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International Journal of Clinical and... 2015The present study describes a case of an elderly patient that was hospitalized secondary to hypotension and delirium. Physical examination at admission revealed...
The present study describes a case of an elderly patient that was hospitalized secondary to hypotension and delirium. Physical examination at admission revealed bilateral positive Babinski's sign. Laboratory examination revealed severe anemia. Bone marrow examination showed megaloblastic changes of the granulocyte and erythroid series, as well as other dyshaematopoiesis. The conditions of the patient rapidly improved after vitamin B12 treatments. Because the clinical manifestations of megaloblastic anemia are complex, this disease is often misdiagnosed in the geriatric population. Bone marrow examinations can aid in the diagnosis of anemia, but the results from these tests cannot always differentiate the type of anemia. Clinical management of the disorder is reliant upon proper classification of the type of anemia. The prognosis of megaloblastic anemia is typically good and a simple regimen of folic acid and/or vitamin B12 is effective.
PubMed: 26770511
DOI: No ID Found -
Clinica Chimica Acta; International... May 2021Thiamine-responsive megaloblastic anemia (TRMA), caused by SLC19A2 loss-of-function variants, is characterized by the triad of megaloblastic anemia, progressive...
BACKGROUND AND AIMS
Thiamine-responsive megaloblastic anemia (TRMA), caused by SLC19A2 loss-of-function variants, is characterized by the triad of megaloblastic anemia, progressive sensorineural deafness, and non-type 1 diabetes mellitus. Here, we present the case of a Chinese infant with two novel variants segregating in compound heterozygous form in SLC19A2 and reviewed genotype-phenotype associations (GPAs) in patients with TRMA.
MATERIALS AND METHODS
Whole-exome sequencing was performed to establish a genetic diagnosis. The clinical manifestations and genetic variants were collected by performing a literature review. The bioinformatics software SIFT, PolyPhen2, and Mutation Taster was applied to predict variant effects and analyze GPAs.
RESULTS
Two novel variants segregating in compound heterozygous form in SLC19A2 (NM_006996.2: exon2:c.336_363del:p.W112fs; exon2:c.358G>T:p.G120X) was identified. Thiamine supplementation corrected anemia and diabetes mellitus but did not improve the hearing defect. In the literature, 183 patients with TRMA with 74 variants in SLC19A2 have been reported, with high incidence in the Middle East, South Asia, and the northern Mediterranean. Patients with biallelic premature termination codon variants presented with more severe phenotypes, and truncating sites on extracellular domains was a protective factor for the hemoglobin level at diagnosis.
CONCLUSION
Two novel compound heterozygous variants (NM_006996.2: exon2:c.336_363del:p.W112fs; exon2:c.358G>T:p.G120X) were identified, and GPAs in TRMA indicated the predictability of clinical manifestations.
Topics: Anemia, Megaloblastic; Asia; Diabetes Mellitus; Genetic Association Studies; Hearing Loss, Sensorineural; Humans; Infant; Membrane Transport Proteins; Thiamine; Thiamine Deficiency
PubMed: 33571483
DOI: 10.1016/j.cca.2021.01.025 -
Blood Jan 1948
Topics: Anemia, Megaloblastic; Humans
PubMed: 18920895
DOI: No ID Found -
Frontiers in Immunology 2022Pernicious anemia (PA) is a megaloblastic anemia consisting of hematological, gastric and immunological alterations. The immunopathogenesis of PA is sustained by both...
Pernicious anemia (PA) is a megaloblastic anemia consisting of hematological, gastric and immunological alterations. The immunopathogenesis of PA is sustained by both autoantibodies (e.g. intrinsic factor (IFA) antibodies and anti parietal cell (PCA) antibodies and autoreactive T cells specific for IFA and the parietal cell proton pump ATPase. Iron deficient anemia (IDA) is a microcytic anemia and represents the most common cause of anemia worldwide. Our work aimed to investigate serum levels of several interleukins (IL) of the IL-20 cytokine subfamily in patients with PA, with IDA and in healthy subjects (HC). We compared serum levels of IL-19, IL-20, IL-26, IL-28A and IL-29 in 43 patients with PA and autoimmune gastritis, in 20 patients with IDA and no autoimmune gastritis, and in 47 HC. Furthermore, we analyzed the IL-19 cytokine production by gastric lamina propria mononuclear cells (LPMC) in eight patients with PA and four HC. We found that patients with PA have significantly higher serum levels of IL-19 (163.68 ± 75.96 pg/ml) than patients with IDA (35.49 ± 40.97 pg/ml; p<0.001) and healthy subjects (55.68 ± 36.75 pg/ml; p<0.001). Gastric LPMC from all PA patients were able to produce significantly higher levels of IL-19 (420.67 ± 68.14 pg/ml) than HC (53.69 ± 10.92 pg/ml) (<0.01). Altogether, our results indicate that IL-19 serum levels are significantly increased in patients with PA but not with IDA and that IL-19 is produced in the stomach of PA patients. These data open a new perspective on PA pathogenesis and suggest that IL-19 may represent a novel important tool for the management of patients with PA.
