A New Case of Association of Megaloblastic Anemia and Pancytopenia of Infants.

BACKGROUND: Vitamin B12, or cobalamin deficiency, an infrequent clinical entity in pediatric age, is found almost solely in breastfed infants whose mothers are purely vegetarian, non-supplemented or with pernicious anemia. Megaloblastic anemia in infants presents with generalized weakness or irritability. METHODS: Diagnosis is usually centered on complete blood count, vitamin dosing, and peripheral smear, which may show macrocytes, hypersegmented neutrophils, reticulocytopenia and a raised mean corpuscular volume (MCV ˃ 100 fL). Pancytopenia has also been noted. RESULTS: We report an exclusive breastfed nine-month-old female child who presented with irritability, developmental delay, and difficulties in introducing new foods. Her initial blood count revealed pancytopenia. Vitamin B12 levels were found to be reduced. Maternal levels of Vitamin B12 were also found to be borderline low. The child was treated as per protocols, and improvement was evidenced with the return of hematological parameters to the regular and gradual advancement of milestones. CONCLUSIONS: We aim to underscore the importance of megaloblastic anemia as an important and rare cause of anemia in infancy.

Flow cytometry-detected changes in megaloblastic anemia secondary to cobalamin deficiency.

Introduction: Megaloblastic anemias secondary to Vitamin B12 deficiency are a group of pathologies produced by defective nuclear DNA synthesis. Objective: To describe the maturation alterations found in hematopoietic precursors of the bone marrow in a series of patients with megaloblastic anemia. Methods: Were included patients attended at the Regional Hospital of Concepción with bone marrow samples sent for the study of cytopenia by flow cytometry whose final diagnosis was megaloblastic anemia. The immunophenotype was performed with CD45, CD34, CD117, HLA-DR, markers of neutrophil (CD13, CD11b, CD10, CD16) and/or erythroblast (CD105, CD71, CD36) maturation. Results: From the flow cytometry laboratory database, 8 patients with megaloblastic anemia were identified, and myelodysplastic syndromes (n=9) and normal or reactive bone marrow (n=10) were used as controls. 44% were men, with a median age of 58 years. Megaloblastic anemia was associated with a higher proportion of size and complexity of erythroid and myeloid progenitors compared to lymphocytes compared to controls. The total percentage of erythroblasts and the proportion of CD34+ myeloid cells associated with erythroid lineage was higher in megaloblastic anemia, associated with a maturation arrest in the CD105+ precursor stage (69% vs 19% and 23%, p<0.001). The heterogeneity of CD36 and CD71 in megaloblastic anemia was similar to myelodysplastic syndromes. Conclusions: Megaloblastic anemia produces a heterogeneous involvement of hematopoiesis, characterized by a greater size and cellular complexity of precursors of the neutrophil and erythroid series and a maturation arrest of the erythroblasts.

Introducción: Anemias megaloblásticas secundarias a la deficiencia de vitamina B12 son patologías producidas por una síntesis defectuosa del ADN nuclear. Objetivo: Describir las alteraciones madurativas encontradas en precursores hematopoyéticos de la médula ósea de una serie de pacientes con anemia megaloblástica. Métodos: Se incluyeron pacientes atendidos en el Hospital Regional de Concepción con muestras de médula ósea enviadas para estudio de citopenias por citometría de flujo cuyo diagnóstico fue anemia megaloblástica. El inmunofenotipo se realizó con CD45, CD34, CD117, HLA-DR, marcadores de maduración de serie de neutrófilo (CD13, CD11b, CD10, CD16) y/o eritroblasto (CD105, CD71, CD36). Resultados: Se identificaron 8 pacientes con anemia megaloblástica y como controles se utilizaron síndromes mielodisplásicos (n=9) y médula ósea normal o reactiva (n=10). El 44% eran hombres, con una mediana de edad de 58 años. La anemia megaloblástica se asoció con una mayor proporción de tamaño y complejidad de progenitores eritroides y mieloides con respecto de los linfocitos en comparación a los controles. El porcentaje total de eritroblastos y la proporción de células mieloides CD34+ comprometidas con el linaje eritroide fue mayor en anemia megaloblástica, asociado a una parada madurativa en la etapa de precursor CD105+ (69% vs 19% y 23%, p <0.001). La heterogeneidad de CD36 y CD71 en anemia megaloblástica fue similar a los síndromes mielodisplásicos. Conclusiones: la anemia megaloblástica produce una afectación heterogénea de la hematopoyesis, caracterizada por un mayor tamaño y complejidad celulares de precursores de la serie neutrófilo y eritroide y una detención madurativa de los eritroblastos.

