Clinicopathological features of hepatic fibrinogen storage disease in children / 中华病理学杂志

Objective: To investigate the clinicopathological and molecular characteristics of hepatic fibrinogen storage disease (FSD) in children. Methods: The clinical, histopathologic, immunophenotypic, ultrastructural and gene sequencing data of 4 FSD cases were collected from September 2019 to January 2021 in the Children's Hospital of Fudan University, Shanghai, China. Retrospective analysis and literature review were conducted. Results: There were 4 cases of FSD, 3 males and 1 female, aged 3 years and 3 months to 6 years (median age, 3 years and 4 months). The clinical manifestations were abnormal liver function and abnormal blood coagulation function, for which 2 cases had family genetic history. Liver biopsies revealed that, besides liver steatosis, fibrosis and inflammation, there were single or multiple eosinophilic inclusion bodies of various sizes and surrounding transparent pale halo in hepatocytes. Immunohistochemistry showed that the inclusion bodies were positive for anti-fibrinogen. Under the electron microscope, they corresponded to the dilated cisternae of the rough endoplasmic reticulum, which were occupied by compactly packed tubular structures and arranged into a fingerprint-like pattern with curved bundles. Gene sequencing revealed that the 2 cases of FGG mutation were located in exon 8 c.1106A>G (p.His369Arg) and c.905T>C (p.Leu302Pro), and 1 case was located in exon 9 c.1201C>T (p.Arg401Trp). No pathogenic variant was detected in the other case. Conclusions: FSD is a rare genetic metabolic disease and clinically manifests as abnormal liver function with hypofibrinogenemia. In the background of liver steatosis, fibrosis and inflammation, there are eosinophilic inclusions with pale halo in the hepatocytic cytoplasm, which can be identified by anti-fibrinogen immunohistochemical staining. The fingerprint-like structures under electron microscope are helpful for the diagnosis, while FGG sequencing detects the pathogenic mutation of exon 8 or 9 that can clearly explain the phenotype. However, the diagnosis of FSD cannot be completely ruled out if the relevant mutations are not detected.

Rare inherited kidney diseases: an evolving field in Nephrology / Doenças renais hereditárias raras: um campo em evolução na Nefrologia

Abstract There are more than 150 different rare genetic kidney diseases. They can be classified according to diagnostic findings as (i) disorders of growth and structure, (ii) glomerular diseases, (iii) tubular, and (iv) metabolic diseases. In recent years, there has been a shift of paradigm in this field. Molecular testing has become more accessible, our understanding of the underlying pathophysiologic mechanisms of these diseases has evolved, and new therapeutic strategies have become more available. Therefore, the role of nephrologists has progressively shifted from a mere spectator to an active player, part of a multidisciplinary team in the diagnosis and treatment of these disorders. This article provides an overview of the recent advances in rare hereditary kidney disorders by discussing the genetic aspects, clinical manifestations, diagnostic, and therapeutic approaches of some of these disorders, named familial focal and segmental glomerulosclerosis, tuberous sclerosis complex, Fabry nephropathy, and MYH-9 related disorder.

Resumo As doenças renais genéticas raras compreendem mais de 150 desordens. Elas podem ser classificadas segundo achados diagnósticos como (i) distúrbios do crescimento e estrutura, (ii) doenças glomerulares, (iii) tubulares e (iv) metabólicas. Nos últimos anos, houve uma mudança de paradigma nesse campo. Os testes moleculares tornaram-se mais acessíveis, nossa compreensão sobre os mecanismos fisiopatológicos subjacentes a essas doenças evoluiu e novas estratégias terapêuticas foram propostas. Portanto, o papel do nefrologista mudou progressivamente de mero espectador a participante ativo, parte de uma equipe multidisciplinar, no diagnóstico e tratamento desses distúrbios. O presente artigo oferece um panorama geral dos recentes avanços a respeito dos distúrbios renais hereditários raros, discutindo aspectos genéticos, manifestações clínicas e abordagens diagnósticas e terapêuticas de alguns desses distúrbios, mais especificamente a glomeruloesclerose segmentar e focal familiar, complexo da esclerose tuberosa, nefropatia de Fabry e doença relacionada ao MYH9.

