Transcobalamin deficiency - a rare genetic defect in transportation of cobalamin; case report.

BACKGROUND: Vitamin B12 is primarily transported from plasma to cells by Transcobalamin. Deficiency of Transcobalamin is a rare autosomal recessive disorder that results in unavailability of cobalamin in cells and accumulation of homocysteine and methylmalonic acid. CASE REPORT: We report a case of a 2-year-old male child with persistent pancytopenia, recurrent infections, and megaloblastic anemia. Next-generation sequencing identified a novel variant in exon 8 of TCN2 gene. Substantial improvement has been observed following administration of high doses of parenteral methylcobalamin. CONCLUSION: In patients with unresolved pancytopenia and megaloblastic anemia, Transcobalamin deficiency should be investigated and treated promptly to prevent any irreversible and harmful outcome.

[Bibliometric visualization analysis of thiamine-responsive megaloblastic anemia syndrome].

Visual analysis of the current status, research hotspots, evolving trends, and future prospects in the field of thiamine-responsive megaloblastic anemia syndrome (TRMA), providing new insights and directions for subsequent research on the pathogenic mechanisms and prevention strategies of TRMA. Taking the core database of Web of Science as the literature source, selecting TRMA-related literature records published from 1997 to 2023 as the research object, and using R software and Citexs database to conduct visual analysis and discussion of the research content. The results showed that a total of 89 publications related to the topic were published from 1997 to 2023, with an average annual publication volume of 3 papers. Classified by country, it was found that the United States, and Israel among other countries and institutions, published a significant number of papers. Through keyword frequency analysis, high frequencies of keywords such as diabetes, deafness, thiamine-responsive megaloblastic anemia, and mutations in the solute carrier family 19 member 2 (SLC19A2) gene were observed, indicating that to date, these keywords have been the main research directions, highlighting a gradually reached consensus on the mechanism exploration of TRMA. In conclusion, TRMA research focuses on the mechanisms of hot topics such as diabetes, deafness, and thiamine-responsive megaloblastic anemia, and the core gene SLC19A2 research may currently become a new breakthrough point for future molecular studies.

Polycythemia Vera Masked by Megaloblastic Anemia.

Polycythemia vera (PV) is a chronic myeloproliferative disorder characterized by uncontrolled red blood cell production. Megaloblastic anemia is caused by deficiency of cobalamin (vitamin B12) and/or folate (vitamin B9). While B12 deficiency may be caused by insufficient dietary intake or impairment of its utilization, its association with PV is described without exact knowledge of the physiopathology. We herein report the occurrence of megaloblastic anemia due to Vitamin B12 deficiency in an 85-year-old North African woman patient with PV. This case highlights this atypical presentation of PV and challenges that comes with it causing the delay of diagnosis and the complexity of its diagnosis and treatment. Keywords: megaloblastic anemia, polycythemia vera, association, case report.

Severe megaloblastic anemia in a patient with advanced lung adenocarcinoma during treatment with erlotinib: a case report and literature review.

BACKGROUND: Erlotinib is a first-generation, tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR-TKI) used for the treatment patients with NSCLC. Erlotinib is considered as a safe and effective treatment option, with generally good tolerance. Diarrhea and rash are the most common side effects, and more rare side effects appear in long-term real-world applications. Severe erlotinib related megaloblastic anemia is rare and remains unreported. This is the first case report of severe megaloblastic anemia in a patient with advanced lung adenocarcinoma with an EGFR L858R mutation treated with erlotinib. In this report, the clinical manifestations, diagnosis and treatment of erlotinib related severe megaloblastic anemia are described, and the possible pathogenesis and related treatment options are discussed. CASE DESCRIPTION: Herein, we present a 57- year-old non-smoking female diagnosed with metastatic lung adenocarcinoma harboring an EGFR L858R mutation, who had received erlotinib as the first-line therapy. After 44 weeks of treatment, the patient developed severe anemia. Anemia was manifested as megaloblastic anemia with elevated mean corpuscular volume and mean corpuscular hemoglobin. The total vitamin B12 level was below the detection limit of 50.00 pg /mL. Bone marrow smear suggested megaloblastic anemia. Her hematologic parameters were markedly recovered following the withdrawal of erlotinib and vitamin B12 supplement. As a result, the patient was diagnosed with erlotinib-associated megaloblastic anemia. CONCLUSIONS: This is the first case of severe megaloblastic anemia reported with erlotinib. Few of these hematologic adverse effects have been observed in studies on erlotinib, this case report highlights this possibility for long-term erlotinib administration. Close clinical and blood monitoring is recommended for patients receiving long-term TKI therapy.

