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.

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.

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.

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.

Vitamina B12: ¿para algo más que el tratamiento de la anemia megaloblástica? / Vitamin B12: For more than just the treatment of megaloblastic anemia?

Vitamin B12, or cobalamin, belongs to the group of water-soluble vitamins and is ingested through food of animal origin such as eggs, milk, red meat and poultry, fish, and shellfish. Its clinical indication is the treatment of hypovitaminosis B12 administered orally or intramuscularly in the form of hydroxocobalamin. Hypovitaminosis B12 is mainly caused by deficient dietary intake (individuals with malnutrition, vegetarians or vegans, older adults, pregnant people, individuals with alcohol use disorder); when intestinal absorption is reduced (atrophic gastritis, malabsorption syndrome, gastrointestinal surgery); and for causes associated with the intake of drugs (antacids, metformin). Hypervitaminosis B12 has been associated with renal failure; liver diseases such as cirrhosis and acute-phase hepatitis; alcohol use disorder with or without liver involvement; solid tumors of the lung, liver, esophagus, pancreas, and colorectum; and in hematological malignancies such as leukemia and bone marrow dysplasia (AU)

La vitamina B12 o cobalamina pertenece al grupo de vitaminas hidrosolubles y su aporte se realiza a través de la ingesta de alimentos de origen animal como huevo; leche; carnes rojas y de aves; pescados y mariscos. Su indicación clínica es el tratamiento de la hipovitaminosis B12 administrada por vía oral o intramuscular en forma de hidroxicobalamina. La hipovitaminosis B12 se origina, principalmente, por un déficit de aporte en la dieta (malnutrición, sujetos vegetarianos o veganos, ancianos, embarazo, alcoholismo); cuando está disminuida su absorción intestinal (gastritis atrófica, síndrome de malabsorción intestinal, cirugía gastro-intestinal) y asociada a ingesta de fármacos (antiácidos, metformina). La hipervitaminosis B12 se ha relacionado con la insuficiencia renal; hepatopatías como cirrosis y hepatitis en fase aguda; alcoholismo con o sin afectación hepática; tumores sólidos de pulmón, hígado, esófago, páncreas y colorrectal y en neoplasias hematológicas como leucemia y la displasia medular (AU)

Aspectos esenciales sobre vitamina B12 / B12 vitamin, essential aspects

Se citan las fuentes alimentarias más convencionales para satisfacer los requerimientos nutricionales, las condiciones necesarias para la absorción de la vitamina B12 a nivel del intestino delgado, así como los factores que pueden interferir en su absorción, se hace referencia al órgano que se encarga de su almacenamiento y requerimientos diarios. Se exponen también las funciones además de las manifestaciones del estado carencial, fundamentalmente a nivel del sistema nervioso (AU)

More conventional food sources are cited to meet nutritional requirements, the necessary conditions for the absorption of vitamin B12 in the small intestine, as well as the factors that can be interfered with its absorption and referring to the body which is responsible for its storage and daily requirements. The report also presents further features of the manifestations of deficiency state, mainly at the level of the nervous system

Manejo, prevención y control de la anemia perniciosa / Management, prevention and control of pernicious anemia

La anemia perniciosa es la causa más frecuente de anemia megaloblástica en nuestro medio y es consecuencia de una deficiencia de vitamina B12 debido a su vez a la disminución o ausencia de factor intrínseco (FI) por atrofia de la mucosa gástrica o por destrucción autoinmune de las células parietales productoras de éste. Ante la existencia de una atrofia gástrica intensa, se origina un descenso en la producción de ácido y FI y una posterior alteración en la absorción de vitamina B12. En un 50% de los casos se asocia a anticuerpos anti FI, cuya presencia en otras enfermedades auto-inmunes es excepcional. En pacientes con anemia perniciosa la determinación de anticuerpos anti FI tiene una alta especificidad (95%), sin embargo, la determinación de anticuerpos anticélulas parietales cuentan con una especificidad baja. El tratamiento de elección es la administración de B12 intramuscularmente. La pauta consiste en administrar 1 mg. de Vitamina B12 diariamente durante una semana, posteriormente semanal durante un mes y después cada 2-3 meses de por vida (AU)