NLRP3 inflammasome in metabolic syndrome

Metabolic syndrome (MS) is a serious health problem worldwide; it is characterized by a group of metabolic disorders, including central obesity, insulin resistance/type 2 diabetes, hyperlipidemia with accelerated atherosclerosis, hypertension, non-alcoholic fatty liver disease, and elevated uric acid with increased risk of gout. The incidence of MS has increased considerably in recent decades and has attracted considerable attention. A number of clinical and translational laboratory studies have implicated the activation of nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome in the development of MS, therefore establishing a strong link between chronic inflammation and metabolic diseases. This paper aims to review new developments on NLRP3 inflammasome in MS for better understanding of chronic inflammation in metabolic diseases. We will also provide new insights into using NLRP3 inflammasome as an innovative therapeutic target.

Pharmacogenetic implications in the management of metabolic diseases in Brazilian populations

Dyslipidemia, diabetes, obesity and hypertension are common metabolic diseases. In the last decades, unhealthy lifestyle and aging have leads to an increased incidence of these diseases, increasing morbidity and mortality by cardiovascular causes. The treatment of metabolic diseases includes life-style interventions as healthy diet and physical exercise, as well as pharmacological interventions. Several drugs are available for the management of metabolic diseases including among others lipid-lowering antidiabetics and antihypertensive drugs. Variability in response to these drugs is influenced by both genetic and non-genetic factors. Polymorphisms in genes related to drug pharmacokinetics and pharmacodynamics have been shown to influence drug efficacy and safety. This review is focused on pharmacogenetic studies related to the management of metabolic diseases in samples of the Brazilian population. Associations of variants in drug metabolizing enzymes and transporters, drug target and metabolism-related genes with the efficacy and safety of lipid-lowering, antidiabetic and antihypertensive drugs are described. Most pharmacogenetic studies in Brazil have focused in pharmacological response to a small group of drugs, as statins and some antihypertensives, while there are almost no studies on antidiabetic and antiobesity drugs. Some studies reported significant associations of gene polymorphisms with drug response confirming previous data from other populations, whereas other works did not replicate, which may relay on the genetic admixture of our population. In conclusion, further studies are necessary considering larger sample sizes, new unexplored drugs and more genetic variants to obtain stronger conclusions to explore clinical applications of pharmacogenetic studies in our population.

Polimorfismos del gen de apolipoproteína E y polimorfimo Pro12Ala del gen PPARy-2 en niños pre-puberes con factores de riesgo cardiometabólicos / Apolipoprotein E gene polymorphisms and Pro12Ala polymorfphism of PPARy-2 gene in children with risk factors to cardiometabolic disease

La resistencia a la insulina es muy frecuente en niños y adolescentes obesos, la cual conlleva a un significativo riesgo de desarrollar enfermedades cardiometabólicas causadas por la combinación de factores genéticos y factores asociados al estilo de vida. Evaluar la relación entre los polimorfismos del gen ApoE y el polimorfismo Pro12Ala del gen PPARγ2 en niños pre-púberes con factores de riesgo cardiometabólicos. Población y Métodos: Se evaluaron 141 niños (CANIA y Hospital “JM de los Ríos”), de los cuales 46 tienen obesidad, 33 hipercolesterolemia, 30 resistentes a la insulina (RI) y 32 controles. Se determinó colesterol total y fracciones, triglicéridos, glucosa, insulina e índice HOMA; se realizó extracción de ADN y análisis de los polimorfismos. La distribución de la frecuencia del alelo ε4 del gen de ApoE fue: 10,9% obesos, 7,6% hipercolesterolémicos, 18,3% RI y 4,6% controles. La frecuencia del polimorfismo Pro12Ala fue de 6,4% en la población estudiada. En los niños obesos e hipercolesterolémicos se observó aumento de colesterol total, LDL-c y triglicéridos asociados con la presencia del ε4; en el grupo con RI, se encontró que existen diferencias estadísticamente significativas entre el alelo ε4 con respecto al grupo control, lo que refiere que puede haber una relación clínica importante entre la presencia del alelo y el desarrollo de la enfermedad. No se encontró relación entre el polimorfismo Pro12Ala del gen PPARγ2 con factores de riesgo cardiometabólico. La presencia de varios polimorfismos en un mismo individuo podría estar asociada a factores de riesgo para enfermedad cardiometabólica