Vitamin B12 deficiency-induced megaloblastic anemia in a pediatric patient with autism spectrum disorder with a chronically unbalanced diet.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by a lack of behavioral flexibility and stereotyped language. Food selectivity is common among children with ASD because of their persnickety nature. A prolonged unbalanced diet results in an increased risk of several diseases, such as iron deficiency anemia, scurvy, rickets, dry eye, and Wernicke encephalopathy. However, no cases of megaloblastic anemia have been reported to date. We report the case of an 11-year-old boy with ASD who developed megaloblastic anemia due to vitamin B12 deficiency. He had a prolonged history of selective eating for more than 10 years. His nutritional status on admission was poor, and he had low weight and short stature. His food selectivity was so strong that intervention to expand diet variety was unsuccessful. A developmental-behavioral pediatrician found that the patient had visual dominance and could take some medications when suffering from a minor illness. Nutritional supplements were selected after consultation with a nutritionist. Although compulsory treatment was necessary during the acute phase, the therapy was continued at home. With multidisciplinary intervention tailored to the patient and his parents' characteristics, his nutritional status improved in a few months.

Knuckle hyperpigmentation in a young male: A clinical sign of B12 deficiency not to be missed.

Vitamin B12 and folate deficiency are reversible causes of megaloblastic anemia. Strict vegetarians are at risk of megaloblastic anemia due to low cobalamin in their diet. Knuckle hyperpigmentation in patients with megaloblastic anemia is due to excess melanin synthesis in skin. Here we present a case of a young vegetarian male with megaloblastic anemia with knuckle hyperpigmentation managed successfully with intravenous followed by oral vitamin b12 and folate supplementation.

Polimorfismo de proteína 5, 10-metilentetrahidrofolatoreductasa en población venezolana / Polymorphisms proteína 5, 10-metilentetrahidrofolatoreductasa in venezuelan people

El folato es un miembro del grupo de la vitamina B y está relacionado con enfermedades crónicas como anemia megaloblástica, enfermedad cardiovascular, cáncer, disfunción cognitiva y riesgo de defectos del tubo neural. La proteína 5,10-metilentetrahidrofolato reductasa (MTHFR) juega un papel clave en el metabolismo del folato mediante la síntesis de nucleótidos y reacciones de metilación. El gen MTHFR se encuentra en el cromosoma 1 (1p36.3), y se han descrito dos alelos comunes, el alelo C677T (termolábil) y el alelo A1298C.El objetivo de este estudio es evaluar la distribución de los polimorfismos genéticos en MTHFR C677T y A1298C en la población venezolana. METODOS: estudio de tipo transversal, descriptivo, experimental y correlacional Las muestras de sangre se colectaron en 314 donantes no emparentados y sanos de la población. Los polimorfismos de un solo nucleótido(SNP) MTHFR 677C>T y 1298A>C se analizaron mediante polimorfismo de longitud de fragmento de restricción de reacción en cadena de polimerasa (PCR-RFLP). El desequilibrio de ligamiento (LD) entre pares de SNP se calculó mediante la prueba X. usando Prism 5 (GraphPad software, Inc). RESULTADOS: Encontramos mayor frecuencia genotípica de heterocigotos para el polimorfismo MTHFR C677T en la población general venezolana, con excepción del grupo caucásico. El polimorfismo MTHFR A1298C en el 70%de la población de estudio es homocigoto de tipo salvaje, encontrándose una baja frecuencia de homocigoto mutado. CONCLUSIONES: Se encontraron diferencias significativas entre grupos étnicos, destacando la importancia del genotipado racial de estos polimorfismos en la población venezolana(AU)