Pernicious anemia is the most frequent cause of megaloblastic anemia in our area, and it is the result of a vitamin B12 deficiency due, itself, to the de-crease or absence of intrinsic factor (IF) because of gastric mucosa atrophy or autoimmune destruction of IF-producing parietal cells. With the existence of a severe gastric atrophy, there is a decrease in acid and IF production and a further change in vitamin B12 absorption. Fifty percent of the cases are associated to anti-IF antibodies, which presence in other autoimmune diseases is exceptional. In patients with pernicious anemia, measurement of anti-IF antibodies has high specificity (95%); however, measurement of anti-parietal cells antibodies has low specificity. The first-choice treatment is adminis-tration of vitamin B12 intramuscularly. The regimen is the administration of 1 mg of vitamin B12 daily for one week, weekly thereafter for one month and, then, every 2-3 months for life (AU)

Degeneración combinada subaguda medular, una complicación infrecuente de un problema frecuente en la práctica clínica: el déficit de vitamina B12 / Subacute combined degeneration of spinal cord, an uncommon complication of a frequent problem in the clinical practice: vitamin B12 deficiency

La anemia megaloblástica por déficit de vitamina B12 es una enfermedad muy prevalente en nuestro medio. Presentamos el caso de un paciente con una degeneración combinada subaguda medular, un caso raro de complicación del déficit de vitamina B12. Es importante recordar la importancia de un correcto tratamiento de la deficiencia de cobalamina por su importante efecto deletéreo sobre el sistema nervioso central y por sus secuelas neurológicas si no se instaura el tratamiento a tiempo. A pesar de que la práctica habitual en España es el tratamiento intramuscular, diversos estudios demuestran que el tratamiento por vía oral del déficit de la vitamina B12 es igual de efectivo, con mejor aceptación por el paciente y de menor coste (AU)

Megaloblastic anemia due to vitamin B12 deficiency is a very common clinical problem. We present the case of a male patient with combined degeneration of the spinal cord, a rare complication of vitamin B12 deficiency. It is essential to remember the importance of correct treatment of vitamin B12 deficiency due to the significant harmful effect it has on the central nervous system and neurological sequels if treatment is not begun on time. Although the usual practice in Spain is to use intramuscular administration, several studies show that oral treatment of the vitamin B12 deficiency is effective and has better acceptance by the patient as well as lower cost (AU)

Tratamiento oral con cobalamina: una nota de precaución / Oral cobalamine therapy: a note of caution

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Anemia megaloblástica / Megaloblastic anemia

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Tratamiento oral con cobalamina en la anemia megaloblástica / Oral treatment of megaloblastic anemia with cobalamin

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Anemia megaloblástica / Megaloblastic anemia

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Anemia megaloblastica en el Hospital 2 de Mayo: agosto 1984 - abril 1987 / Megaloblastic anemia in the Hospital 2 de Mayo: August 1984 - april 1987

Se estudian 34 casos de Anemia Megaloblástica por deficiencia de vitamina B12 y/o ácida fólico, atendido a diferentes parámetros hematológicos, bioquímicos, clínicos y otros datos complementarios comparando los resultados obtenidos con lo publicado en la literatura médica. Los datos más relevantes que se ha obtenido se pueden concretar diciendo que la Anemia Megaloblástica es una enfermedad de ligero predominio femenino y con preferencias por las edades avanzadas. Las manifestaciones de anemia son las alteraciones clínicas más frecuentemente encontradas. Se trata generalmente de anemias marcadas acompañadas de discretas leucopenia y trombocitopenia. En nuestro medio se tipifica la etiología y a todos los pacientes se les trata con la administración simultánea de vitamina B12 y ácido fólico. La incidencia real de esta anemia es difícil de establecer, puesto que los tratamientos polivitamínicos administrados muchas veces de forma indiscriminada pueden enmascarar un número elevado de casos, sobre todo en el ámbito extrahospitalario

