Trastornos adquiridos y congénitos de la deficiencia de vitamina B12 en niños / Acquired and inherited disorders of vitamin B12 deficiency in children

Vitamin B12 is an essential micronutrient for cell growth and the development of the central nervous system. Its deficiency can manifest clinically as megaloblastic anemia, peripheral neuropathy, myelopathy and neuropsychiatric disorders. Early detection and treatment are essential as it can cause irreversible neurological sequelae. Diagnosis is often challenging as it is based on clinical and biochemical features. Clinically, the symptoms are nonspecific and equivocal. Biochemically, there is no gold standard to detect Cobalamin deficiency. The available biomarkers do not have a defined cut-off value or are not sensitive or specific enough. This article exposes the different causes of vitamin B12 deficiency, analyzes the advantages and disadvantages of biochemical markers and, for the first time, proposes an algorithmic diagnosis using biomarkers and therapeutic tests. The ultimate goal is to alert pediatricians to the difficulties of diagnosing vitamin B12 deficiency and strategies are proposed to differentiate between acquired and congenital cobalamin conditions. Finally, the treatment according to the etiology is described in a practical manner, as well as the expected time for improvement of the biochemical parameters.

La vitamina B12 es un micronutriente fundamental para el crecimiento celular y el desarrollo del sistema nervioso central. Su deficiencia puede manifestarse clínicamente como anemia megaloblástica, neuropatía periférica, mielopatía y trastornos neuropsiquiátricos. La detección y el tratamiento tempranos son esenciales, ya que esta deficiencia puede generar secuelas neurológicas irreversibles. El diagnóstico suele ser un desafío, ya que se basa en pilares clínicos y bioquímicos. Clínicamente, los síntomas son inespecíficos y equívocos. Bioquímicamente no existe un gold standard para diagnosticar la deficiencia de cobalamina. Los biomarcadores existentes no presentan un valor de corte definido o no son lo suficientemente sensibles o específicos. Este trabajo expone las diferentes causas de deficiencia de vitamina B12, analiza las ventajas y desventajas de los marcadores bioquímicos y por primera vez se plantea un algoritmo diagnóstico mediante biomarcadores y pruebas terapéuticas. El objetivo último es alertar a los pediatras acerca las dificultades que representa el diagnóstico de deficiencia de vitamina B12 y se proponen estrategias para diferenciar cuadros adquiridos versus congénitos de la deficiencia de cobalamina. Por último, se describe de manera práctica el tratamiento según la etiología así como el tiempo esperado para la mejoría de los parámetros bioquímicos.

Polineuropatia diabética assintomática induzida pelo uso crônico de metformina e correlação com vitamina B12 / Asymptomatic diabetic polyneuropathy induced by chronic metformin use and correlation with vitamin B12

Introdução: Diabetes Mellitus é doença metabólica, caracterizada pela deficiência absoluta ou relativa de insulina, que acomete cerca de 382 milhões de pessoas em todo mundo, tendo uma das complicações mais comuns a polineuropatia. A Metformina, medicamento amplamente utilizado como tratamento do Diabetes, foi descrita como responsável, em algumas literaturas, por causar ou agravar deficiência de vitamina B12, que está similarmente relacionada ao desenvolvimento de polineuropatia.Métodos: Nesse sentido, foi conduzido um estudo no município de Soledade ­ RS, com objetivo de verificar se essa relação é condizente com a realidade da localidade. Foram escolhidos 58 pacientes, dos quais 30 responderam questionários adaptados baseados na literatura e na Classificação de Neuropatia de Michigan (MNSS-Brasil), então colhidos 5 ml de sangue venoso da fossa antecubital, preparado soro do qual uma alíquota foi separada para determinação bioquímica da vitamina B12.Resultados: Analisando os resultados, a maioria dos pacientes analisados apresentou sintomas de polineuropatia, e 10% deste, deficiência vitamínica.Conclusão: nenhuma variável explicou a correlação do uso crônico da Metformina, dose e gênero com a deficiência da vitamina B12, o que indica que não há evidências fortes o suficiente que sustentem esse fato, de acordo com as particularidades da localidade analisada.

Introduction: Diabetes Mellitus is a metabolic disease, characterized by absolute or relative insulin deficiency, which affects about 382 million people, with polyneuropathy being one of the most common complications. Metformin, a drug widely used as a treatment for diabetes, has been described as responsible, in some literature, for causing or aggravating vitamin B12 deficiency, which is similarly related to the development of polyneuropathy.Methods: In this sense, a study was conducted in Soledade ­ RS, in order to verify whether this relationship is consistent with the reality of the locality. Fifty-eight patients were selected, of which 30 answered adapted questionnaires based on the literature and on the Michigan Neuropathy Classification (MNSS-Brazil), then 5 ml of venous blood was collected from the antecubital fossa, serum prepared from which an aliquot was separated for biochemical determination of the vitamin B12.Results: Analyzing the results, most of these patients presented symptoms of polyneuropathy and, 10% of them, vitamin deficiency.Conclusion: no variable explained the correlation of chronic use of Metformin, dose and gender with vitamin B12 deficiency, which indicates that there is not enough evidence to support this fact, according to the particularities of the analyzed locality.

