Tropical sprue in megaloblastic anemia

Background: The causes of megaloblastic anemia may vary in different geographical regions. The aim of the present study is to evaluate the utilization of bone marrow examination and upper gastrointestinal endoscopy (UGIE) in megaloblastic anemia.Methods: This was a cross-sectional descriptive study done on 50 patients (age ≥15years) of macrocytic anemia after applying inclusion and exclusion criteria. A bone marrow aspiration with biopsy and an UGIE with duodenal biopsy were performed in consented patients with evidence of megaloblastic anemia in the peripheral smear or Vitamin B12 deficiency or folate deficiency or both.Results: Out of 50 cases, 38 patients had pure Vitamin B12 deficiency, 2 patients had pure folate deficiency and 5 patients had combined deficiency. Among 43 patients with vitamin B12 deficiency, only four (9.3%) were vegetarians and remaining 39 (90.7%) were having non-vegetarian diet. Bone marrow study was done in 29 patients (out of 50) and all of them were found to have megaloblastic erythropoiesis in the bone marrow. Thirty three out of 50 consented for UGIE and duodenal biopsy. Out of 33, 17 patients (51.5%) had features of tropical sprue in biopsy.Conclusions: We found a high prevalence of tropical sprue in megaloblastic anemia due to Vitamin B12 and/or folate deficiency. We recommend that UGIE with deep duodenal biopsy should be considered in all patients with megaloblastic anemia to rule out tropical sprue in India.

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Hematologic Manifestations of Vitamin B12 Deficiency in Swine

Blood ◽

10.1182/blood.v6.10.867.867 ◽

1951 ◽

Vol 6 (10) ◽

pp. 867-891 ◽

Cited By ~ 8

Author(s):

G. E. CARTWRIGHT ◽

BETTY TATTING ◽

JEAN ROBINSON ◽

N. M. FELLOWS ◽

F. D. GUNN ◽

...

Keyword(s):

Bone Marrow ◽

Vitamin B12 ◽

Liver Damage ◽

Megaloblastic Anemia ◽

Macrocytic Anemia ◽

Vitamin B12 Deficiency ◽

Deficiency Anemia ◽

Severe Neutropenia ◽

Pteroylglutamic Acid ◽

B12 Deficiency

Abstract In an effort to produce a deficiency of vitamin B12 a total of 70 pigs were fed a purified diet containing soybean alpha protein in place of casein. One group of animals was started on the diet at 2 to 7 days of age. A second group began at 21 to 28 days of age. Methionine, iodinate casein, desiccated thyroid and pteroylglutamic acid were added to the diet of certain animals and! omitted from the diet of other pigs. In addition, 9 pigs were gastrectomized. Forty-three of the animals survived for a sufficiently long period of time for adequate evaluation of the results of the experiment. Severe liver damage was observed in 24 of the 25 animals autopsied. The only animal not showing liver damage received vitamin B12 from the beginning of the experiment. Necrosis of the liver cells, fatty infiltration, or both, occurred in the presence of a high fat diet containing apparently adequate amounts of protein, choline, vitamin E and methionine. These pathologic changes were apparently prevented but not reversed by the administration of vitamin B12. Growth of the animals on the above diets without added vitamin B12 was retarded as compared with the growth of animals on the same diet supplemented with this vitamin. The administration of vitamin B12 to the deficient animals resulted in rapid growth. Of the 39 animals not receiving vitamin B12 13 failed to develop anemia, 16 developed a mild anemia and in 10 a moderately severe anemia was present. When present the anemia was normocytic and in 24 pigs was accompanied by a moderately severe neutropenia. Differential cell counts on the sternal marrow were normal except for a slight increase in the proportion of normoblasts. These hematologic alterations were neither consistently or completely corrected by the administration of vitamin B12 in spite of the fact that definite and sometimes marked reticulocyte increases followed. When methionine deficiency was associated with vitamin B12 deficiency, anemia appeared to be more severe. The administration of aureomycin, an "animal protein factor," did not stimulate growth and failed to induce a hemopoietic response. There was no macrocytic anemia, the bone marrow was not megaloblastic, and neurologic disturbances or morphologic alterations in the neutrophils were not observed. These results are in contrast to those obtained in pigs with an experimentally produced deficiency of pteroylglutamic acid. Such animals develop macrocytic anemia, leukopenia and a macronormoblastic type of bone marrow. It is not possible to give with any assurance the reason why megaloblastic anemia was not produced in the "B12-deficient" animals. This may have been due to the fact that (1) the deficiency was not sufficiently severe to result in such a change in the hemopoietic system; or (2) because pteroylglutamic acid prevents the development of megaloblastic anemia even in the absence of vitamin B12.