Insulin resistance (IR) is very frequent in children and adolescents obeses, which could contribute significantly in the development of cardiometabolic diseases, this could be associated to a combination of genetics factors and life’s style. Aim: To evaluate the relationship between ApoE gene polymorphisms and PPARγ2 gene Pro12Ala polymorphisms with risk factors to cardiometabolic disease in children. Population and Materials: 141 children (CANIA and Hospital “JM de los Ríos”), 46 with obesity, 33 with hypercholesterolemia, 30 with IR and 32 normal subjects. Total cholesterol and fractions, glucose, insulin and triglycerides were measured; also it was determinated the polymorphism genes on each patient. Results: The distribution of the frequency of the allele E4 of the ApoE gene were: 10, 9% obese, 7,6% hypercholesterolemia, 18,3% IR and 4,6% on normal subjects. The frequency of Pro12Ala polymorphism were up to 6,4% on the total subjects in the study. In the obese and hypercholesterolemic groups we found an increase of the total cholesterol, LDL-c and triglycerides, associated with the presence of allele ε4. In children with IR we got a significant difference of the presence of allele ε4 compared with the control group, which means that this allele could be related with the development of thedisease. It was not found a relation between the Pro12Ala of PPARγ2 gene and the development of obesity, hypercholesterolemia and insulin resistance in children. The presence of several polymorphisms in a same individual could be associated with risk factors to cardiometabolic disease

Estilo de vida e síndrome metabólica: exercício e tabagismo como moduladores da inflamação / Lifestyle and metabolic syndrome: exercise and smoking as modulators of inflammation

A inflamação subclínica é o elo entre a síndrome metabólica e as doenças crônicas, processo este agravado pela obesidade. Vários fatores de risco modificáveis têm sido associados com a inflamação, embora o efeito que cada um exerça, bem como o efeito acumulado destes fatores ainda não foi suficientemente explorado. Dentre os fatores modificáveis estão a atividade física e o tabagismo. Este trabalho revisa as recentes associações entre os biomarcadores inflamatórios e os fatores de risco modificáveis. Ainda, integra o conhecimento referente ao efeito modulador dos hábitos de vida nas concentrações dos biomarcadores inflamatórios e com isso prediz risco para as doenças crônicas e síndrome metabólica.

The low-grade inflammation is the link between metabolic syndrome and the chronic diseases, a process exacerbated by obesity. Several modifiable risk factors have been associated with inflammation, although the effect that each one carries, and the effect accumulated these factors has not been sufficiently explored. Among the modifiable risk factors are physical activity and smoking. This paper reviews the recent associations between inflammatory biomarkers and risk factors. Still, integrating the knowledge on the effect of the modulator lifestyle in the concentrations of inflammatory biomarkers and thereby predict risk for chronic diseases and acute metabolic.

Avaliação por imagem da área de gordura visceral e suas correlações com alterações metabólicas / Imaging assessment of visceral adipose tissue area and its correlations with metabolic alterations / Evaluación por imagen del área de grasa visceral y sus correlaciones con alteraciones metabólicas

FUNDAMENTO: A obesidade androgênica está associada a um risco maior de distúrbios metabólicos, favorecendo assim a ocorrência de doenças cardiovasculares e outras morbidades. OBJETIVO: Verificar a influência da área de tecido adiposo visceral (ATAV), medida pela tomografia computadorizada, sobre alterações metabólicas em adultos e idosos. MÉTODOS: Tomografias computadorizadas e valores de lipoproteínas: o colesterol total e frações, os triglicérides, a glicemia e o ácido úrico foram obtidos de 194 indivíduos estratificados por sexo, grupo etário e massa corporal, e analisados utilizando os testes de correlação e de média. RESULTADOS: Os idosos apresentaram maiores valores da ATAV, glicemia, ácido úrico e colesterol total. As maiores correlações foram encontradas entre a ATAV, os triglicérides e o VLDL-c (r > 0,5; p < 0,01), em ambos os grupos etários. A média da área de tecido adiposo visceral mostrou-se sempre mais elevada quando os valores de triglicérides e de glicemia estavam alterados, em ambos os grupos etários. CONCLUSÃO: A maioria dos exames apresentou forte correlação com a ATAV considerada de risco para alterações metabólicas. Em idosos, a área de tecido adiposo visceral de risco parece ser superior a de adultos.