Folate is a member of the vitamin B and it has also been indicated that may be related to chronic diseases such as megaloblastic anemia, cardiovascular disease, cognitive dysfunction and risk of neural tube. Methylenetetrahydro folatereductase (MTHFR) is a key enzyme of folate pathway by nucleotide synthesis and methylation reactions. Several polymorphisms were reported in MTHFR gene but C677Tand A1298 polymorphism are most studied and these have been reported to be risk factor for several diseases/disorders. The present study was designed to determine the frequency of MTHFR polymorphisms in Venezuelan healthy population. METHODS: The blood samples were collected from 314 unrelated and healthy donors from population. Both the MTHFR 677C>T and 1298A>C single nucleotide polymorphisms (SNPs) were analyzed by Polymerase chainreaction-restriction fragment length polymorphism (PCR-RFLP). Linkage disequilibrium (LD) between pair of SNPs was calculated through the .. test using Prism 5 (GraphPad sftoware, Inc). RESULTS: We find higher genotypic frequency of heterozygotes for the MTHFR C677T polymorphism in the Venezuelan general population, with the exception of the Caucasian group. MTHFR A1298C polymorphism in 70%of the study population is homozygous wild type, finding alow frequency of homozygous mutated. CONCLUSIONS: Significant differences between ethnic groups were found,highlighting the importance of racial genotyping of these polymorphisms in the Venezuelan population(AU)

Thiamine-Responsive Megaloblastic Anaemia With Hypothyroidism, A Puzzling Association.

Background: Thiamine-responsive megaloblastic anaemia (TRMA) is characterized by the classic trio of diabetes mellitus, sensorineural hearing loss, and megaloblastic anaemia, typically emerging subtly between infancy and adolescence. Administration of high-dose thiamine often yields improvements in anaemia and occasionally in diabetes. Uncommon manifestations include optic atrophy, congenital heart defects, short stature, and stroke. In this specific case, a 5-year-old diagnosed with insulin-dependent diabetes mellitus (IDDM) since the age of one presented with symptoms such as polyuria, fever, and vomiting, revealing an HbA1c of 10.64. Further examinations disclosed compromised hearing and vision. A negative antibody workup and a thyroid profile indicating hypothyroidism prompted additional investigations, including Brainstem Evoked Response Audiometry (BERA) and retinal examination, confirming bilateral sensorineural hearing loss and maculopathy, respectively. A comprehensive blood count unveiled megaloblastic anaemia. Genetic profiling confirmed a homozygous mutation in the SLC19A2 gene, thus diagnosing TRMA. An early diagnosis, coupled with genetic confirmation, enables timely intervention, with patients responding positively to high-dose thiamine. Genetic counselling plays a pivotal role in enlightening families about the disease and its inheritance patterns, fostering awareness and understanding.

Thiamine-responsive megaloblastic anaemia.

We report a 26-year-old girl who was diagnosed with diabetes mellitus in her childhood and was treated with insulin. With a history of visual disturbances during her childhood and anaemia, which was partially evaluated; the possibility of syndromic diabetes was considered. Genetic analysis was done and revealed a mutation in the SLC19A2 gene, confirming the diagnosis of thiamine-responsive megaloblastic anaemia. She was supplemented with thiamine, which dramatically improved her haemoglobin levels and glucose control. However, her vision could not be salvaged as the rod-cone dystrophy is a permanent damage.

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)

Anemia y patología digestiva / Anemia and digestive diseases / Anemia e patologia digestiva

Cada vez más los pacientes diagnosticados con anemia son referidos al gastroenterólogo para su evaluación. La necesidad de realizar un adecuado planteo clínico y una correcta interpretación de las pruebas de diagnóstico ha motivado la revisión de este tema. Varios trastornos gastroenterológicos, con frecuencia, conducen a anemia como resultado de pérdidas sanguíneas, inflamación, malabsorción o a consecuencia de las terapias farmacológicas. En algunas patologías como la cirrosis, EII o neoplasias las causas son a menudo multifactoriales. Esta revisión, pretende proporcionar un enfoque útil para la práctica clínica. Para ello se ha revisado la información actualizada acerca de la patogénesis, diagnóstico y tratamiento de la anemia vinculada a patologías digestivas y se han confeccionados cuadros y algoritmos para facilitar su comprensión.