Diferentes formas de presentación de la anemia megaloblástica en el lactante / Different forms of presentation of megaloblastic anemia in the infant

Introducción: La anemia megalobástica es un trastorno madurativo de los precursores eritroides y mieloides causado por déficit de vitamina B12, ácido fólico, o ambos. Es poco común en la infancia y su prevalencia se desconoce por ser una enfermedad poco frecuente. Objetivo: Describir diferentes formas de presentación de la anemia megaloblástica en el lactante. Presentación de casos: Se presentan dos casos de lactantes, en el caso 1 la madre tuvo una alimentación precaria durante el embarazo y la lactancia, prolongó la lactancia materna exclusiva más de 6 meses. La paciente comenzó a perder las habilidades ganadas en el desarrollo psicomotor y presentó trastornos neurológicos graves, por lo que se consideró que se trataba de una enfermedad progresiva del sistema nervioso central. En el caso 2, en el que se prolongó la lactancia materna exclusiva, apareció trombocitopenia, por lo que se sospechó una enfermedad hematológica maligna. Resultados: En ambos casos después de realizar diversas pruebas para descartar enfermedades neurológicas (caso 1) y enfermedades hematológicas (caso 2) se diagnosticó anemia megaloblástica por déficit de vitamina B12 por disminución en la ingesta y una reserva limítrofe en la madre que lacta. En ambos casos los síntomas desaparecieron con el tratamiento vitamínico sustitutivo. Conclusiones: En el lactante la anemia megaloblástica se puede presentar de diferentes formas clínicas a pesar de tener la misma causa, un déficit en la ingesta y una reserva escasa de la madre durante el embarazo y lactancia(AU)

Introduction: Megaloblastic anemia is a maturing disorder of the erythroid and myeloid precursors caused by deficiency of vitamin B12, folic acid, or both. It is uncommon in childhood and its prevalence is unknown because it is a rare disease. Objective: To describe different forms of presentation of megaloblastic anemia in infants. Presentation of cases: Two cases of infants are presented, in case 1 the mother had a precarious diet during pregnancy and lactation, and prolonged exclusive breastfeeding more than 6 months. The patient began to lose the skills gained in psychomotor development and presented severe neurological disorders, so it was considered that it was a progressive disease of the central nervous system. In case 2, in which exclusive breastfeeding was prolonged, thrombocytopenia appeared, so a malignant hematological disease was suspected. Results: In both cases, after performing various tests to rule out neurological diseases (case 1) and hematological diseases (case 2), megaloblastic anemia was diagnosed due to vitamin B12 deficiency due to a decrease in intake and a borderline reserve in the breastfeeding mother. In both cases the symptoms disappeared with vitamin replacement therapy. Conclusions: In the infant, megaloblastic anemia can occur in different clinical ways despite having the same cause, a deficit in intake and a low reserve of the mother during pregnancy and lactation(AU)

La asociación del déficit de vitamina B12 y metformina / The association of vitamin B12 deficiency and metformin

La metformina es el agente antidiabético oral más utilizado para el tratamiento de la diabetes mellitus tipo 2 (DM2) y se ha descrito la asociación de su uso con el déficit de vitamina B12. Se realizó una revisión narrativa de estudios para conocer la evidencia de dicha asociación, y las recomendaciones para su pesquisa, prevención y tratamiento. La prevalencia informada del déficit de vitamina B12 en los pacientes tratados con metformina osciló entre el 5,8% y el 52% en las diferentes series. Los pacientes de mayor edad, aquellos que reciben metformina a altas dosis y por más tiempo, y los que no consumen alimentos de origen animal, son quienes presentan mayor riesgo de padecer este déficit. Se recomienda la determinación de vitamina B12 cada año en pacientes con DM2 tratados con metformina y la eventual reposición en caso de déficit. Si bien existe consenso sobre el tratamiento del déficit, aún falta evidencia que permita realizar la recomendación sobre el tratamiento preventivo.

Metformin is the most widely used oral antidiabetic agent for the treatment of type 2 diabetes (T2D) and the association of the use of this drug with vitamin B12 deficiency has been described. A review of studies was carried out to find out the evidence of this association and the recommendations for its detection, prevention and treatment. The reported prevalence of vitamin B12 deficiency in patients treated with metformin ranged from 5.8% to 52% in the different series. Older patients, those who received metformin at high doses and for a longer time, and those who do not consume food of animal origin, are those who are at greater risk of suffering from this deficit. The determination of vitamin B12 every 1 year is recommended in patients with T2D treated with metformin, and the eventual replacement in case of deficiency. Although there is consensus on the treatment of the deficit, there is still a lack of evidence to make recommendations on a preventive treatment

Déficit de vitamina B12 en grupos vulnerables con alimentación omnívora / Vitamin B12 deficiency in vulnerable groups with omnivorous diet

Introducción: la vitamina B12 cumple un rol esencial en el crecimiento y el neurodesarrollo. El déficit de vitamina B12 (B12) es un problema de salud pública en Argentina, con una alta prevalencia en población de riesgo, como las embarazas y niños en situación social vulnerable, aunque mantengan una dieta omnívora. Objetivos: actualizar la información disponible sobre la deficiencia de B12 en la población vulnerable con el fin de resaltar y actualizar la importancia del tema para realizar un diagnóstico temprano, un tratamiento oportuno y prevenir las complicaciones irreversibles. Resultados: es importante que el pediatra conozca las diferentes formas de presentación del déficit de B12 y principalmente que se considere como diagnóstico diferencial ante niños con alteraciones neurológicas, aún en ausencia de anemia, para lograr intervenciones tempranas que disminuyan el impacto de la enfermedad. Varios investigadores concluyeron que un marcador aislado puede conducir a diagnósticos erróneos, por lo cual actualmente lo más recomendado es usar al menos dos. De los tratamientos evaluados, la mayoría acuerda en realizar entre siete a 10 días de tratamiento, con 1 mg de B12, ya sea intramuscular o vía oral, seguido de tres a 11 semanas de tratamiento semanal. Conclusiones: es de vital importancia relevar datos actualizados de prevalencia de déficit en el país, como así también implementar intervenciones terapéuticas y de políticas públicas preventivas