BACKGROUND: Androgenic obesity is associated with a higher risk of metabolic disorders, thus favoring the occurrence of cardiovascular diseases and other morbidities. OBJECTIVE: To verify the influence of the visceral adipose tissue (VAT) area, measured by computed tomography (CT), on the metabolic alterations in adult and elderly individuals. METHODS: CT results and lipoprotein levels, total cholesterol and fractions, triglycerides, glycemia and uric acid levels, were obtained from 194 individuals stratified by sex, age group and body mass and analyzed using the tests of correlation and means. RESULTS: The elderly individuals presented higher VAT area, glycemia, uric acid and total cholesterol levels. The most important correlations were observed between VAT area, triglycerides (TG) and VLDL-c (r > 0.5; p < 0.01), in both age groups. The mean VAT area was always higher when TG and glycemia levels were altered, in both age groups. CONCLUSION: Most tests showed a strong correlation with VAT area, which was considered as risk for metabolic alterations. In elderly individuals, the risk VAT area seems to be higher than that of adult individuals.

FUNDAMENTO: La obesidad androgénica está asociada a un riesgo mayor de disturbios metabólicos, favoreciendo así la ocurrencia de enfermedades cardiovasculares y otras morbilidades. OBJETIVOS: Verificar la influencia del área de tejido adiposo visceral (ATAV), medida por la tomografía computarizada, sobre alteraciones metabólicas en adultos y adultos mayores. MÉTODOS: Tomografías computarizadas y valores de lipoproteínas: el colesterol total y fracciones, los triglicéridos, la glucemia y el ácido úrico se obtuvieron de 194 individuos estratificados por sexo, grupo de edad y masa corporal, y se analizaron utilizando las pruebas de correlación y de promedio. RESULTADOS: Los adultos mayores presentaron mayores valores de la ATAV, glucemia, ácido úrico y colesterol total. Las mayores correlaciones se encontraron entre la ATAV, los triglicéridos y el VLDL-c (r > 0,5; p < 0,01), en ambos grupos de edad. La media del área de tejido adiposo visceral se evidenció siempre más elevada cuando los valores de triglicéridos y de glucemia estaban alterados, en ambos grupos de edad. CONCLUSIÓN: La mayoría de los exámenes presentó fuerte correlación con la ATAV considerada de riesgo para alteraciones metabólicas. En adultos mayores, el área de tejido adiposo visceral de riesgo parece ser superior a la de adultos.

Adipokines and etiopathology of metabolic disorders

White adipose tissue is an endocrine organ producing numerous proteins known as adipokines, which include leptin, adiponectin, resistin, visfatin, and other factors, which are involved in most metabolic disorders. In obesity, plasma leptin concentrations are high due to leptin resistance that may result from the attenuation of leptin signaling in the hypothalamus. Leptin acts to inhibit appetite, stimulate thermogenesis, enhance fatty acid oxidation, decrease glucose, and reduce body weight, and fat. A reduced adiponectin level has been associated with insulin resistance, dyslipidemia, and atherosclerosis, and its low level is a predictor of later development of type 2 diabetes. Resistin expression is low in adipose tissue and high in bone marrow and lungs, its role in glucose homeostasis remains controversial, it has been associated with insulin resistance and obesity. Visfatin is a secretory protein highly enriched in visceral adipocytes, liver, muscle, and lymphocytes. An increase of visfatin levels in obesity was related to preservation of insulin sensitivity, it enhances glucose uptake by adipocytes and inhibits hepatocyte glucose release, it induces tyrosine phosphorylation, and interacts with insulin receptors. Many studies are still being conducted to highlight the role of adipokines in metabolic disorders

Biomarcadores séricos del estado de salud en jóvenes universitarios de acuerdo a su nivel de actividad física / Serum biomarkers of health status in university students according to their level of physical activity

