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The Pan African Medical Journal 2018A vitamin B12 deficiency in infants is rare, but may sometimes be seen in breastfed babies of strict vegetarian mothers. Vitamin B12, also known as cobalamin, is only...
A vitamin B12 deficiency in infants is rare, but may sometimes be seen in breastfed babies of strict vegetarian mothers. Vitamin B12, also known as cobalamin, is only found in meat and other animal products. Most babies have a sufficient supply as long as the mother was not deficient herself. Symptoms and signs of vitamin B12 deficiency appear between the ages of 2 to 12 months and include vomiting, lethargy, failure to thrive, hypotonia, and arrest or regression of developmental skills. Urinary concentrations of methylmalonic acid and homocystine are characteristically elevated in vitamin B12 deficiency. Early treatment for a vitamin B12 deficiency in an infant involves immediate administration of vitamin B12 to the baby and the breastfeeding mother. The infant and mother will each receive an injection of vitamin B12 containing 1,000 mcg or more of the vitamin, and the mother will continue to receive injections every month to raise her own stores. After the initial injection, the baby will often receive future vitamin B12 through food sources. We present a case of vitamin B12 deficiency in a 9-month-old girl presented with psychomotor regression, hypotonia and lethargy. The child was exclusively breast-fed from birth by a mother who was on strict vegetarian diet and belong to a low socio-economic status. Laboratory data revealed bicytopenia with macrocytic anemia and methylmalonic acid in the urine, consistent with vitamin B12 deficient anemia. The Brain CT revealed a cerebral atrophy and delayed myelination. Vitamin B12 supply was effective on anaemia and psychomotor delay. This case figures out the importance of an early diagnosis in front of psychomoteur regression and hypotonia, given the risk of incomplete neurologic recovery due to vitamin B12 deficiency mainly in the setting of maternal nutritional deficiency.
Topics: Anemia, Macrocytic; Breast Feeding; Female; Humans; Infant; Mothers; Muscle Hypotonia; Psychomotor Disorders; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency
PubMed: 30374398
DOI: 10.11604/pamj.2018.30.152.12046 -
American Journal of Hematology Jan 2000Thymomas are often associated with autoimmune disorders. We report on a 45-year-old female patient with thymoma and hypogammaglobulinemia (Good's syndrome) who developed...
Thymomas are often associated with autoimmune disorders. We report on a 45-year-old female patient with thymoma and hypogammaglobulinemia (Good's syndrome) who developed symptomatic macrocytic anemia (Hb 4.4 g/dl, MCV 112 fl) and thrombocytosis (Plt 442 G/l). Besides hypogammaglobulinemia (IgG 589 mg/dl), an inverted ratio of CD4(+)/CD8(+) cells was seen. The bone marrow biopsy showed a slightly hypercellular bone marrow with normal granulopoiesis, normal megakaryopoiesis and a mild dyserythropoiesis without any ring-sideroblasts. The in-vitro stem cell culture from the bone marrow revealed an atypical growth of macroclusters, reduced BFU-E and CFU-GEMM colony growth, whereas the CFU-GM colony growth was within the normal range. The chromosomal analysis showed a normal karyotype. The plasma vitamin B(12) and folate levels were within normal ranges, and we could not detect any autoantibodies. These findings excluded the differential diagnoses pure red cell aplasia (PRCA) and pernicious anemia. After resection of the thymoma of mixed cell type, the macrocytic anemia and thrombocytosis disappeared. The clinical course was complicated by a cerebral palsy and a life-threatening fungal septicemia after surgery. In the third year after thymectomy, hyporegenerative macrocytic anemia and thrombocytosis reappeared and an immunosuppressive treatment with prednisolone (1 mg/kg BW) was started. After initiation of the prednisolone therapy, reticulocyte counts increased and macrocytic anemia as well as thrombocytosis disappeared. The normalization of these laboratory parameters during glucocorticoid therapy suggests that in rare cases the constellation of macrocytic anemia, thrombocytosis and hypogammaglobulinemia may be due to an underlying immunologic mechanism.