Introduction: vitamin B12 plays an essential role in growth and neurodevelopment. Vitamin B12 deficiency is a public health problem in Argentina, with a high prevalence in a highrisk population, such as pregnant women and children with a vulnerable social situation, although their omnivorous diet. Objectives: to update the information available on vitamin B12 deficiency in vulnerable populations, in order to highlight the importance of the subject, to achieve an early diagnosis and timely treatment and thus prevent irreversible complications. Results: it is important that the pediatrician knows the different types of vitamin B12 deficiency presentation and to consider it as a differential diagnosis in children with neurological symptoms, even in the absence of anemia, to achieve early interventions and diminish the burden of disease. Many researchers have concluded that an isolated marker can lead to misdiagnoses, so it is currently recommended to use at least two. Most of the treatments evaluated, agree on the administration of 1 mg of B12, for 7 to 10 days, either intramuscular or orally, followed by 3 to 11 weeks of a weekly dose. Conclusions: it is important to update data on the prevalence of B12 deficiency in our country, as well as the implementation of therapeutic interventions and preventive public policies

Pseudomicroangiopatía trombótica por deficiencia de vitamina B12 en un lactante / Pseudo-thrombotic microangiopathy due to vitamin B12 deficiency in an infant

La seudomicroangiopatía trombótica o síndrome de Moschcowitz es una manifestación infrecuente del déficit de vitamina B12. Se caracteriza por anemia hemolítica con características microangiopáticas, reticulocitos e índices hematimétricos normales o con ligera megaloblastosis, asociados a manifestaciones neurológicas. La vitamina B12 está presente en alimentos proteicos de origen animal. La lactancia materna es una fuente adecuada para los niños cuando los niveles maternos son normales. Se presenta a una paciente de 16 meses que se internó por anemia hemolítica con requerimiento transfusional, plaquetopenia, mal progreso pondoestatural y retraso neuromadurativo. Durante su internación se arribó al diagnóstico de seudomicroangiopatía trombótica secundaria a déficit de vitamina B12.

Pseudo-thrombotic microangiopathy, or Moschcowitz syndrome, is a rare manifestation of vitamin B12 deficiency. It is characterized by microangiopathic hemolytic anemia, reticulocytes, and hematimetric indices that can be normal or that might present a mild megaloblastosis, and which are associated with neurological manifestations. Vitamin B12 can be found in animal-based protein foods. Breastfeeding is an adequate source of this vitamin for children, when maternal serum levels are normal. The case of a 16-month-old infant is presented. She was admitted for hemolytic anemia with transfusion requirement, thrombocytopenia, failure to thrive and developmental delay. During her hospitalization, she was diagnosed with pseudothrombotic microangiopathy caused by vitamin B12 deficiency.

Clinical and radiological features of main dementias / Aspectos clínicos e radiológicos das principais demências

Dementia is a syndrome characterized by a decline of two or more cognitive functions, affecting social or professional life. Alzheimer's Disease is a neurodegenerative disorder that represents 53% of dementia cases; memory loss, inability to recognize faces, impaired judgement, disorientation and confusion are possible common symptoms. Vascular Dementia is responsible for 42% of dementia cases, due to cerebrovascular pathologies, and the clinical aspects are related to the extension and location of the brain injury. Lewy Bodies Dementia is a neurodegenerative disorder that represents 15% of dementia cases, and its symptoms include visual hallucinations, parkinsonism and fluctuating cognitive decline. Frontotemporal dementia is a group of clinical syndromes, divided in Behavioral-variant, characterized by disinhibition, compulsions, apathy, aberrant sexual behavior and executive dysfunction; and Primary Progressive Aphasia, which is subdivided in Nonfluentvariant and Semantic-variant. Vitamin B12 deficiency is a reversible cause of dementia, with a wide clinical feature, that includes psychiatric symptoms such as depression and irritability, hematological symptoms related to anemia (e.g. dyspnea and fatigue), and neurological symptoms including dementia and neuropathy. Normal pressure hydrocephalus is also reversible, presenting forgetfulness, changes in mood, decline of executive functions, reduced attention, and a lack of interest in daily activities as symptoms. The radiological findings vary depending on the etiology of dementia. For that reason, understanding neuroimaging and clinical aspects is important to diagnose effectively.

A demência é uma síndrome que consiste em um declínio de um ou mais domínios cognitivos, que afeta o desempenho social ou profissional do indivíduo. A Doença de Alzheimer é um transtorno neurocognitivo que representa 53% dos casos de demência; seus sintomas podem incluir perda de memória, incapacidade de reconhecer rostos familiares, julgamento comprometido desorientação e confusão mental. A Demência Vascular é responsável por 42% dos casos de demência e é causada por doenças cerebrovasculares, seus achados clínicos são relacionados com o local e com a extensão do dano cerebral. Já a Demência por Corpos de Lewy é uma doença neurocognitiva que representa 15% dos casos de demência, cujos sintomas incluem alucinações visuais, parkinsonismo e flutuação cognitiva. A Demência Frontotemporal, por sua vez, é um grupo de síndromes, que se dividem em variante comportamental ­ caracterizada por desinibição, compulsão, apatia, hipersexualidade e disfunções executivas ­ e Afasia Progressiva Primária, subdividida em variante não-fluente e variante semântica, que cursam com disfunções da linguagem. Há, ainda, a Deficiência de Vitamina B12, uma causa reversível de demência. Ela possui um quadro clínico variado, que inclui sintomas psiquiátricos, como depressão e irritabilidade, sintomas hematológicos relacionados a anemia, como dispneia e fadiga) e sintomas neurológicos, que incluem demência e neuropatias. Uma outra causa reversível é a Hidrocefalia de Pressão Normal, que se apresenta com esquecimentos, alterações de humor, perda de função executiva e redução da atenção e do interesse nas atividades cotidianas. Os achados de neuroimagem variam dependendo da etiologia da demência. Assim, compreender os aspectos clínicos e radiológicos é importante para um diagnóstico efetivo..