Megaloblastic anaemia of infancy in Jamaica

The terms "megaloblast" and "megaloblastic anaemia" are defined. The megaloblast is a pathological cell and it is only found, specifically, in anaemias which are attributable to a deficiency of certain essential haemopoietic factors present in liver. The morphology of normoblasts and of megaloblasts, i.e. a cell with some of the characteristics of both a megaloblast and a normoblast, is discussed. The charateristic changes in the granulocytic series of cells, which are seen in megaloblastic anaemias, are discussed. The development of knowledge with regard to the essential haemopoietic factors present in liver is described, and the possible roles, and interrelationships of folic acid, folinic acid and vitamin B12 are discussed. It is concluded that, although their precise functions are still uncertain, there is no doubt as to their importance in nucleic acid synthesis. The literature on megaloblastic anaemia of infancy is reviewed. The rather rare association between infantile malnutrition and megaloblastic anaemia are discussed, and the fact that anaemia of any severe degree is unusual in kwashiorkor is stressed. The few available bone-marrow studies in kwashiorkor are described. A megaloblastic bone marrow has not very commonly been seen in kwashiorkor except in Durban, South Africa. A condition which resembles kwashiorkor very closely has been reported from Sicily. These infants are often very anaemic and a megaloblastic bone marrow is commonly seen. The clinical, haematological and other laboratory findings on fifty cases of megaloblastic anaemia of infancy are presented. From the clinical point of view the most striking feature was that all the infants were very malnourished and grossly under-weight. On haematological examination the best valuable finding from a diagnostic point of view was found to be the haemoglobin level. If this is below 7.0 g percent the anaemia is almost certainly going to be megaloblastic. A full blood count with determination of mean corpuscular volume, and haemoglobin concentration is rarely helpful since the anaemia is usually normocytic and normochronic. A certain diagnosis can be made by bone marrow puncture. Of the 50 cases, 45 were tested with folic acid, and 5 received vitamin B12. Six of the folic acid treated cases died. In the 39 folic acid treated who recovered, the haematological and clinical response was excellent. The 5 cases treated with vitamin B12 also showed a good haemotological and clinical response, although the dosage used was large. The majority of cases received antibiotics, and some received several, but in no case was a haematological response observed. The morphology of the bone marrow in haemaloblastic anaemia of infancy is described and extensively illustrated. In addition to typical megaloblasts, erythroblasts of intermediate type were commonly observed. The characteristic white cell abnormalities are also described. Changes in the nuclear chromatin structure of the megakaryocytes were also noted, which resemble the changes seen in megaloblasts quite closely. The post-mortem findings in the six fetal cases are summarized. Extramedullary erythropoiesis was observed in the livers of three cases, and in two a severe chronic fatty change was presented. In one case an acute fatty change was seen. The results of liver biopsies carried out on twelve other infants are also reported. Extra-medullary erythropoiesis was found in seven out of the ten specimens which were sectioned histologically. This finding of extra-medullary erythropoiesis is regarded as being pathognomonic of the disease, although it is not invariably present. Five cases of sickle cell anaemia with associated megaloblastic anaemia are described. This association has only been reported once before in infancy. Three other instances are recorded in the literature in older children. The association is highly significant, since a total of five cases out of fifty exceeds the expected incidence by no less than 3 times. An unexpected and unexplained finding was that three of these cases were also demonstrably iron deficient. The pathogenesis of the disease is considered in detail. It is thought that dietary deficiency is the most important factor, but whether of folic acid or vitamin B12 is uncertain. A deficiency of folic acid seems more likely. The possible significance of ascorbic acid deficiency in the aetiology of the disease is discussed, and the literature on the experimental production of megaloblastic anaemia in monkeys by means of a diet low in folic acid and deficient in ascorbic acid is reviewed. Only one infant in the present series had frank scurvy, and in this case ascorbic acid was required in addition to folic acid to produce a satisfactory haematological and clinical response. The importance of infection in the causation of the disease is discussed. Infections of various types were extremely common especially upper respiratory infections and gastro-enteritis. The role of gastro-enteritis is illustrated by six case in which specific pathogens were isolated from the stools. The possible mechanisms, which may be of importance in the causation of the disease, are listed: (1) A dietary deficiency of haemopoietic substance is thought to be the most significant factor. (2) An intrinsic factor deficiency is suggested speculatively as possibly playing a part. (3) Impaired absorption of haemopoietic factors due to diarrhoea is undoubtedly important. (4) Excessive utilization of haemopoietic factors by an abnormal bacterial flora in the intestine may contribute to a deficiency. (5) Diminished synthesis of haemopoietic factors by an abnormal bacterial flora in the intestine may also play a part. In conclusion some possible lines of future investigation of the disease are discussed (Summary)