Topics: Agammaglobulinemia; Anemia, Macrocytic; Bone Marrow Cells; Cells, Cultured; Erythrocyte Indices; Female; Hematopoietic Stem Cells; Hemoglobins; Humans; Immunosuppressive Agents; Karyotyping; Middle Aged; Platelet Count; Prednisolone; Reticulocyte Count; Thrombocytosis; Thymoma; Thymus Neoplasms
PubMed: 10602167
DOI: 10.1002/(sici)1096-8652(200001)63:1<38::aid-ajh9>3.0.co;2-9 -
Leukemia Jul 2021Recurrent loss-of-function mutations of BCL6 co-repressor (BCOR) gene are found in about 4% of AML patients with normal karyotype and are associated with DNMT3a...
Recurrent loss-of-function mutations of BCL6 co-repressor (BCOR) gene are found in about 4% of AML patients with normal karyotype and are associated with DNMT3a mutations and poor prognosis. Therefore, new anti-leukemia treatments and mouse models are needed for this combinatorial AML genotype. For this purpose, we first generated a Bcor knockout mouse model characterized by impaired erythroid development (macrocytosis and anemia) and enhanced thrombopoiesis, which are both features of myelodysplasia/myeloproliferative neoplasms. We then created and characterized double Bcor/Dnmt3a knockout mice. Interestingly, these animals developed a fully penetrant acute erythroid leukemia (AEL) characterized by leukocytosis secondary to the expansion of blasts expressing c-Kit+ and the erythroid marker Ter119, macrocytic anemia and progressive reduction of the thrombocytosis associated with loss of Bcor alone. Transcriptomic analysis of double knockout bone marrow progenitors revealed that aberrant erythroid skewing was induced by epigenetic changes affecting specific transcriptional factors (GATA1-2) and cell-cycle regulators (Mdm2, Tp53). These findings prompted us to investigate the efficacy of demethylating agents in AEL, with significant impact on progressive leukemic burden and mice overall survival. Information gained from our model expands the knowledge on the biology of AEL and may help designing new rational treatments for patients suffering from this high-risk leukemia.
Topics: Anemia, Macrocytic; Animals; Bone Marrow; Cell Cycle; DNA (Cytosine-5-)-Methyltransferases; DNA Methyltransferase 3A; Disease Models, Animal; Erythroid Cells; Leukemia, Erythroblastic, Acute; Mice; Mice, Knockout; Repressor Proteins; Transcriptome
PubMed: 33159179
DOI: 10.1038/s41375-020-01075-3 -
Scientific Reports Aug 2016Tribbles homolog 2 (Trib2) is a member of Tribbles protein pseudokinases and involves in apoptosis, autoimmunity, cancer, leukemia and erythropoiesis, however, the...
Tribbles homolog 2 (Trib2) is a member of Tribbles protein pseudokinases and involves in apoptosis, autoimmunity, cancer, leukemia and erythropoiesis, however, the physiological function of Trib2 in hematopoietic system remains to be elucidated. Here, we report that Trib2 knockout (KO) mice manifest macrocytic anemia and increase of T lymphocytes. Although Trib2 deficient RBCs have similar half-life as the control RBCs, Trib2 KO mice are highly vulnerable to oxidant-induced hemolysis. Endogenous Trib2 mRNA is expressed in early hematopoietic progenitors, erythroid precursors, and lymphoid lineages, but not in mature RBCs, myeloid progenitors and granulocytes. Consistently, flow cytometric analysis and in vitro colony forming assay revealed that deletion of Trib2 mainly affected erythroid lineage development, and had no effect on either granulocyte or megakaryocyte lineages in bone marrow. Furthermore, a genetic approach using double knockout of Trib2 and C/ebpα genes in mice suggested that Trib2 promotes erythropoiesis independent of C/ebpα proteins in vivo. Finally, ectopic expression of human Trib2 in zebrafish embryos resulted in increased expression of erythropoiesis-related genes and of hemoglobin. Taking all data together, our results suggest that Trib2 positively promotes early erythrocyte differentiation and is essential for tolerance to hemolysis.
