólicos en parálisis cerebral: estudio en 174 infantes / Inborn errors of metabolism in 174 cases of cerebral palsy

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)

Programación fetal / Fetal programming

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)

Importancia de una propuesta para la implementación de un programa de tamizaje neonatal expandido en Colombia / Importance of a Proposal for Implementing an Expanded Neonatal Screening Program in Colombia / Importância de uma proposta para a implementação de um programa de triagem neonatal ampliada na colômbia

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.

Caracterización fenotípica y genotipica de la deficiencia de glucosa-6-fosfato deshidrogenasa en Argentina: Estudio retrospectivo y descriptivo / Phenotypic and genotypic characterization of glucose-6-phosphate dehydrogenase deficiency in Argentina: Retrospective and descriptive study

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.

Changes in temporomandibular joint anatomy, changes in condylar translation, and their relationship with disc displacement: magnetic resonance imaging study / Ressonância magnética das alterações anatômicas e translação condilar da articulação temporomandibular e suas relações com o deslocamento do disco

Abstract Objective: To assess changes in the articular surfaces of the temporomandibular joint (TMJ) and in condylar translation, as detected by magnetic resonance imaging (MRI), determining whether such changes correlate with disc displacement. Materials and Methods: We retrospectively analyzed the MRI scans of 2076 TMJs of 1038 patients with symptoms of temporomandibular disorder. We attempted to determine whether articular disc deformity and changes in condylar translation, as well as changes in the articular surfaces of the condyle, glenoid fossa, and articular eminence, correlated with disc displacement. Results: Disc displacement with reduction was associated with changes in the shape of the articular eminence. Disc displacement without reduction was most strongly associated with disc deformity, condylar degeneration, glenoid fossa degeneration, and effusion. Neither decreases nor increases in condylar translation were associated with disc deformity, degenerative bone changes, or disc displacement. Conclusion: Changes in the shape of the articular eminence seem to predispose to progression of internal derangement of the TMJ.

Resumo Objetivo: Verificar a correlação entre as alterações das superfícies articulares e da translação condilar com o deslocamento de disco da articulação temporomandibular. Materiais e Métodos: Foram analisados os exames de ressonância magnética de 2076 articulações temporomandibulares de pacientes sintomáticos de desordens temporomandibulares. A deformidade do disco articular, as alterações nas superfícies articulares do côndilo, da fossa glenoide e da eminência articular e as alterações na translação condilar foram correlacionadas com o deslocamento do disco. Resultados: O deslocamento do disco com redução demonstrou associação com as alterações de forma da eminência articular. O deslocamento do disco sem redução apresentou maior associação com a deformidade do disco, degeneração do côndilo e da fossa glenoide e efusão. Diminuição e aumento da translação condilar não apresentaram associação com a deformidade do disco, com alterações ósseas degenerativas, nem com o deslocamento do disco. Conclusão: Mudanças na forma da eminência articular parecem predispor à progressão do desarranjo interno da articulação temporomandibular.

Repercussions of inborn errors of immunity on growth / Repercussões dos erros inatos da imunidade sobre o crescimento

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.

Trastornos psiquiátricos secundarios a enfermedades neurometabólicas / Psychiatric Disorders Secondary to Neurometabolic Disorders

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.

Colestasis por deficiencia de 3β-Δ5-C27-hidroxiesteroide deshidrogenasa en un paciente con alteración en la síntesis de ácidos biliares / Cholestasis due to deficiency of 3β-Δ5-C27-hydroxysteroid dehydrogenase in a patient with altered bile acid synthesis

Resumen: Introducción: Los errores innatos en la síntesis de ácidos biliares son un grupo de defectos genéticos que representan del 1 al 2% de las enfermedades colestásicas crónicas en lactantes, niños y adolescentes. La deficiencia de 3β-Δ5-C27-hidroxiesteroide oxidoreductasa (3β-HSDH) es el defecto más comúnmente reportado. El cuadro clínico característico consiste en hepatitis neonatal, hepatomegalia, esplenomegalia, malabsorción, desnutrición y enfermedad hepática de aparición tardía. Caso clínico: Lactante masculino con antecedente de ictericia en escleras a los 4 meses que se resolvió espontáneamente; posteriormente, a los 18 meses, presentó enfermedad colestásica. Durante su abordaje se documentó gamma-glutamil transpeptidasa normal, hallazgo que es altamente sugestivo de alteración en la síntesis de ácidos biliares. El diagnóstico se realizó con espectrometría de masas en orina. Se inició tratamiento con ácido cólico oral, y presentó mejoría inmediata. Conclusiones: El resultado en los ácidos biliares urinarios es definitivo para el defecto genético y consistente con mutaciones homocigotas en el gen HSD3B7. Este padecimiento constituye un diagnóstico de exclusión en las enfermedades colestásicas de la infancia, particularmente el hallazgo de gamma-glutamil transpeptidasa normal o levemente aumentada, y responde adecuadamente al tratamiento oral, por lo que debe identificarse de forma temprana.

Abstract: Background: Inborn errors in bile acid synthesis are a group of genetic defects accounting for 1 to 2% of chronic cholestatic diseases in infants, children and adolescents. Deficiency of 3β-Δ5-C27-hydroxysteroid dehydrogenase (3β-HSDH) is the most common defect in this disease. Clinical features consist of neonatal hepatitis, hepatomegaly, splenomegaly, malabsorption, malnutrition, and late-onset liver disease. Case report: A male infant who presented jaundice in sclera at 4 months that resolved spontaneously, later presented cholestatic disease at 18 months. During his approach, normal gamma-glutamyl transpeptidase was documented, a finding that is highly suggestive of alteration in the synthesis of bile acids. The diagnosis was made using urine mass spectrometry. Oral colic acid treatment was started, presenting immediate improvement. Conclusions: The result in urinary bile acids is definitive for the genetic defect and consistent with homozygous mutations in the HSD3B7 gene. This condition is a diagnosis of exclusion in childhood cholestatic diseases, particularly in the presence of normal or mildly enlarged gamma-glutamyl transpeptidase, and responds adequately to oral treatment; it should be identified early.