El objetivo del estudio fue categorizar el riesgo a sufrir enfermedades cardiometabólicas a partir del uso de biomarcadores del metabolismo de los lípidos y proteínas en estudiantes deportistas o sedentarios de la Universidad Central de Venezuela. Se determinó en suero de 103 sujetos (55 deportistas y 48 sedentarios), por método colorimétrico: creatinina (Cr), proteína total (Pt), albúmina (Al), triglicéridos (Tg), colesterol total (Col-T), y lipoproteínas de alta densidad (HDL-C), mientras que la de baja densidad (LDL-C) se obtuvo por la fórmula de Friedewald y las globulinas por la resta entre Pt y Al. Los niveles séricos de los biomarcadores se encontraron dentro de los rangos de referencia. Sólo en las HDL-C y las globulinas no se observaron diferencias significativas entre sedentarios y deportistas. En estos últimos se consiguieron los Tg notablemente bajos, mientras que el Col-T fue alto, principalmente a expensa de la LDL-C. En este grupo, la condición de los diferentes componentes del perfil lipídico y del índice Col-T/HDL-C estuvieron influenciadas por una distorsión transitoria de la lipemia, posiblemente asociada a procesos inflamatorios mediados por respuesta inmune que se presenta en actividad física de alta intensidad. Se detectó baja proporción de HDL-C elevado en sedentarios y deportistas. Apenas 2,1 por ciento de los sedentarios y 1,0 por ciento de la muestra total tuvieron albúmina sérica baja, la cual está asociada a riesgo incrementado a sufrir enfermedades cardiovasculares (ECV). Una pequeña proporción de la muestra evaluada pudiera ser susceptible a sufrir algún tipo de enfermedad cardiometabólica

The main objective of this study was to categorize the risk of suffering of cardiometabolic disease. For this, lipids and proteins metabolic biomarkers were used on sporting or sedentary students from Universidad Central de Venezuela. The following parameters were determined by colorimetric methods: Creatinine (Cr), Total protein (Tp), Albumin (Al), Triglycerides (Tg), Total cholesterol (T-Cho) and High density lipoproteins (HDL-C). The low density lipoproteins (LDL-C) were calculated by using the Friedewald formulae and globulins values were obtained by subtracting Tp from Al. The seric biomarkers levels were in the normal reference ranges. There were not significant differences on the HDL-C and globulins values between sporting and sedentary students. The sporting group showed very low Tg levels, with high T-Cho, due mainly to LDL-C. In this group, the conditions of the different components of the lipidic profile and T-Cho/HDL-C rate were influenced by a transitory lipemic distortion, possibly due to inflammatory mechanism mediated by immune response, which is observed in physical activity of high intensity. Low levels of HDL-C were obtained from both studied groups. Only 2,1 percent from the sedentary group and 1,0 percent of total sample showed low levels of albumin, which is associated to high risk of suffering from cardiovascular disease. Only a small part of the evaluated sample could be susceptible of suffering cardiometabolic disease

Síndrome metabólica em pacientes hipertensos atendidos ambulatoriamente em um hospital de ensino / Metabolic syndrome in hypertensive patients seen in an outpatient teaching hospital / Síndrome metabólico en pacientes hipertensos vistos en un hospital de enseñanza ambulatoria

Objetivo do estudo foi investigar a prevalência da síndrome metabólica (SM) e sua relação com estágios da hipertensão arterial (HA) em hipertensos da Clínica de Hipertensão do Hospital das Clínicas-UFPE, entre 1996-2006. Trata-se de estudo observacional transversal, com 802 hipertensos selecionados de 1264, sendo 73,6% mulheres. A SM foi identificada segundo critério da International Diabetes Federation e a HA classificada pelas V Diretrizes Brasileiras Hipertensão. Foram analisadas variáveis socioeconômicas e prováveis associações entre SM e estágios da HA, utilizando testes qui-quadrado e Mann-Whitney (p<0,05). Observou-se alta prevalência de SM na amostra (68,6%), predominante nas mulheres (53,0%; p<0,01) e nas faixas etárias de 50-69 anos (38,8%) p>0,05. A renda per capita e escolaridade, com concentração da amostra nos níveis mais baixos (44,6 e 51,8% respectivamente), mostraram tendência regular decrescente e similar nos portadores (p<0,05) ou não (p>0,05) de SM. Notou-se uma elevada frequência da amostra no grupo com três componentes da SM (31,8%), obesidade abdominal (83,3%) e hiperglicemia (51,1%). Na categorização da PA, verificou-se uma concentração da amostra (68,4%) e dos indivíduos com (47,2%) ou sem SM (21,2%), no estágio 3 da HA. A SM não apresentou correlação positiva com os estágios da HA (p>0,05); somente com a pressão diastólica (PAD), sendo p<0,05. Concluindo-se, a prevalência de SM foi de 68,6%, com maior concentração no estágio 3 da HA e em mulheres. A não associação entre SM e estágios da HA diverge de achados da literatura. Entretanto, a correlação significativa entre PAD e SM corrobora de investigações recentes.