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The Value of Duodenal Biopsies in the Evaluation of Megaloblastic Anemia

Journal of Laboratory Physicians ◽

10.1055/s-0041-1730817 ◽

2021 ◽

Author(s):

Nasrin Nisha N. ◽

Sakthisankari Shanmugasundaram ◽

Kartikayan R. K.

Keyword(s):

Bone Marrow ◽

Vitamin B12 ◽

Megaloblastic Anemia ◽

Serum Vitamin ◽

Folate Deficiency ◽

Duodenal Biopsy ◽

Tropical Sprue ◽

Bone Marrow Biopsies ◽

Endoscopic Findings ◽

Duodenal Biopsies

Abstract Introduction Megaloblastic anemia is one of the common causes of anemia in India. Duodenal biopsies are routinely performed in the investigation of megaloblastic anemia. The present study was undertaken to analyze the value of duodenal biopsy in megaloblastic anemia and to correlate endoscopic findings with biopsy. As a secondary aim, the study has also analyzed the hematological profile and vitamin B12 and folate status of these patients. Materials and methods All the cases of megaloblastic anemia with bone marrow studies diagnosed at PSG Institute of Medical Sciences and Research during the two year period from January 2016 to December 2017 were retrieved. Clinical and laboratory findings (serum vitamin B12 and folate levels) and endoscopic findings were retrieved from hospital records of the patients. Duodenal biopsies of these patients reported in the histopathology department were retrieved and reviewed. Statistical analysis was done using SPSS software 20.0. Results There were 93 cases of megaloblastic anemia diagnosed on bone marrow biopsies. Tropical sprue was diagnosed in 49.5% of cases, followed by intraepithelial lymphocytosis (17.2%), peptic duodenitis (17.2%), and no significant pathology in 16% of cases. Pancytopenia was present in 54.8% of cases. Isolated vitamin B12 deficiency including low levels was present in 48.38% and folate deficiency was seen in 4.3% cases; 34.48% cases had both vitamin B12 and folate deficiency. Conclusion The incidence of tropical sprue in megaloblastic anemia is 49.5% in the study. Duodenal biopsy is valuable in the work up of megaloblastic anemia, irrespective of the endoscopic changes in identifying the etiology.

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Development delay in children with severe acute malnutrition and its association with Vitamin B12 deficiency

International Journal of Contemporary Pediatrics ◽

10.18203/2349-3291.ijcp20194721 ◽

2019 ◽

Vol 6 (6) ◽

pp. 2484

Author(s):

Aishvarya Adhualia ◽

Manisha Maurya ◽

A. D. Tewari

Keyword(s):