Topics: Anemia, Macrocytic; Animals; Calcium-Calmodulin-Dependent Protein Kinases; Erythroid Precursor Cells; Erythropoiesis; Gene Expression Regulation; Hemolysis; Humans; Intracellular Signaling Peptides and Proteins; Mice; Mice, Knockout; Protein Serine-Threonine Kinases; Zebrafish
PubMed: 27550848
DOI: 10.1038/srep31444 -
The American Journal of Clinical... Jan 2007Historic reports on the treatment of pernicious anemia with folic acid suggest that high-level folic acid fortification delays the diagnosis of or exacerbates the...
BACKGROUND
Historic reports on the treatment of pernicious anemia with folic acid suggest that high-level folic acid fortification delays the diagnosis of or exacerbates the effects of vitamin B-12 deficiency, which affects many seniors. This idea is controversial, however, because observational data are few and inconclusive. Furthermore, experimental investigation is unethical.
OBJECTIVE
We examined the relations between serum folate and vitamin B-12 status relative to anemia, macrocytosis, and cognitive impairment (ie, Digit Symbol-Coding score < 34) in senior participants in the 1999-2002 US National Health and Nutrition Examination Survey.
DESIGN
The subjects had normal serum creatinine concentrations and reported no history of stroke, alcoholism, recent anemia therapy, or diseases of the liver, thyroid, or coronary arteries (n = 1459). We defined low vitamin B-12 status as a serum vitamin B-12 concentration < 148 pmol/L or a serum methylmalonic acid concentration > 210 nmol/L-the maximum of the reference range for serum vitamin B-12-replete participants with normal creatinine.
RESULTS
After control for demographic characteristics, cancer, smoking, alcohol intake, serum ferritin, and serum creatinine, low versus normal vitamin B-12 status was associated with anemia [odds ratio (OR): 2.7; 95% CI: 1.7, 4.2], macrocytosis (OR: 1.8; 95% CI: 1.01, 3.3), and cognitive impairment (OR: 2.5; 95% CI: 1.6, 3.8). In the group with a low vitamin B-12 status, serum folate > 59 nmol/L (80th percentile), as opposed to < or = 59 nmol/L, was associated with anemia (OR: 3.1; 95% CI: 1.5, 6.6) and cognitive impairment (OR: 2.6; 95% CI: 1.1, 6.1). In the normal vitamin B-12 group, ORs relating high versus normal serum folate to these outcomes were < 1.0 (P(interaction) < 0.05), but significantly < 1.0 only for cognitive impairment (0.4; 95% CI: 0.2, 0.9).
CONCLUSION
In seniors with low vitamin B-12 status, high serum folate was associated with anemia and cognitive impairment. When vitamin B-12 status was normal, however, high serum folate was associated with protection against cognitive impairment.
Topics: Aged; Aging; Anemia; Anemia, Macrocytic; Cognition Disorders; Confidence Intervals; Creatinine; Female; Folic Acid; Food, Fortified; Humans; Male; Nutrition Surveys; Nutritional Status; Odds Ratio; Vitamin B 12; Vitamin B 12 Deficiency
PubMed: 17209196
DOI: 10.1093/ajcn/85.1.193 -
Bulletin of the World Health... 1963The importance of deficiency of the folic acid group of compounds (folates) in the pathogenesis of nutritional anaemias is receiving increasing recognition. There is...
The importance of deficiency of the folic acid group of compounds (folates) in the pathogenesis of nutritional anaemias is receiving increasing recognition. There is evidence that the megaloblastic anaemias, due to either vitamin B(12) or folate deficiency, may be the cause of widespread morbidity in malnourished populations. It was therefore considered timely to review certain aspects of the role of folates in megaloblastic anaemia, with special reference to the dietary intake in relation to human requirements, and the recognition of folate deficiency in man.