More and more patients diagnosed with anemia are referred to the gastroenterologist for evaluation. The need to carry out an adequate clinical approach and a correct interpretation of diagnostic tests has motivated this review. Several digestive diseases frequently lead to anemia because of blood loss, inflammation, malabsorption, or drug therapies. In some of them such as cirrhosis, IBD or neoplasms, the etiology is multifactorial. This review is intended to provide a useful approach to clinical practice. To this aim, updated information on the pathogenesis, diagnosis, and treatment of anemia related to digestive diseases has been reviewed, and tables and algorithms have been built to favor its understanding.

Cada vez mais pacientes diagnosticados com anemia são encaminhados ao gastroenterologista para avaliação. A necessidade de realizar uma abordagem clínica adequada e uma interpretação correta dos testes de diagnóstico motivou a revisão deste tema. Vários distúrbios gastroenterológicos freqüentemente levam à anemia como resultado de perda de sangue, inflamação, má absorção ou pelas próprias terapias farmacológicas. Em algumas patologias como cirrose, DII ou neoplasias, as causas costumam ser multifatoriais. Esta revisão visa fornecer uma abordagem útil à prática clínica. Para esse fim, foram revisadas informações atualizadas sobre a patogênese, o diagnóstico e o tratamento da anemia associada à patologia digestiva e foram elaboradas tabelas e algoritmos para facilitar seu entendimento.

Deficiência de cianocobalamina como causa de pancitopenia: relato de um caso e levantamento de literatura / Cyanocobalamin deficiency as a cause of pancytopenia: case report and survey of literature

Contexto: A pancitopenia é uma condição clínica grave caracterizada pela diminuição simultânea dos níveis séricos dos glóbulos vermelhos, brancos e plaquetários. A sua resolução só ocorre quando tratado o processo etiológico. Descrição do caso: Nesse estudo, relatou-se o caso de um paciente pediátrico, procedente de região carente, que foi trazido ao serviço de referência da região pela mãe com quadro progressivo de queda do estado geral, inapetência, diarreia, náuseas e vômitos. Esses sintomas haviam se iniciado cinco dias antes. No recordatório alimentar, a responsável relatou dieta pobre em alimentos de origem animal e vegetal, tendo, ainda, histórico de internação recente. Ao exame físico, apresentou-se hipocorado, com palidez cutânea, sinais vitais normais e sem demais alterações dignas de nota. Inicialmente, solicitaram-se exames complementares que mostraram pancitopenia associada a leucocitúria. Instituídos sintomáticos e antibioticoterapia de amplo espectro para determinado foco. No sexto dia de internação, o paciente evoluiu com quadro séptico, necessitando de transferência e terapia intensiva. Após estabilização do quadro infeccioso, o paciente retornou à enfermaria do serviço para continuidade do tratamento e investigação etiológica da pancitopenia. Por meio de exames complementares, foi possível identificar que a anemia normocítica e normocrômica se tratava de deficiência de vitamina B12 de apresentação atípica. Discussão: Diante de casos com apresentação atípica associada à pancitopenia, é necessário considerar a possibilidade de deficiência de micronutrientes, por se tratar de uma condição frequente em nosso país. Conclusão: O presente relato de caso pode ser utilizado como alerta a profissionais de saúde, para que considerem a deficiência de cianocobalamina como causa de pancitopenia, principalmente em regiões mais vulneráveis, visto que essa condição pode estar associada a quadros graves e que ameaçam a vida.

Anemia Megaloblástica, generalidades y su relación con el déficit neurológico / Megaloblastic anemia, generalities and relationship with neurological deficit

Las anemias megaloblásticas agrupan una serie de desórdenes que se caracterizan por el cambio morfológico de los eritrocitos y su alteración en el desarrollo y maduración a nivel de la médula ósea. Las causas de anemia megaloblástica son numerosas, pero en la mayoría de los casos es debido a deficiencia de folatos y vitamina B12. Esta última, se ve involucrada en múltiples procesos fisiológicos y metabólicos incluyendo el desarrollo del sistema nervioso central, la síntesis de neurotransmisores y la integridad celular. El déficit o ausencia de dichos compuestos genera anemia megaloblástica, una condición que deforma las células sanguíneas y causa diversos síntomas tales como fatiga, debilidad, adelgazamiento y en la primera infancia puede generar deficiencias intelectuales y trastornos motores persistentes. Se realizó una búsqueda bibliográfica con el objetivo hacer una revisión de la deficiencia de la vitamina B12 y folatos en relación con sus complicaciones a nivel neurológico..(AU)