Vitamin B12 ◽

Developmental Delay ◽

Complete Blood Count ◽

Severe Acute Malnutrition ◽

Megaloblastic Anemia ◽

Macrocytic Anemia ◽

Vitamin B12 Deficiency ◽

Acute Malnutrition ◽

Rehabilitation Centre ◽

B12 Deficiency

Background: About half of the under five children are malnourished in India and so is morbidity associated with it. Malnutrition is also associated with multiple vitamin deficiency one of which is vitamin B12. Vitamin B12 is essential for DNA, RNA and protein synthesis; and for myelination of brain during the early childhood period. Deficiency of vitamin B12 can lead to megaloblastic anemia and neurological problems. So, authors aimed to look prevalence of vitamin B12 deficiency and; its hematological and neurological effects in severe acute malnourished children.Methods: it was an observational case control study, in which severe acute malnourished (SAM) children aged 0- 59 months who were admitted in Nutritional Rehabilitation Centre (NRC) were enrolled. Vitamin B12 levels were estimated and levels <200 pg/ml, 200-350 pg/ml, and >350 pg/ml were considered deficient, insufficiency and sufficient. Complete blood count was done for hematological effects and; developmental assessment was done to look for neurological effects.Results: Vitamin B12 was deficient, insufficient, normal in 15(16.3%), 25 (27.5%) and 52 (56.5%) children respectively. Vitamin B12 deficiency was significantly associated with hyperpigmentation and glossitis. Infant and young child feeding practices were not associated vitamin B12 deficiency. Macrocytic anemia was found in 23.4% SAM children and macrocytosis was not significantly associated with vitamin B12 deficiency. Developmental delay was found in 55.3 % children and was not significantly associated with severe acute malnutrition. Conclusions: There is high prevalence of Vitamin B12 deficiency and insufficiency in children with severe acute malnourished children. Macrocytic anemia and developmental delay are not significantly associated with vitamin B12 deficiency.

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The effect of folate analogues and vitamin B12 on provision of thymine nucleotides for DNA synthesis in megaloblastic anemia

Blood ◽

10.1182/blood.v59.3.634.bloodjournal593634 ◽

1982 ◽

Vol 59 (3) ◽

pp. 634-640

Author(s):

MR Taheri ◽

RG Wickremasinghe ◽

BF Jackson ◽

AV Hoffbrand

Keyword(s):

Vitamin B12 ◽

De Novo ◽

Megaloblastic Anemia ◽

Vitamin B12 Deficiency ◽

Folate Deficiency ◽

Minor Role ◽

B12 Deficiency ◽

Thymidylate Synthesis ◽

Marrow Cells

The role of vitamin B12 in the folate dependent biosynthesis of thymidine nucleotides is controversial. In an attempt to clarify this, three methods have been used to assess the relative efficacy of vitamin B12 (hydroxocobalamin) and various folate analogues in titrated concentrations at correcting ‘de novo’ thymidylate synthesis by megaloblastic human marrow cells: (1) The deoxyuridine (dU) suppression test which analyses the reduction in (3H)-thymidine labeling of DNA by unlabeled dU. Marrow cells were also labeled with (6–3H)-dU with assessment of (2) its incorporation into DNA and (3) the accumulation of (6–3H)-deoxyuridine monophosphate (3H-dUMP). The three methods gave similar results. In both, N6-formyl tetrahydrofolate (formyl-FH4) was the most effective agent at correcting thymidylate synthesis in megaloblastic anemia due to vitamin B12 or folate deficiency. Vitamin B12 corrected the lesion in vitamin B12 deficiency but not in folate deficiency. Tetrahydrofolate (FH4) and folic acid were effective in deficiency of vitamin B12 or folate, although in both deficiencies they were less effective than formyl-FH4. Methyl-FH4 was effective in folate deficiency but not in vitamin B12 deficiency. These results confirm the failure of methyl-FH4 utilisation in vitamin B12 deficiency. They suggest that if vitamin B12 is needed in the formylation of FH4, this is a minor role in provision of the correct coenzyme for thymidylate synthesis compared with its major role of provision of FH4 from methyl- FH4.

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Hematogones Detected by Flow Cytometry in a Child with Vitamin B12 Deficiency

Pediatric and Developmental Pathology ◽

10.1177/1093526616686241 ◽

2017 ◽

Vol 20 (2) ◽

pp. 172-175

Author(s):

Lisa Sutton ◽

Nkechi Mba

Keyword(s):