Comparison of sublingual and intramuscular administration of vitamin b12 for the treatment of vitamin b12 deficiency in children

Abstract Background: In most countries, contrary to some disadvantages, such as pain, relatively higher cost, and poor adherence to treatment, intramuscular (IM) route is still the primary treatment method for Vitamin B12 (VB12) deficiency. In recent years, because of these difficulties, new treatment methods are being sought for VB12 deficiency. Objectives: We aimed to compare sublingual (SL) and IM routes of VB12 administration in children with VB12 deficiency and to compare the efficacy of methylcobalamin and cyanocobalamin therapy in these children. Methods: This retrospective study comprised 129 patients with VB12 deficiency (serum Vitamin 12 level ≤ 200 pg/mL) aged 5-18 years. Based on the formulations of Vitamin 12, we divided the patients into three treatment groups as IM cyanocobalamin, SL cyanocobalamin, and SL methylcobalamin. Results: After Vitamin 12 therapy, serum Vitamin 12 levels increased significantly in all patients, and there was a statistically significant difference between the treatment groups (p < 0.05). Conclusions: SL cyanocobalamin and methylcobalamin were found as effective as IM cyanocobalamin for children with Vitamin 12 deficiency in correcting serum Vitamin 12 level and hematologic abnormalities.

Compromiso neurológico por déficit de vitamina B12 en un lactante / Neurologic involvement due to vitamin B12 deficiency in an infant

El déficit de vitamina B12 es una de las complicaciones más importantes que puede producir el vegetarianismo. Los lactantes hijos de madres vegetarianas tienen riesgo aumentado de deficiencia y de presentar compromiso neurológico irreversible si esta no se identifica y corrige adecuadamente.Se describe el caso de un lactante de un mes y veinte días que consultó por episodios paroxísticos de mecanismo epileptógeno, en el cual los estudios complementarios permitieron identificar un déficit de vitamina B12 como causa de estos. Tras la confirmación diagnóstica, se instauró el tratamiento con vitamina B12 intramuscular, con remisión completa de los síntomas, buena evolución posterior y desarrollo psicomotor sin alteraciones.Teniendo en cuenta las tendencias alimentarias actuales, es necesario incorporar, en la práctica clínica habitual, la anamnesis nutricional materna detallada para detectar precozmente el riesgo de déficit de esta vitamina y prevenirlo

Vitamin B12 deficiency is one of the main complications of vegetarianism. Infants of vegetarian mothers have greater risk of deficiency and irreversible neurological compromise if deficiency is not identified and treated. We describe the case of a 1 month 20 days-old infant who consulted due to paroxysmal episodes of epileptogenic mechanism; laboratory tests identified a deficiency in vitamin B12 as the cause. After confirmation of diagnosis, treatment with intramuscular vitamin B12 was established with full remission of symptoms, good evolution and psychomotor development without alterations.Considering current alimentary trends, it is necessary to include a detailed maternal nutritional anamnesis in regular clinical practice, in order to detect the risk of this vitamin deficiency at an early stage and to prevent it.

Dietas vegetarianas en alumnos universitarios / Vegetarian diets in first year university students

INTRODUCCIÓN: Se ha observado un aumento en la popularidad de las dietas vegetarianas, en especial en la población adolescente y adulto joven. Estas dietas se presentan como saludables y balanceadas pero las recomendaciones son controversiales en cuanto a los potenciales déficit nutricionales. OBJETIVO: Identificar la frecuencia y tipos de dieta vegetariana utilizada, su motivación y fuentes de información. PACIENTES Y MÉTODO: Estudio transversal y analítico en universitarios de primer año de la Pontificia Universidad Católica de Chile (PUC). Se realizó una encuesta vía online obteniendo información demográfica y caracterización de dietas de aquellos que se consideraban vegetarianos. Las variables fueron analizadas mediante el software IDM SPSS Statistics® y en planilla Excel® de forma cuantitativa. RESULTADOS: 152 alumnos respondieron la encuesta (15,2% del total), siendo el 49,4% de estos vegetariano. El 32,4% inició este patrón alimentario entre los 12-18 años; sus motivaciones más frecuentes fueron las medio ambientalistas (91,9%) y animalistas (72,9%). El 52,9% de los vegetarianos reciben suplementación de vitamina b 12 pero solo un 15,9% reportó presentar este déficit. El 75,7% obtiene información relacionada acerca de las dietas vegetarianas a través de medios digitales. CONCLUSIÓN: Se encontró un alto porcentaje de estudiantes vegetarianos en las encuestas contestadas, lo que hace necesario que los profesionales de salud estén capacitados en esta área para asegurar una adecuada educación nutricional, suplementación si es necesario, y seguimiento.

INTRODUCTION: There has been an increase in the popularity of vegetarian diets, especially among adolescents and young adults. These diets seem to be healthy and balanced, but the recommendations are contro versial regarding potential nutritional deficits. OBJECTIVE: To identify the frequency and types of ve getarian diet used, their motivation, and sources of information. PATIENTS AND METHOD: Cross-sec tional analytical study in freshmen students from the Pontifical Catholic University of Chile (PUC). Through an online survey, we collected demographic information and diet characterization of those who considered themselves as vegetarians. Variables were analyzed using IDM SPSS Statistics® soft ware and in Excel® spreadsheet in a quantitative way. RESULTS: 152 students answered the survey (15.2% of the sample) and, out of these, 49.4% were vegetarian. 32.4% started this eating pattern bet ween the ages 12 and 18 and among their most frequent motivations were environmentalists (91.9%) and animalists (72.9%). 52.9% of vegetarians take vitamin B 12 supplementation but only 15.9% reported having this deficiency. 75.7% obtain information related to vegetarian diets through digital media. CONCLUSION: In the surveys answered, we found a high percentage of vegetarian students, the refore, health professionals need to be trained in this area to assure adequate nutritional education, supplementation if necessary, and follow-up.