An infantile case of hereditary folate malabsorption with sudden development of pulmonary hemorrhage: a case report.

BACKGROUND: Hereditary folate malabsorption-a rare disorder caused by impairment of the folate transporter-can develop into severe folate deficiency manifesting as megaloblastic anemia and occasionally thrombocytopenia. Reportedly, megaloblastic anemia can manifest with hemorrhagic episodes, possibly due to ineffective platelet production and platelet dysfunction. However, life-threatening hemorrhage events in hereditary folate malabsorption have not been well investigated. CASE PRESENTATION: A 3-month-old Japanese boy was transferred to our hospital due to thrombocytopenia and severe megaloblastic anemia. During a thorough examination of hematopoietic abnormalities, the patient suddenly went into cardiac arrest due to pulmonary hemorrhage. Although intravenous folate supplementation was started soon after the identification of folate deficiency, the patient died of circulatory defect and multiple organ failure. The cause of pulmonary hemorrhage, such as respiratory infection, could not be confirmed. Genetic investigation revealed a mutation in the SLC46A1 gene to be the cause of the hereditary folate malabsorption. CONCLUSION: We report an infantile case of hereditary folate malabsorption that progressed to lethal pulmonary hemorrhage before folate deficiency was identified. Clinicians should consider that megaloblastic anemia could lead to severe bleeding without warning, and that nutrient supplementation should be initiated as soon as possible.

How I investigate acquired megaloblastic anemia.

In this review of megaloblastic anemia (MA), an overview of vitamin B12 and folate body requirements, biochemical pathways, and laboratory testing strategies will be provided. However, the focus of this review is the classic and unique features of MA in blood and bone marrow. Acquired MA is a benign disorder for many, but can be detrimental for some. The clinical presentation can vary considerably, and the spectrum of symptoms and signs is diverse and quite broad. Prompt recognition and therapy are critical to prevent potential irreversible damage and clinical sequelae, especially in patients with vitamin B12 deficiency. A delay in diagnosis of vitamin B12 deficiency can result in significant neurologic sequelae that may not fully resolve with treatment, including in neonates and young infants. The blood and bone marrow features in MA can closely mimic thrombocytopenic purpura, myelodysplasia, and other myeloid neoplasms. Both pancytopenia and normal MCV at presentation are common in MA and raise unique challenges for the diagnostician. Partially treated MA is also a significant diagnostic "trap". MA is highly responsive to treatment, and patients tend to improve rapidly upon treatment initiation. However, the broad range of clinical and hematologic features makes the rapid, successful diagnosis of MA a unique challenge for the hematopathologist. Even in the era of state-of-the-art laboratory testing, a high suspicion is required.

A Brief Review on Vitamin B12 Deficiency Looking at Some Case Study Reports in Adults.

In the era of evidence-based medicine, the randomized clinical trial corresponds to the top step in the qualitative scale of the evidence available in the literature, while small series of cases or the description of individual cases occupy the last place. However, the latter represent an important part of clinical practice and have significantly influenced the evolution of medicine, contributing significantly to the advancement of scientific knowledge. Vitamin B12 deficiency shares several common symptoms that affect several tissues and organs with health aliments, so its diagnosis could be unobvious for the broad array of its effects and investigation methods used. In this review, we focused our attention on some case reports related to the vitamin B12 deficiency associated to anemia, neurologic disorders, and hyperhomocysteinemia. B12 deficiency reversal is simply achieved by prompt therapy, even though it is not the same for several disorders.

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.

Vitamin B12 Deficiency Resembling Acute Leukemia: A Case Report.

Vitamin B12 deficiency in children can cause megaloblastic anemia, poor growth, and increased chances of infections. It is an important reversible cause of bone marrow suppression which at the time of presentation can mimic hematological malignancy. Therefore, it should be considered as a differential diagnosis in cases suspected of acute leukemia. We report a case of 14 months old child who had atypical presentation of vitamin B12 deficiency. He had chronic fever, decreased feeding and increased paleness for one year. Pancytopenia with severe anemia was present along with 19% reactive/atypical cells in peripheral blood smear suggesting acute leukemia. However, bone marrow aspiration and biopsy showed features of megaloblastic anemia. Vitamin B12 level measured was very low and treatment with cyanocobalamin caused drastic improvement in the child's condition.

Megaloblastic anaemia in a 9-weeks old infant: A case report.