Bone Marrow ◽

Flow Cytometry ◽

Acute Leukemia ◽

Vitamin B12 ◽

Megaloblastic Anemia ◽

Bone Marrow Failure ◽

Vitamin B12 Deficiency ◽

Bone Marrow Biopsies ◽

B12 Deficiency ◽

B Cell Precursors

Vitamin B12 deficiency is a known cause of megaloblastic anemia and bone marrow failure. Bone marrow biopsies are not frequently performed as part of the diagnostic workup and can demonstrate morphologic features that overlap with myelodysplastic syndrome (MDS) and acute leukemia. We describe a case of a dysplastic bone marrow with increased bone marrow hematogones detected by flow cytometry in a child with vitamin B12 deficiency. Hematogones are normal B cell precursors, and hyperplasia has been described in a variety of often reactive conditions and also disease. Hematogones are not typically seen in MDS. The presence of hematogones may help differentiate the dysplastic changes seen in vitamin B12 deficiency from MDS.

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5-Methyltetrahydrofolate related enzymes and DNA polymerase alpha activities in bone marrow cells from patients with vitamin B12 deficient megaloblastic anemia

Blood ◽

10.1182/blood.v59.4.832.bloodjournal594832 ◽

1982 ◽

Vol 59 (4) ◽

pp. 832-837

Author(s):

Y Kano ◽

S Sakamoto ◽

K Hida ◽

K Suda ◽

F Takaku

Keyword(s):

Bone Marrow ◽

Vitamin B12 ◽

Dna Polymerase ◽

Methylenetetrahydrofolate Reductase ◽

Bone Marrow Cells ◽

Megaloblastic Anemia ◽

Vitamin B12 Deficiency ◽

Dna Polymerase Alpha ◽

B12 Deficiency ◽

Marrow Cells

The activities of 5-methyltetrahydrofolate (5-CH3THF) related enzymes and DNA polymerase alpha were determined in bone marrow cells obtained from patients with vitamin B12 deficient megaloblastic anemia and compared with those from healthy volunteers and patients with hemolytic anemia. 5-CH3THF homocysteine methyltransferase activity was significantly lower than that in the control subjects. 5,10- methylenetetrahydrofolate reductase activity was only slightly elevated to that in the control subjects. DNA polymerase alpha activity was significantly higher than that in the control. High deoxyuridine suppression test values in vitamin B12 deficient bone marrow cells were improved by tetrahydrofolate, but not by 5-CH3THF. These data indicate that, even though the reverse reaction catalyzed by 5,10- methylenetetrahydrofolate reductase may be operative in vitamin B12 deficiency, it is not sufficient to correct the disturbance in folate metabolism in vitamin B12 deficiency. Increased DNA polymerase alpha activity may be due to compensation for disarranged DNA synthesis.

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5-Methyltetrahydrofolate related enzymes and DNA polymerase alpha activities in bone marrow cells from patients with vitamin B12 deficient megaloblastic anemia

Blood ◽

10.1182/blood.v59.4.832.832 ◽

1982 ◽

Vol 59 (4) ◽

pp. 832-837 ◽

Cited By ~ 8

Author(s):

Y Kano ◽

S Sakamoto ◽

K Hida ◽

K Suda ◽

F Takaku

Keyword(s):

Bone Marrow ◽

Vitamin B12 ◽

Dna Polymerase ◽

Methylenetetrahydrofolate Reductase ◽

Bone Marrow Cells ◽

Megaloblastic Anemia ◽

Vitamin B12 Deficiency ◽

Dna Polymerase Alpha ◽

B12 Deficiency ◽

Marrow Cells

Abstract The activities of 5-methyltetrahydrofolate (5-CH3THF) related enzymes and DNA polymerase alpha were determined in bone marrow cells obtained from patients with vitamin B12 deficient megaloblastic anemia and compared with those from healthy volunteers and patients with hemolytic anemia. 5-CH3THF homocysteine methyltransferase activity was significantly lower than that in the control subjects. 5,10- methylenetetrahydrofolate reductase activity was only slightly elevated to that in the control subjects. DNA polymerase alpha activity was significantly higher than that in the control. High deoxyuridine suppression test values in vitamin B12 deficient bone marrow cells were improved by tetrahydrofolate, but not by 5-CH3THF. These data indicate that, even though the reverse reaction catalyzed by 5,10- methylenetetrahydrofolate reductase may be operative in vitamin B12 deficiency, it is not sufficient to correct the disturbance in folate metabolism in vitamin B12 deficiency. Increased DNA polymerase alpha activity may be due to compensation for disarranged DNA synthesis.