Serum iron and vitamin B 12 deficiency could indicate celiac disease by flexible spectral imaging color enhancement

SUMMARY INTRODUCTION Celiac disease (CeD) is an autoimmune disease that can be delayed in diagnosis due to the presence of atypical and asymptomatic cases in adulthood. Herein we aimed to study the frequency of CeD and evaluate whether magnified endoscopy and magnified/FICE (flexible spectral imaging color enhancement) techniques contribute to the diagnosis in patients with serum iron and vitamin B12 deficiency. METHODS We evaluated 50 adult patients (10 males and 40 females) who had serum iron and vitamin B12 deficiency, prospectively. All the patients had undergone upper gastrointestinal system endoscopy by the same endoscopist. The second part of the duodenum was evaluated with white light, magnified, and magnified/FICE endoscopy. Biopsy specimens were evaluated by the same pathologist. The specimens diagnosed as CeD were classified according to the Modified Marsh-Oberhuber criteria. RESULTS 10 of 50 patients (20%) were diagnosed as CeD. The average age was 41±11 years (20-67 years). Thirty percent of CeD diagnosed patients had typical CeD symptoms. Six of 10 patients (60%) who were diagnosed as CeD had typical endoscopic images under white lighted endoscopy. All of these 10 patients (100%) showed villous irregularity, partial villous atrophy, or total villous atrophy consistent with CeD with magnified and magnified/FICE endoscopy. CONCLUSION The practical use of magnified/FICE endoscopy allows us to differentiate mucosal abnormalities of the duodenum and minimize false-negative results that indicate normal mucosal findings with conventional endoscopy.

RESUMO INTRODUÇÃO A doença celíaca (DC) é uma doença autoimune que pode ter seu diagnóstico atrasado devido à presença de casos atípicos e assintomáticos na idade adulta. Neste trabalho, objetivamos estudar a frequência de DC e avaliar se as técnicas de endoscopia magnificada e magnificada/Fice (flexible spectral imaging color enhancement) contribuem para o diagnóstico em pacientes com deficiência sérica de ferro e vitamina B12. MÉTODO Foram avaliados prospectivamente 50 pacientes adultos (10 homens e 40 mulheres) com deficiência sérica de ferro e vitamina B12. Todos os pacientes foram submetidos a endoscopia digestiva alta pelo mesmo endoscopista. A segunda parte do duodeno foi avaliada com endoscopia com luz branca, magnificada e magnificada/Fice. As amostras de biópsia foram avaliadas pelo mesmo patologista. Os espécimes diagnosticados como DC foram classificados de acordo com os critérios de Marsh-Oberhuber modificado. RESULTADOS Dez dos 50 pacientes (% 20) foram diagnosticados como DC. A idade média foi de 41±11 anos (20-67 anos). Trinta por cento dos pacientes diagnosticados com DC apresentaram sintomas típicos de DC. Seis dos dez pacientes (60%) diagnosticados com DC tinham imagens endoscópicas típicas sob endoscopia de luz branca. Todos esses dez pacientes (% 100) apresentaram irregularidade das vilosidades, atrofia das vilosidades parciais ou atrofia das vilosidades totais consistentes com a DC com endoscopia magnificada e magnificada/Fice. CONCLUSÃO O uso prático da endoscopia magnificada/Fice permite diferenciar anormalidades mucosas do duodeno e minimizar os resultados falso-negativos que apresentam achados mucosais normais com a endoscopia convencional.

Higher incidence of metabolic syndrome components in vitiligo patients: a prospective cross-sectional study

Abstract Background/Objectives: To investigate the association between vitiligo and metabolic syndrome. Methods: A prospective cross-sectional study was conducted between 2014 and 2016. Study (n = 155) and control groups (n = 155) were evaluated for metabolic syndrome according to National Cholesterol Education Program Adult Treatment Panel III and the International Diabetes Federation criteria. Study group was divided into three groups according to their vitiligo area severity index and vitiligo disease activity score values (Group 1: 6.89 for VASI score, Group A: −1-0, Group B: 1-2 and Group C: 3-4 for vitiligo disease activity score respectively). MetS rates according to both criteria were compared between the vitiligo disease activity score and vitiligo area severity index groups. Results: Metabolic syndrome rates were 37.4% and 40% in the study group and 19.4% and 26.5% in the control group according to National CholesterolEducation Program Adult Treatment Panel III and International Diabetes Federation criteria, respectively (p < 001 and p = 0.011). Metabolic syndrome was more frequent in vitiligo area severity index Groups 2 and 3 compared to vitiligo area severity index Group 1, and in vitiligo disease activity score Group C compared to vitiligo disease activity score Groups A and B. Study limitations: Single center experience, absence of more specific oxidative-stress markers and lack of long-term follow-up of the patients. Conclusions: Frequency of metabolic syndrome was higher in patients with non-segmental vitiligo and the rate was higher in active/severe form of the disease.