Megaloblastic anaemia due to vitamin B12 and folic acid deficiency is uncommon in infancy and rarely reported in infants below 3 months of age. We hereby report a case of megaloblastic anaemia in a 9-weeks old infant having fever from 7th week of life. Blood picture showed pancytopenia and diagnosis was confirmed on bone marrow biopsy and serum level of vitamins. Patient positively responded to vitamin B12 and folic acid supplementation. Infants with pancytopenia even younger than 2 months, should also be investigated for vitamin B12 and folate deficiency. Mother of the baby was not antenatally investigated for anaemia. Prompt antenatal diagnosis and treatment of mothers can reduce the incidence in the infants.

Vitamin B12 deficiency as a cause of severe neurological symptoms in breast fed infant - a case report.

BACKGROUND: Vitamin B12 (cobalamin, cbl) deficiency in children is rare and may occurs in exclusively breast fed infants of mothers on vegetarian or vegan diet with lack of appropriate supplementation. The clinical manifestation of vitamin B12 deficiency include neurological disorders, megaloblastic anemia and failure to thrive. Routine and commonly used laboratory tests such as cell blood count (CBC) or serum vitamin B12 level are sufficient for appropriate diagnosis. Typical therapy is based on intramuscular cobalamin injections. Early diagnosis and early onset of treatment are crucial factors for long-term prognosis of patients as the duration of deficiency may be correlated with the development of long lasting changes in the nervous system. The purpose of this article is to present influence of maternal vitamin B12 deficiency as a cause of infant psychomotor retardation. CASE PRESENTATION: We report the case of a 7 months old girl whose parents sought medical advice due to pathological somnolence and developmental regression of their daughter with onset approximately 2 months prior to the visit. Following several diagnostic tests it was determined that the infant's symptoms were due to vitamin B12 deficiency which was secondary to the mother's latent Addison-Biermer disease. Apart from neurological symptoms the infant also showed megaloblastic anemia which is typical to cobalamin deficiencies. Intramuscular vitamin B12 supplementation resulted in instant improvement of the patient's general condition and blood morphology. Unfortunately, psychological examination indicated long-term psychomotor retardation due to delayed diagnosis of B12 deficiency. CONCLUSIONS: Vitamin B12 levels should be considered during differential diagnosis of neurological symptoms in exclusively breast-fed infants especially if they co-exist with megaloblastic anemia and psychomotor retardation.

Severe megaloblastic anemia: Vitamin deficiency and other causes.

Megaloblastic anemia causes macrocytic anemia from ineffective red blood cell production and intramedullary hemolysis. The most common causes are folate (vitamin B9) deficiency and cobalamin (vitamin B12) deficiency. Megaloblastic anemia can be diagnosed based on characteristic morphologic and laboratory findings. However, other benign and neoplastic diseases need to be considered, particularly in severe cases. Therapy involves treating the underlying cause-eg, with vitamin supplementation in cases of deficiency, or with discontinuation of a suspected medication.

Vitamin B12 Deficiency Anemia and Polyneuropathy Due to Chronic Radiation Enteritis.

A 62-year-old Japanese woman developed numbness of the extremities and megaloblastic anemia. She had undergone total abdominal hysterectomy, whole-pelvis radiation therapy and chemotherapy for gynecological cancer 10 years before. Chronic abdominal pain, diarrhea and intermittent small-bowel obstruction had afflicted her for a long time. We diagnosed her with vitamin B12 deficiency anemia and polyneuropathy due to chronic radiation enteritis causing malabsorption. Vitamin B12 injections improved her numbness and anemia. The early diagnosis and treatment of deficiency of vitamin B12 are important. Physicians should regularly measure vitamin B12 levels and supplement vitamin B12 as needed in patients with chronic radiation enteritis.

[Hyperpigmentation due to Vitamin B12 Deficiency].

Vitamin B12 deficiency is associated with mucocutaneous symptoms, such as glossitis and hyperpigmentation, as well as megaloblastic anemia and neuropathy. These are reversible conditions, and the symptoms improve with early detection and treatment. Whenever anemia is encountered in routine practice, vitamin B12 deficiency should be considered and the presence of skin symptoms should be investigated.

CA 15-3 predicting breast cancer relapse: beware of vitamin B12 deficiency.

A sustained increase of cancer antigen 15-3 serum levels was found in a 54-year-old woman treated 2 years ago for early stage breast cancer, without any evidence of cancer recurrence. The patient thereafter developed severe megaloblastic anemia secondary to vitamin B12 deficiency. Supplementation with B12 to reverse the anemia led to the normalization of the cancer antigen 15-3 serum levels. As such, with the limited understanding of molecular biology, the integrative approach of clinical history, physical examination, and diagnostic imaging remain pivotal in the management of cancer patients.