Megaloblastic anemias group a series of disorders that are characterized by the morphological change of the erythrocytes and their alteration in the development and maturation at the level of the bone marrow. The causes of megaloblastic anemia are numerous, but in most cases it is due to a deficiency of folates and vitamin B12. This last has been involved in multiple physiological and metabolic processes including the development of the central nervous system, the synthesis of neurotransmitters and cellular integrity. The deficit or absence of these compounds generates megaloblastic anemia, a condition that deforms blood cells and causes various symptoms such as fatigue, weakness, weight loss and in early childhood can generate intellectual deficiencies and persistent motor disorders. A bibliographic search was carried out in order to review the deficiency of vitamin B12 and folate in relation to its complications at the neurological level..(AU)

Anemia severa por déficit de vitamina b 12 asociado a consumo de metformina / Severe anemia caused by vitamin b12 deficiency associated to metformin use

Resumen La Diabetes Mellitus tipo 2 se ha convertido en un problema de salud pública en el mundo por su alta carga de morbimortalidad y costos por las complicaciones a corto y largo plazo. La Metformina es el antidiabético más comúnmente ordenado para el tratamiento por su costoefectividad y seguridad cardiovascular(1). Presentamos un paciente con sincope por anemia severa megaloblástica causada por déficit de Vitamina B 12 donde la única explicación fue consumo crónico de Metformina. Recibió manejo con Cianocobalamina y presentó recuperación de los parámetros eritrocitarios. Es importante llamar la atención en la monitorización periódica de los niveles de vitamina B 12 en esta población, sobretodo en pacientes que se presentan con síntomas de neuropatía periférica o anemia.

Abstract Type 2 Diabetes Mellitus has become a public health concern globally due to its high morbidity, mortality and costs caused by short and long-term complications. Metformin is the antidiabetic drug most frequently prescribed because its cost-effectiveness and cardiovascular safety. We present the case of a patient with syncope caused by a severe megaloblastic anemia associated to Vitamin B12 deficiency, in which the only possible cause found was the chronic use of Metformin. Patient received treatment with Cyanocobalamin and showed improvement in erythrocyte indices. It is relevant to highlight importance of the periodic monitoring of Vitamin B12 levels in this type of patients, especially in those presenting symptoms of peripheral neuropathy or anemia.

Trastornos neurológicos graves en lactante con anemia megaloblástica / Severe neurological disorders in an infant with megaloblastic anemia

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. Se presenta el caso de una lactante, cuya madre tuvo una alimentación precaria durante el embarazo y la lactancia, que prolongó la lactancia materna exclusiva más de 6 meses. La paciente tuvo un desarrollo psicomotor normal hasta los 7 meses cuando comenzó a perder las habilidades ganadas y llegó a tener trastornos neurológicos graves, por lo que se consideró por neurología como una enfermedad progresiva del SNC. Al examen físico se encontró palidez en piel y mucosas, pérdida de los reflejos cocleopalpebrales bilaterales, ausencia de reflejo visual, hipertonía de los 4 miembros e hiperreflexia. Se realizaron exámenes de laboratorio por genética buscando errores congénitos del metabolismo, enfermedades mitocondriales u otras enfermedades como Tay Sachs, gangliosidosis tipo 1 y leucodistrofia metacromática, todas con resultado negativo. Se encontraron valores bajos de hemoglobina, con macrocitosis, por lo que se realizó dosificación de vitamina B12 que se encontró disminuida. Se concluyó como una anemia megaloblástica por déficit de vitamina B12.Se inició tratamiento sustitutivo con vitamina B12, con lo que se logróuna rápida recuperación clínica desde los primeros días de tratamiento y la remisión total de los trastornos neurológicos. El déficit de vitamina B12 debe ser sospechado en lactantes con anemia y trastornos neurológicos especialmente si la alimentación de la madre antes, durante el embarazo y la lactancia no es adecuada(AU)