Serum vitamin B12 associated with vitamin D/25(OH)D in women with recurrent aphthous stomatitis / Vitamina B12 sérica asociada con vitamina D / 25 (OH) D en mujeres con estomatitis aftosa recurrente

Vitamin B12 and Vitamin D deficiency may contribute to recurrent aphthous stomatitis (RAS). Current studies have showed vitamin B12 to be associated with vitamin D in women, however no study has assessed vitamin B12 associated with vitamin D/25(OH)D in women with RAS. Objective: To investigate the association between serum vitamin B12 and vitamin D/25(OH)D in women with RAS. Materials and Methods: Fourty one women with RAS who meet the inclusion criteria participated in this study. The inclusion criteria were women with RAS without other oral diseases. The exclusions criteria were those who have systemic diseases, taking medications or smoked. All subjects underwent venupuncture to draw blood to quantify serum vitamin B12 and vitamin D/25(OH)D. The characteristic of subjects, severity of RAS, serum Vitamin B12 and Vitamin D/25(OH)D were collected and presented descriptively. The correlation between vitamin B12 and Vitamin D/25(OH)D was analyzed using Pearson correlation test with 95% confidence interval. This study was approved by Medical and Health Ethics Committe, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia. Results: All RAS subjects have normal mean value of serum Vitamin B12 (453.97+154.44pg/ml) and have low mean value of serum vitamin D/25(OH)D (10.79 +3.29ng/ml) categorized as vitamin D deficiency. The Pearson correlation test showed that there was a significant positive correlation between mean serum Vitamin B12 and Vitamin D/25(OH)D (r= 0.313, p<0.05). Conclusion: There is correlation between vitamin B12 and Vitamin D, and a low level of Vitamin D may contribute in RAS in women.

Antecedentes: la deficiencia de vitamina B12 y vitamina D puede contribuir a la estomatitis aftosa recurrente (EAR). Los estudios actuales han demostrado que la vitamina B12 está asociada con la vitamina D en mujeres, sin embargo, ningún estudio ha evaluado la vitamina B12 asociada con la vitamina D/25 (OH) D en mujeres con EAR. Objetivo: investigar la asociación entre la vitamina B12 y la vitamina D / 25 (OH) D sérica en mujeres con RAS. Material y Métodos: Cuarenta y una mujeres con RAS que cumplen con los criterios de inclusión participaron en este estudio. Los criterios de inclusión fueron mujeres con RAS y sin otras enfermedades orales. Los criterios de exclusión fueron aquellos que tenían enfermedades sistémicas, tomaban medicamentos o fumaban. Todos los sujetos se sometieron a una venupuntura para extraer sangre para cuantificar la vitamina B12 y la vitamina D/25 (OH) D en suero. Las características de los sujetos, la severidad del EAR, la concentración de vitamina B12 y la vitamina D/25 (OH) D sérica fueron recolectadas y presentadas descriptivamente. La correlación entre la vitamina B12 y la vitamina D/25 (OH) D se analizó mediante la prueba de correlación de Pearson con un intervalo de confianza del 95%. Este estudio fue aprobado por el Comité de Ética Médica y de Salud, Facultad de Medicina, Universitas Gadjah Mada, Yogyakarta, Indonesia. Resultado: Todos los sujetos con EAR tienen un valor medio normal de vitamina B12 sérica (453,97pg/ml + 154,44pg/ml) y un valor medio bajo de vitamina D sérica/25 (OH) D (10,79 ng/ml + 3,29ng/ml) clasificado como deficiencia de vitamina D. La prueba de correlación de Pearson mostró que había una correlación positiva significativa entre la vitamina B12 media y la vitamina D/25 (OH) D en suero r=0.313, p<0.05). Conclusión: Existe una correlación entre la vitamina B12 y la vitamina D, y un bajo nivel de vitamina D puede contribuir al RAS en las mujeres.

Hiperpigmentación cutánea secundaria a déficit de vitamina B12 en un lactante / Cutaneous hyperpigmentation secondary to vitamin B12 deficiency in an infant

La hiperpigmentación cutánea es una manifestación clínica poco frecuente del déficit de vitamina B12 (cobalamina). Su causa no se conoce con exactitud, y existen varias teorías en su etiopatogenia.Se presenta a una niña de 8 meses de edad, con antecedentes de retraso neuromadurativo, hipotonía, anemia y neutrope-nia, derivada a nuestro Servicio por hiperpigmentación cutá-nea del dorso de las manos y los pies de 3 meses de evolución. Ante la sospecha clínica de déficit de vitamina B12, se realizó un análisis de laboratorio, en el que se constató una marcada disminución de los niveles séricos de cobalamina, por lo que se indicó tratamiento sustitutivo con esta.Se destaca la importancia de la presunción diagnóstica de déficit de vitamina B12 como causa de hiperpigmentación cutánea y su resolución luego de la instauración del tratamiento adecuado.

Cutaneous hyperpigmentation is a rare clinical feature of vi-tamin B12 (cobalamin) deficiency. The cause is unknown and there are different hypothesis about the pathogenesis of the hyperpigmentation.We report the case of an 8-month-old girl, with history of neu-romadurative delay, hypotonia, anemia and neutropenia, who was referred to our Service by brownishhyperpigmentation on her hands and feet of 3 months of evolution. Based on the clinical suspicion of vitamin B12 deficiency, we performed a laboratory dosage that showed decreased levels of cobalamin, reason for which replacement therapy was indicated.It highlights the importance of the presumption of vitamin B12 deficiency as a cause of cutaneous hyperpigmentation and its rapid resolution after the establishment of the appro-priate treatment.

Asociación entre niveles de vitamina B-12 y mortalidad en pacientes hospitalizados adultos mayores / Association between high vitamin B12 levels and one year mortality in older people admitted to the hospital

Background: Supplementation of vitamin B12 in older adults is a common practice to avoid vitamin B12 insufficiency. However, there is a paucity of information about the effects of cobalamin excess. Aim: To asses any potential effects of high levels vitamin B12 on mortality on adults aged ≥ 65 years admitted to an internal medicine service. Material and Methods: We Prospectively studied patients admitted to an internal medicine service of an academic hospital from September 2017 to September 2018, who were able to give their consent and answer questionnaires. We tabulated age, gender, medical history, comorbidity index (Charlson), frailty score (Fried scale), admission diagnosis and blood tests performed within 48 hours of admission. The primary outcome was death by any cause in less of 30 days or after one of year follow up, determined according to death certificates. Results: We included 93 patients aged 65 to 94 years (53% males). Fifteen patients died during the year of follow up (five within 30 days of admission). Those who died had higher cobalamin levels than survivors (1080.07 ± 788.09 and 656.68 ± 497.33 pg/mL respectively, p = 0.02). Patients who died had also a significantly lower corrected serum calcium, sodium (p = 0.04) and a medical history of chronic liver disease (p = 0.03). In the multivariable analysis, only vitamin B12 preserved the association with mortality (p = 0.009). Conclusions: There was a significant association between high levels of cobalamin and all-cause mortality in this group of patients aged ≥ 65 years-old.