Topics: Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Folic Acid; Folic Acid Deficiency; Humans; Male; Vitamin A Deficiency; Vitamin B 12; Vitamin B 12 Deficiency
PubMed: 13935207
DOI: No ID Found -
BMJ Case Reports Oct 2010Folate-deficiency anaemia occurs in about 4 per 100 000 people, although severe cases causing moderate pancytopenia are rarer. We present the case of a significant...
Folate-deficiency anaemia occurs in about 4 per 100 000 people, although severe cases causing moderate pancytopenia are rarer. We present the case of a significant folate deficiency in a 50-year-old alcoholic with a background of mild liver impairment and recurrent nasal and rectal bleeding. Her blood tests showed profound macrocytic anaemia with haemoglobin 2.6 g/dl, leucopoenia with white cell count 3.2 × 10(9)/litre and thrombocytopenia with platelets 17 × 10(9)/litre. Serum folate was 0.8 ng/ml (normal 2.5-13.5 ng/ml) confirming severe deficiency. Despite these life-threatening results, the patient was stable, alert and was keen to avoid admission. Medical management of the anaemia included slow transfusion of red cells and one unit of platelets in view of haemorrhagic symptoms, two injections of vitamin B12 while awaiting assays and oral folic acid. A rapid improvement in the leucopoenia and thrombocytopenia resulted and no additional complications were encountered.
Topics: Anemia, Macrocytic; Combined Modality Therapy; Epistaxis; Erythrocyte Transfusion; Female; Folic Acid; Folic Acid Deficiency; Gastrointestinal Hemorrhage; Humans; Leukopenia; Liver Diseases, Alcoholic; Middle Aged; Pancytopenia; Platelet Transfusion; Thrombocytopenia; Vitamin B 12
PubMed: 22791479
DOI: 10.1136/bcr.03.2010.2851 -
American Journal of Hematology Nov 2022We diagnosed a 13-month-old girl with severe neurological deficits and hyporegenerative macrocytic anemiawith Brown-Vialetto-Van Laere syndrome type 2 (BVVL 2), a rare...
We diagnosed a 13-month-old girl with severe neurological deficits and hyporegenerative macrocytic anemiawith Brown-Vialetto-Van Laere syndrome type 2 (BVVL 2), a rare disorder of the riboflavin transporter, caused by variants in the SLC52A2 gene. Bone marrow aspiration revealed hypoplastic erythropoiesis and vacuolization of myelocytes, proerythroblasts, and micromegakaryocytes. We suggest BVVL 2 as an important differential diagnosis in hyporegenerative macrocytic anemia as rapid diagnosis and initiation of therapy are crucial for the remedy of hematological and neurological impairment.
Topics: Anemia, Macrocytic; Bulbar Palsy, Progressive; Female; Hearing Loss, Sensorineural; Humans; Infant; Riboflavin
PubMed: 35441393
DOI: 10.1002/ajh.26573 -
BMJ (Clinical Research Ed.) Feb 1997
Review
Topics: Anemia, Macrocytic; Folic Acid Deficiency; Humans; Vitamin B 12 Deficiency
PubMed: 9040391
DOI: 10.1136/bmj.314.7078.430 -
Journal of Clinical Pathology Sep 1987Developments relating to cobalamin and folate are reviewed. Current work on the relations between these two coenzymes are discussed, particularly those that have emerged... (Review)
Review
Developments relating to cobalamin and folate are reviewed. Current work on the relations between these two coenzymes are discussed, particularly those that have emerged in studies using nitrous oxide, which inactivates cobalamin.
Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Folic Acid; Humans; Intestinal Absorption; Vitamin B 12
PubMed: 3312306
DOI: 10.1136/jcp.40.9.978