Study aimed to investigate the prevalence of metabolic syndrome (MS) and its relation to stages of hypertension (HA) in hypertensive patients of the Hypertension Clinic, Hospital das Clinicas-UFPE, between 1996-2006. This is an observational cross-sectional study with 802 hypertensive patients screened in 1264, and 73.6% women. MS was diagnosed with criteria of the International Diabetes Federation and hypertension classified by the V Brazilian Guidelines Hypertension. Socioeconomic variables were analyzed and possible associations between MS and stages of hypertension, using chi-square and Mann-Whitney test (p <0.05). There was a high prevalence of MS in the sample (68.6%), predominantly in women (53.0% p <0.01) and in the age groups 50-69 years (38.8%) p> 0, 05. The per capita income and schooling, with the sample concentration at lower levels (44.6% and 51.8% respectively) showed regular trend of decreasing and similar in patients (p <0.05) or not (P> 0, 05) SM. We noticed a high frequency of the sample in the group with three components of metabolic syndrome (31.8%), abdominal obesity (83.3%) and hyperglycemia (51.1%). In the categorization of the PA, there was a concentration of the sample (68.4%) and individuals (47.2%) or without SM 921.2%), stage 3 hypertension. SM did not show positive correlation with the stages of hypertension (p> 0.05) only with diastolic blood pressure (DBP), and p <0.05. Concluding, the prevalence of MS was 68.6%, with greater concentration in the third stage of hypertension and in women. The lack of association between MS and stages of hypertension differs from findings in the literature. However, the significant correlation between DBP and SM corroborates recent research.

Objetivo fue investigar la prevalencia del síndrome metabólico (SM) y su relación con los estadios de la hipertensión arterial (HA) en los pacientes hipertensos Clínica de Hipertensión en el Hospital de Clínicas-UFPE, entre 1996-2006. Este es un estudio observacional transversal con 802 pacientes hipertensos controlados en 1264, y las mujeres 73,6%. MS fue diagnosticado con criterios de la Federación Internacional de Diabetes y la hipertensión clasificados por las Directrices V brasileña hipertensión. Las variables socioeconómicas fueron analizadas y las posibles asociaciones entre los Estados miembros y las etapas de la hipertensión, el uso de chi-cuadrado y la prueba de Mann-Whitney (p <0,05). Hubo una elevada prevalencia de SM en la muestra (68,6%), prevalente en las mujeres (53,0%, p <0,01) y la edad de 50-69 años (38,8%) p> 0, 05. El ingreso per cápita y la escolarización, con la concentración de la muestra en los niveles inferiores (44,6% y 51,8% respectivamente), mostraron tendencia decreciente de regular y similar en pacientes (p <0,05) o no (p> 0, 05) SM. Nos dimos cuenta de una alta frecuencia de la muestra en el grupo con tres componentes del síndrome metabólico (31,8%), obesidad abdominal (83,3%) y la hiperglucemia (51,1%). Categorización de la PA, había una concentración de la muestra (68,4%) e individuos (47,2%) o sin EM 921,2%), etapa 3 la hipertensión. SM no muestra correlación con las etapas de la hipertensión (p> 0,05) sólo con la presión diastólica (PAD), y p <0,05. En conclusión, la prevalencia de SM fue del 68,6%, con una mayor concentración en la tercera fase de la hipertensión y en las mujeres. La falta de asociación entre la EM y etapas de la hipertensión se diferencia de los hallazgos en la literatura. Sin embargo, la correlación significativa entre el DBP y el SM corrobora las investigaciones recientes.