Vitamin B12 deficiency in newly weaned goat kids associated with clinical infection with Eimeria arloingi / Deficiência de vitamina B12 em cabritos recém-desmamados associada à infecção clínica por Eimeria arloingi

Abstract A severe outbreak of diarrhea associated with poor growth was reported in ten newly weaned goat kids that originated from a research farm (Group A). Two of these kids underwent necropsy examination. Five goat kids of the same age maintained in the same pen showed no clinical signs (Group B). The clinical, gross pathological and histopathological features of the clinically sick animals were consistent with severe coccidiosis. Group A animals had significantly lower levels of serum vitamin B12 (<200 pg/ml) compared with group B animals (2000 pg/ml). In addition, kids belonging to group A had significantly higher Eimeria arloingi oocysts per gram (OPG) of faeces (101,400/g) compared with kids of group B (9,154/g). Microscopy and molecular tools (18S rRNA and COI genes) confirmed that the goat kids were infected with the caprine protozoan parasite E. arloingi. This study provides a definitive association between low levels of serum vitamin B12 and clinical E. arloingi infection, and also provides support to our previous studies that demonstrated how low levels of serum vitamin B12 leads to an impairment of neutrophil function and thereby potential lowered immunity to pathogens.

Resumo Um surto grave de diarreia, associado à baixo crescimento, foi relatado em dez cabritos recém-desmamados, originários de uma fazenda de pesquisa (Grupo A). Dois animais foram submetidos a exame necroscópico. Cinco cabritos da mesma idade e mantidos na mesma instalação não apresentaram sinais clínicos (Grupo B). As características clínicas e as lesões macroscópicas e microscópicas dos animais clinicamente doentes eram consistentes com coccidiose grave. Os animais do grupo A apresentaram níveis significativamente mais baixos de vitamina B12 sérica (<200 pg / ml) em comparação com os animais do grupo B (2000 pg/ml). Além disso, os animais pertencentes ao grupo A apresentaram um número de oocistos de Eimeria arloingi por grama (OPG) de fezes (101,400/g) significativamente mais alto do que os animais do grupo B (9,154/g). As análises microscópica e molecular (genes 18S rRNA e COI) confirmaram que os cabritos estavam infectados com o protozoário E. arloingi. Este estudo fornece uma associação definitiva entre baixos níveis de vitamina B12 no soro e infecção clínica por E. arloingi. Também fornece suporte aos estudos anteriores, que demonstraram como baixos níveis de vitamina B12 no soro comprometem a função dos neutrófilos e, consequentemente, a imunidade a patógenos.

Deficiencia de cobalamina C de inicio temprano: presentación de caso clínico / Early onset cobalamin C deficiency: clinical case presentation

Cobalamin C (CblC) deficiency is an autosomal recessive disorder caused by mutations of the MMACHC gene that results in impaired synthesis of the methylcobalamin and adenosylcobalamin co-factors. This brings an impaired conversion of dietary cobalamin and therefore dysfunction of two key enzymes generating hyperhomocysteinemia, hypometionimemia and methylmalonic aciduria. It is the most common intracellular metabolism disorder of cobalamin. The early clinical form is the most frequent disorder and appears as a multisystemic disease with developmental delay, failure to thrive, and ocular, renal and hematological involvement during the first year of life. The thromboembolic events are associated with small vessel involvement, generating thrombotic microangiopathy responsible for renal involvement and pulmonary thromboembolism. The late-onset form is characterized by leukoencephalopathy, psychiatric disorders, subacute degeneration of the spinal cord, and thromboembolic events of medium to large vessels. The treatment currently available increases the survival of the patient and improves growth, neurological manifestations, biochemical, hematological profile and hydrocephalus. We present the neonatal debut of a case of CblC deficiency that appeared as a multisystem disease with initial neurological, ocular and hematological manifestations. The onset of symptoms was acute, a characteristic that is not frequent in CblC. The patient started treatment early, but in an unsatisfactory fashion, which led to increased neurological deterioration. Due to MRI images performed during the evolution of his condition, a superior and transverse sagittal sinus thrombosis, a rare manifestation of the disease, was observed.

La deficiencia de cobalamina C (CblC) es un defecto autosómico recesivo causado por la mutación del gen MMACHC, que resulta en la síntesis alterada de los cofactores metilcobalamina y adenosilcobalamina. Esto trae aparejado una disfunción de dos enzimas claves, lo cual genera hiperhomocisteinemia, hipometionimemia y aciduria metilmalónica. La presentación clínica de la deficiencia de CblC es heterogénea, y varía desde las formas de inicio temprano graves y potencialmente mortales, hasta los fenotipos más leves de inicio tardío. La forma clínica temprana es la más frecuente y se manifiesta como una enfermedad multisistémica, con restricción del desarrollo, restricción del crecimiento y alteraciones oculares, renales y hematológicas durante el primer año de vida. Las manifestaciones tromboembólicas están asociadas con el compromiso de pequeños vasos, lo que causa microangiopatía trombótica, responsable de compromiso renal y de tromboembolismo pulmonar. La forma tardía se caracteriza por leucoencefalopatía, trastornos psiquiátricos, degeneración subaguda de la médula espinal y eventos tromboembólicos de medianos o grandes vasos. El tratamiento disponible actualmente aumenta la supervivencia de la enfermedad y mejora el crecimiento, las manifestaciones neurológicas, el perfil bioquímico y hematológico y la hidrocefalia. Presentamos el debut neonatal de un caso de deficiencia de CblC que se manifestó con compromiso inicial neurológico, ocular y hematológico. El comienzo de los síntomas fue agudo, característica que no es frecuente en la deficiencia de CblC. El tratamiento se inició tempranamente, pero en forma insatisfactoria, con evolución de deterioro neurológico. En la evolución de su enfermedad en las imágenes de resonancia magnética, se puso de manifiesto trombosis de los senos sagital superior y transversos, una rara manifestación de la deficiencia de CblC.