Megaloblastic anemia is a madurative disorder of erythroid and myeloid precursors caused by deficiency of vitamin B12 and/or folic acid. It is rare in childhood and its prevalence is unknown because it is a rare disease.We report the case of a 14 month old infant with a normal psychomotor development (DPM) until 7 months after which began to lose the gained skills and had severe neurological disorders to such a degree of being studied by neurology by a progressive central nervous system disease. At physical examination pale skin and mucous membranes, loss of bilateral cocleopalpebral reflexes, no visual reflection of the 4 limbs hypertonia, hyperreflexia were found. Laboratory tests were performed reporting hemoglobin of 76 g/L, genetic tests to search for inborn errors of metabolism,mitochondrial diseases and other diseases as Tay Sachs, Gangliosidosis type 1, metachromatic leukodystrophy, all were negative. The dosage of vitamin B12 was 91 pg/mL, and megaloblastic anemia was diagnosed. At the beginning of the treatment with vitamin B12 there was a rapid clinical recovery, the severe neurological disorders were completely reversing. Vitamin B12 deficiency should be suspected in infants with anemia and neurological disorders especially if the mother´s feeding before and during pregnancy and lactation is not adequate(AU)

Síndrome de anemia megaloblástica sensible a la tiamina de aparición en la niñez, con mutación en el genSLC19A2: caso clínico / Infantile-onset thiamine responsive megaloblastic anemia syndrome with SLC19A2 mutation: a case report

Antecedentes. El síndrome de anemia megaloblástica sensible a la tiamina (TRMA, por sus siglas en inglés), también conocido como síndrome de Rogers, se caracteriza por presentar anemia megaloblástica, hipoacusia neurosensorial y diabetes mellitus. Las alteraciones en el transporte de la tiamina hacia las células se deben a mutaciones homocigotas o heterocigotas compuestas en el gen SLC19A2. Presentación de un caso. Presentamos el caso de una niña que manifestaba sordera neurosensorial tratada con una prótesis auditiva, diabetes con necesidad de insulina y anemia macrocítica, tratada con tiamina (100 mg/día). El nivel de hemoglobina mejoró hasta alcanzar 12,1 g/dl después de aumentar la dosis terapéutica de tiamina hasta 200 mg/día. Conclusión. Se debe evaluar a los pacientes con TRMA para detectar anemia megaloblástica, hipoacusia neurosensorial y diabetes mellitus. Se les debe dar seguimiento para determinar la respuesta de la enfermedad hematológica y de la diabetes después de la terapia con tiamina. La dosis terapéutica de tiamina puede aumentarse según la respuesta clínica. Debe proporcionarse asesoramiento genético.

Background. Thiamine-responsive megaloblastic anemia syndrome (TRMA), also known as Rogers syndrome, is characterized by megaloblastic anemia, sensorineural hearing loss, and diabetes mellitus. Disturbances of the thiamine transport into the cells results from homozygous or compound heterozygous mutations in the SLC19A2 gene. Case presentation. We report a girl which presented with sensorineural deafness treated with a hearing prosthesis, insulin requiring diabetes, macrocytic anemia, treated with thiamine (100 mg/day). Hemoglobin level improved to 12.1 g/dl after dose of thiamine therapy increased up to 200 mg/day. Conclusion. Patients with TRMA must be evaluated for megaloblastic anemia, sensorineural hearing loss, and diabetes mellitus. They must be followed for response of hematologic and diabetic after thiamine therapy. It should be kept in mind that dose of thiamine therapy may be increased according to the clinical response. Genetic counseling should be given.