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Vitamin B12 Deficiency Resembling Acute Leukemia: A Case Report

Journal of Nepal Medical Association ◽

10.31729/jnma.6600 ◽

2021 ◽

Vol 59 (243) ◽

pp. 1182-1184

Author(s):

Nisha Sharma ◽

Saru Kunwar ◽

Anil Kumar Shrestha

Keyword(s):

Bone Marrow ◽

Acute Leukemia ◽

Vitamin B12 ◽

Megaloblastic Anemia ◽

Vitamin B12 Deficiency ◽

Bone Marrow Aspiration ◽

Peripheral Blood Smear ◽

Poor Growth ◽

B12 Deficiency ◽

Chronic Fever

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.

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Erythropoiesis during recovery from macrocytic anemia: macrocytes, normocytes, and microcytes

Blood ◽

10.1182/blood.v50.6.995.995 ◽

1977 ◽

Vol 50 (6) ◽

pp. 995-1000 ◽

Cited By ~ 6

Author(s):

D Bessman

Keyword(s):

Iron Deficiency ◽

Vitamin B12 ◽

Autoimmune Hemolytic Anemia ◽

Megaloblastic Anemia ◽

Macrocytic Anemia ◽

Vitamin B12 Deficiency ◽

Red Cells ◽

Red Cell ◽

Cell Size Distribution ◽

B12 Deficiency

Abstract In seven patients with marked megaloblastic anemia (MCV greater than 110 fl), red cell size distribution curves (erythrograms) demonstrated the size of red cells produced after therapy. In six, the new red cells were normocytic throughout recovery. In the seventh patient, folate repletion along produced a new population of microcytes, due to unsuspected iron deficiency; after iron repletion normocytes were produced. Three patients with autoimmune hemolytic anemia had macrocytosis (MCV greater than 110 fl) without folate or vitamin B12 deficiency. During recovery with predisone therapy, instead of a discrete new normocytic population appearing, the entire population progressively returned to normal size. Normal rather than “stress” reticulocytes, and remodeled stress reticulocytes remaining, may explain this different pattern of recovery. Two patients initially had minor subpopulations of smaller red cells that disappeared soon after therapy. These probably reflected the dyserythropoiesis of severe megaloblastic anemia.

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Erythropoiesis during recovery from macrocytic anemia: macrocytes, normocytes, and microcytes

Blood ◽

10.1182/blood.v50.6.995.bloodjournal506995 ◽

1977 ◽

Vol 50 (6) ◽

pp. 995-1000

Author(s):

D Bessman

Keyword(s):

Iron Deficiency ◽

Vitamin B12 ◽

Autoimmune Hemolytic Anemia ◽

Megaloblastic Anemia ◽

Macrocytic Anemia ◽

Vitamin B12 Deficiency ◽

Red Cells ◽

Red Cell ◽

Cell Size Distribution ◽

B12 Deficiency

In seven patients with marked megaloblastic anemia (MCV greater than 110 fl), red cell size distribution curves (erythrograms) demonstrated the size of red cells produced after therapy. In six, the new red cells were normocytic throughout recovery. In the seventh patient, folate repletion along produced a new population of microcytes, due to unsuspected iron deficiency; after iron repletion normocytes were produced. Three patients with autoimmune hemolytic anemia had macrocytosis (MCV greater than 110 fl) without folate or vitamin B12 deficiency. During recovery with predisone therapy, instead of a discrete new normocytic population appearing, the entire population progressively returned to normal size. Normal rather than “stress” reticulocytes, and remodeled stress reticulocytes remaining, may explain this different pattern of recovery. Two patients initially had minor subpopulations of smaller red cells that disappeared soon after therapy. These probably reflected the dyserythropoiesis of severe megaloblastic anemia.

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