Deficiencia de vitamina B 12: una presentación atípica / Vitamin B12 deficiency: an atypical presentation

Resumen La importancia de la detección de la deficiencia de vitamina B12 radica en que es una causa reversible de fallo de medula ósea y desmielinización del sistema nervioso. Se puede presentar en hallazgos de laboratorio con datos de hemólisis con recuento reticulocitario disminuido, a diferencia otras formas de anemia hemolítica. La degeneración combinada subaguda medular es una manifestación atípica de la deficiencia de cobalamina; se trata de un proceso desmielinizante asociado a muerte neuronal, que se manifiesta en individuos con niveles muy bajos de esta vitamina y con síntomas inicialmente neurológicos, como parestesias en extremidades y debilidad generalizada. Se reporta el caso de una paciente femenina de 35 años, con hemólisis asociada a bicitopenia, manejada con altas dosis de esteroides sin mejoría clínica, que luego consultó por cuadro de 2 meses de evolución de parestesias e inestabilidad de la marcha. Al examen físico se documentó marcha atáxica, Romberg positivo y estudios de laboratorio que revelaron anemia megaloblástica con datos de hemolisis y reticulocitos disminuidos.

Abstract Vitamin B12 deficiency it's a reversible cause of bone marrow failure and is associated with demyelination of the nervous system, it's important to make the diagnosis correctly and early to prevent irreversible damage. It can present with laboratory findings suggestive of hemolysis with decreased reticulocyte count unlike other forms of hemolytic anemia. The combined subacute marrow degeneration is an atypical manifestation of cobalamin deficiency, it's a demyelinating process associated with neuronal death that occurs with very low levels of this vitamin, the initial manifestations are neurological symptoms like paresthesia in limbs and generalized weakness. This case report analyzes a 35-year-old female with a recent diagnosis of Evans syndrome, due to the presence of hemolysis. Now she comes with a medical record of 2-month presenting with paresthesias and gait instability. The physical examination documented ataxic gait, positive Romberg sing and laboratory findings that reveal macrocytic anemia and hemolysis data with decreased reticulocytes count.

Estomatitis aftosa recurrente y deficiencias nutricionales: Reporte de tres casos y revisión de literatura / Recurrent Aphthous Stomatitis and Nutritional Deficiencies: Report of Three Cases with Literature Review

RESUMEN Introducción: La estomatitis aftosa recurrente (EAR) es la enfermedad ulcerativa más común que afecta la mucosa oral no queratinizada. La etiología aún se desconoce, pero se han propuesto varios factores locales y sistémicos como agentes causales. Descripción del caso: se informa tres pacientes con presencia de EAR asociada a deficiencias nutricionales, debidas a dietas de restricción alimentaria. El primer caso, una mujer de 19 años con deficiencia de hierro, refirió tomar té verde a diario y consumir poca cantidad de carbohidratos, grasas y carne. El segundo caso, un hombre de 32 años con deficiencia de hierro y vitamina B12 asociada a dieta tipo vegana, aunque a veces si consumía carne. El tercer caso, hombre de 50 años, vegano y exfumador desde hace un año, presentó deficiencia de hierro, vitamina B12 y ácido fólico. En los tres casos un detallado interrogatorio, examen clínico y análisis sanguíneo completo, permitió establecer un adecuado diagnóstico, manejo odontológico y derivación con un nutricionista, con el fin de tratar la patología de base y no sólo brindarles un tratamiento sintomático de las lesiones. Discusión: Ante un cuadro de EAR es recomendable realizar un análisis que incluya hemograma, ácido fólico, hierro y vitamina B12, para descartar posibles causas sistémicas y eventualmente tratarlas. El manejo clínico tiene como objetivo mejorar la función del paciente y la calidad de vida mediante terapias tópicas y sistémicas; sin embargo, es fundamental identificar y controlar los factores causales que contribuyen; así como, la exclusión o tratamiento de la enfermedad sistémica subyacente.

ABSTRACT Introduction: Recurrent aphthous stomatitis (RAS) is the most common ulcerative disease that affects the non-keratinized oral mucosa. The etiology is still unknown, but several local and systemic factors have been proposed as causal agents. Case description: three patients are reported with RAS associated with nutritional deficiencies, due to dietary restriction diets. The first case, a 19-year- old woman with iron deficiency, reported taking green tea daily and consuming a small amount of carbohydrates, fats and meat. The second case, a 32-year-old man with iron deficiency and vitamin B12 associated with vegan diet, although sometimes if he consumed meat. The third case, man of 50 years, vegan and ex-smoker for a year, presented deficiency of iron, vitamin B12 and folic acid. In all three cases a detailed questioning, clinical examination and complete blood analysis allowed to establish an adequate diagnosis, dental management and referral with a nutritionist, in order to treat the underlying pathology and not only provide a symptomatic treatment of the injuries. Discussion: In the setting of RAS, it is advisable to perform an analysis that includes a blood count, folic acid, iron and vitamin B12, to rule out possible systemic causes and eventually treat them. Clinical management aims to improve patient function and quality of life through topical and systemic therapies; however, it is essential to identify and control the causal factors that contribute; as well as, the exclusion or treatment of the underlying systemic disease.