Perfil nutricional e prevalência de anemia em gestantes adolescentes / Nutritional status and prevalence of anemia in pregnant adolescent

Objetivos: Avaliar o perfil nutricional no início do pré-natal e a associação entre anemia e resultados perinatais em gestantes adolescentes. Métodos: Esta dissertação aborda resultados de dois projetos de pesquisa distintos. Projeto 1: Corte transversal. Foram coletados dados sócios-demográficos, hábitos, comorbidades, hemoglobina sérica, tratamento para anemia, intercorrências da gestação, via de parto, e dados do recém-nascido de gestantes adolescente que tiveram pré-natal e parto no CAISM. A amostra foi dividida em: gestantes adolescentes sem anemia, com anemia tratada e com anemia sem tratamento. Frequências, médias, desvios-padrão e teste de Qui-quadrado foram calculados. Projeto 2: Corte transversal prospectivo. Foram coletados dados sociais demográficos, reprodutivos, dietéticos e antropométricos, de primigestas adolescentes, antes da 20a semana de gestação, através de questionário padronizado, Recordatório de 24 horas, Índice de Massa Corpórea (IMC) e percentagem de gordura corporal (%GC) por dobras cutâneas (DC) e análise da composição corporal por impedância bioelétrica (BIA). Utilizou-se teste de Qui-quadrado e teste exato de Fisher para as variáveis contínuas e teste de Correlação de Spearman para análise das variáveis dietéticas segundo variáveis antropométricas. Resultados: No primeiro estudo foram analisadas 458 gestantes, com prevalência de anemia de 41.27%, sendo 27.07% anemia leve, 13.97% anemia moderada e 0.22% anemia severa, destas 87.24% receberam tratamento. A idade média foi 16 anos, 81.03% primigestas. Os subgrupos de análise apresentaram características sociais demográficas, obstétricas e hábitos similares. Síndromes hipertensivas (5.75%), infecções do trato urinário (4.2%) e diabete (2.88%) ocorreram sem diferença entre os grupos. O HIV+ foi mais prevalente entre adolescentes com anemia não tratada (p=0.018). Trabalho de parto prematuro, Capurro<37 e óbito fetal apresentaram associação com anemia não tratada (p=0.003, p=0.036 e p=0.004 respectivamente). Taxa de cesariana de 36.9%, as principais indicações e médias de peso dos recém-nascidos foram similares entre os grupos. No segundo estudo foram incluídas 87 adolescentes com idade média de 15(±1.4) anos. IMC pré-gestacional médio de 22.9Kg/m² (±4.2) sendo, 13.8% baixo peso, 59.8% eutrófica, 18.4% sobrepeso e 8% obesa, e na primeira consulta de pré-natal IMC médio de 22.9 (±4.2), 4.6% baixo peso, 63.2% eutrófica, 20.7% sobrepeso e 11.5% obesas. A variação média de peso foi 1.7Kg(±4,4). A %GC média por DC e BIA foi 31.9% (±4.4) e 28.7% (±4.6), respectivamente, com forte correlação entre os dois métodos (r=0.77372). O consumo energético médio foi 116.8% (±67.2) da recomendação diária média (1805.5Kcal/dia; ±67.2). Consumo de carboidrato foi adequado em 24.1% das gestantes, lipídio em 34.5% e proteína em 72.4%. Cálcio foi consumido inadequadamente em 94.3% e zinco 62.1%, e ferro e ácido fólico ambos em 98.9% das gestantes. O consumo de proteína e zinco tiveram correlação negativa com a %GC por ambos os métodos (r=-0.3096 e r=-0.2363, respectivamente). Conclusões: As adolescentes apresentaram alta prevalência de anemia, que se não tratada aumentou a ocorrência de parto prematuro e óbito fetal. Adolescentes também apresentam IMC médio eutrófico, elevado %GC, baixa ingestão de micronutrientes cálcio, ferro e ácido fólico. A medida das dobras cutâneas e da BIA apresentaram boa correlação na avaliação da %GC. A adesão ao tratamento através de uma assistência de pré-natal multidisciplinar às gestantes adolescentes pode ser a chave para a redução de desfechos neonatais negativos associados a nutrição. (AU)