Alteraçöes vestibulares em doenças metabólicas que afetam o sistema nervoso central / Vestibular disorders in metabolic diseases affecting the central nervous system

O objetivo deste trabalho foi verificar sinais de afecção do sistema vestibular central de diversas etiologias, através da vectoeletronistagmografia em cinco pacientes cuja faixa etária variou de 50 a 73 anos de idade sendo três do sexo feminino e dois do sexo masculino. O nistagmo semi-espontâneo (unidirecional, bidirecional e múltiplo) foi o sinal mais comumente encontrado, sendo que os outros sinais centrais foram muito variáveis de caso para caso.

Diagnóstico de doenças metabólicas do sistema nervoso da infância por exame ultra-estrutural de tecido näo cerebral / Diagnosis of metabolic diseases of nervous system in children through ultrastructural analysis of non cerebral tissue

Se bem que as análises bioquímica e de genética molecular sejam os métodos mais precisos para o diagnóstico de doenças metabólicas, os estudos morfológicos permanecem um método diagnóstico muito importante principalmente em países como o Brasil, onde os laboratórios clínicos nao estao aptos a realizar a maior parte dos exames requeridos para o reconhecimento destas doenças. Ainda, o exame anátomo-patológico é o único método diagnóstico para certas doenças cujo defeito metabólico é desconhecido tais como as lipofuscinoses ceróides, a distrofia neuroaxonal infantil e a doença de Lafora. Apresentamos nossa experiência com análise ultra-estrutural em 582 exames de conjuntiva ocular (n=320), pele (n=92) ou nervo periférico (n=170) realizados entre 1975 e 1996, em 486 crianças. Em 112 casos, o exame revelou-se anormal. Em 59, o exame ultra-estrutural isoladamente fez o diagnóstico. Em 29 casos, o exame foi menos específico, tendo o diagnóstico final sido feito através da combinaçao da análise clínica e patológica. Nos 24 casos restantes, o diagnóstico genérico de uma mucopolissacaridose foi feito em 8 casos, de oligossacaridose em 4 e o de gangliosidose GM2 em 8. Sempre que a análise bioquímica pôde ser procedida, o diagnóstico ultra-estrutural foi confirmado. Estes resultados sublinham a importância do exame ultra-estrutural em tecidos nao cerebrais em muitas doenças metabólicas, sobretudo quando testes bioquímicos nao podem ser realizados.

Patologías Endocrinas y metabólicas: diabetes mellitus, hipotiroidismo, hiperplasia suprarrenal congenita / Endocrine diseases and metabolic: diabetes mellitus, hypothyroidesm, adrenal hyperplasia congenital

Las anormalidades de la diferenciación sexual y el desarrollo, siempre en combinación con hipertensión o pérdida de sal, son los marcados clínicos de la Hiperplasia Suprarrenal Congénita. El diagnóstico debe hacerse tan rápido como sea posible, con el propósito de iniciar el tratamiento y detener los efectos de la anomalía enzimática. El diagnóstico y una decisión racional en la asignación del sexo dependerá de la determinación del sexo genético, la determinación hormonal de la enzima deficiente y de la valoracción del potencial del paciente para su actividad sexual futura y fertilidad. Es necesario y urgente que el médico reconozca, en el recién nacido, los signos clínicos de ambiguedad genital así como la pérdida de sal, característicos de la HSC, y refiera estos pacientes al endocrinólogo pediatra para una evaluación completa. En caso de que esta evaluación no sea posible hacerla en forma inmediata, sugerimos tomar una muestra de sangre al paciente (aproximadamente 8 cc. sin anticoagulante) centrifugarla y guardar el suero congelado e iniciar el tratamiento substitutivo, para luego gestionar la consulta con el especialista. Recordemos que el diagnóstico precoz conlleva a la instauración del tratamiento adecuado, que corregirá los síntomas específicos causados por la deficiencia enzimática que, junto con el control adecuado, resultará en un crecimiento y desarrollo normales del paciente