Objective: Evaluate the nutritional status in early pregnancy and the association between anemia and perinatal outcomes in pregnant adolescents. Methods: This master dissertation addresses results of two different research projects. Project 1: A cross-sectional study. Sociodemographic data, habits, comorbidities, serum hemoglobin, treatment for anemia, pregnancy complications, mode of delivery, and neonatal outcomes were collected. The sample was divided in three groups: pregnant adolescents without anemia, with treated anemia and with untreated anemia. Frequencies, means, standard deviations and Chi square test were calculated. Project 2: A prospective cross-sectional study. Sociodemographic, reproduction, dietetics and anthropometric data were collected from primiparous adolescents, before the 20th week of pregnancy, by standardized questionnaire, 24 hours recall, body mass index (BMI) and body fat percentage (%BF) by subcutaneous adiposity (SA) and body composition by bioelectrical impedance analysis (BIA). For continues variables Qui-square test and Fisher test were used and Spearman's Rank-Order Correlation test for dietetics variables analyses according to anthropometric variable. Results: In the first study were included 458 pregnant adolescents, with prevalence anemia of 41.27%. Mild, moderate or severe anemia was presented in 65.60%, 33.86% and 0.52%, respectively. The mean age was 16 years, 81.03% primiparous. Among pregnant adolescents with anemia, 87.24% received treatment with iron supplementation. The three groups show similar demographic social characteristics, obstetric and habits. Hypertensive syndromes (5.75%), urinary tract infection (4.2%) and diabetics (2.88%), were the most frequency maternal comorbidity, with no difference among the groups. Positive HIV was more prevalent in adolescents with non-treated anemia (p=0.018). Preterm labor (p=0.003), gestational birth age at <37 weeks (p=0.036) and stillbirth (p=0.004) shown association with non-treated anemia. The caesarean rate was 36.90%, and its main indications and mean weight of newborn were similar between groups. In the second study were included 87 adolescents with an average age of 15(±1.4) years. The pre-gestational BMI mean was of 22.9Kg/m² (±4.2), while other values were 13.8% low weight, 59.8% eutrophic, 18.4% overweight and 8% obese. At the first prenatal visit the values were 22.9(±4.2), 4.6% low weight, 63.2% eutrophic, 20.7% over eight and 11.5% obese. The mean weight variation was 1.7Kg (±4,4). The mean of %BF by SA and BIA were 31.9% (±4.4) and 28.7% (±4.6), respectively, with strong correlation in both methods (r=0.77372). The average energy consumption was 116.8% (±67.2) of the average daily recommendation (1805.5Kcal/dia; ±67.2). Carbohydrate was suitable in 24.1% of adolescents, lipid 34.5% and protein 72.4%. Calcium was inappropriately consumed in 94.3%, zinc in 62.1% and iron and folic acid, both in 98.9% of adolescents. Protein and zinc consumption had negative correlation with the %BF, by both methods (r=-0.3096 e r=-0.2363). Conclusion: High prevalence of anemia, which if left untreated increase the prevalence of preterm birth and stillbirth. The pregnant adolescents presented a eutrophic BMI, with high %BF, low consumption of calcium, iron and folic acid. The measure SA and BIA showed good correlation in the evaluation of %BF. Adherence to treatment by a multidisciplinary prenatal care for pregnant adolescents may be the key to reducing adverse neonatal outcomes associated with food.(AU)

Deficiência de vitamina B12 e fenilcetonúria / Vitamin B 12 deficiency and phenylketonuria

A fenilcetonúria, doença metabólica hereditária, autossômica recessiva, é a mais frequente das aminoacidopatias. Quando não diagnosticada e tratada precocemente, causa retardo mental grave. Os programas de triagem neonatal transformaram a histó- ria natural dessa doença, possibilitando o diagnóstico neonatal e a instituição imediata do tratamento dietético. Atualmente, os pacientes com controle adequado têm vida normal. Nas últimas décadas, alterações nutricionais têm sido relacionadas ao tratamento dietético e aos seus desvios, especialmente após a primeira década de vida. Neste artigo apresenta-se o caso de um adolescente que desenvolveu anemia megaloblástica por deficiente ingestão de vitamina B12 e uma revisão da literatura sobre o tema.(AU)

Phenylketonuria, inherited metabolic disease, autosomal recessive, is the most common of aminoacidopathies. If not diagnosed and treated early, causes severe mental retardation. The newborn screening programs have transformed the natural history of this disease, allowing the neonatal diagnosis and the immediate institution of dietary treatment. Currently, patients with adequate control have normal life. In recent decades, nutritional changes have been related to dietary treatment and its deviations, especially after the first decade of life. In this article we present the case of a teenager who developed megaloblastic anemia due to poor intake of vitamin B12 and a literature review on the topic(AU)