Topics: Anemia; Anemia, Pernicious; Autoantibodies; Cytokines; Gastritis; Humans; Interleukins
PubMed: 35479078
DOI: 10.3389/fimmu.2022.887256 -
Journal of Laboratory Physicians Dec 2021Megaloblastic anemia is one of the common causes of anemia in India. Duodenal biopsies are routinely performed in the investigation of megaloblastic anemia. The present...
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 B and folate status of these patients. 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 B 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. 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 B deficiency including low levels was present in 48.38% and folate deficiency was seen in 4.3% cases; 34.48% cases had both vitamin B and folate deficiency. 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.
PubMed: 34975246
DOI: 10.1055/s-0041-1730817 -
The Journal of Nutrition Oct 2020Homocysteine (Hcy) is methylated by methionine synthase to form methionine with methyl-cobalamin as a cofactor. The reaction demethylates 5-methyltetrahydrofolate to... (Review)
Review
Homocysteine (Hcy) is methylated by methionine synthase to form methionine with methyl-cobalamin as a cofactor. The reaction demethylates 5-methyltetrahydrofolate to tetrahydrofolate, which is required for DNA and RNA synthesis. Deficiency of either of the cobalamin (Cbl) and/or folate cofactors results in elevated Hcy and megaloblastic anemia. Elevated Hcy is a sensitive biomarker of Cbl and/or folate status and more specific than serum vitamin assays. Elevated Hcy normalizes when the correct vitamin is given. Elevated Hcy is associated with alcohol use disorder and drugs that target folate or Cbl metabolism, and is a risk factor for thrombotic vascular disease. Elevated methionine and cystathionine are associated with liver disease. Elevated Hcy, cystathionine, and cysteine, but not methionine, are common in patients with chronic renal failure. Higher cysteine predicts obesity and future weight gain. Serum S-adenosylhomocysteine (AdoHcy) is elevated in Cbl deficiency and chronic renal failure. Drugs that require methylation for catabolism may deplete liver S-adenosylmethionine and raise AdoHcy and Hcy. Deficiency of Cbl or folate or perturbations of their metabolism cause major changes in sulfur amino acids.
Topics: Alcoholism; Amino Acids, Sulfur; Anemia, Megaloblastic; Biomarkers; Cardiovascular Diseases; Folic Acid; Folic Acid Deficiency; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Liver Diseases; Nutritional Status; Obesity; S-Adenosylhomocysteine; Vitamin B 12; Vitamin B 12 Deficiency
PubMed: 33000156
DOI: 10.1093/jn/nxaa118 -
Cureus Oct 2022Background Pancytopenia is more of a manifestation of a spectrum of underlying diseases affecting the bone marrow. Specific treatment relies solely on early diagnosis...
Background Pancytopenia is more of a manifestation of a spectrum of underlying diseases affecting the bone marrow. Specific treatment relies solely on early diagnosis and identification of the accurate etiology. We aimed to generate data on the clinical and etiological profiles of patients diagnosed with pancytopenia. Materials and methods Fifty patients more than 13 years of age with pancytopenia who reported to a tertiary care hospital were included in the study. Thorough clinical examination, hematological investigation, and bone marrow biopsies were performed, and relevant data were recorded and analyzed statistically. Results Pancytopenia was most common in the age group of 25-34 years, with a male preponderance. The most common presenting complaints were fatigue and fever, with pallor present in all patients, followed by splenomegaly and hepatomegaly in a few patients. Aplastic anemia is the most common cause of pancytopenia, followed by megaloblastic anemia and leukemia. Conclusion While fatigue and fever are the most usual symptoms of pancytopenia, clinical pallor, hepatomegaly, and splenomegaly may be evident. Among the several etiologies, aplastic anemia is one of the most common causes of pancytopenia.
PubMed: 36407228
DOI: 10.7759/cureus.30449 -
Colombia Medica (Cali, Colombia) 2023Megaloblastic anemias secondary to Vitamin B12 deficiency are a group of pathologies produced by defective nuclear DNA synthesis.
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%, <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.
Topics: Male; Humans; Middle Aged; Female; Flow Cytometry; Anemia, Megaloblastic; Vitamin B 12 Deficiency; Vitamin B 12
PubMed: 37649984
DOI: 10.25100/cm.v54i2.5494 -
Italian Journal of Pediatrics Nov 2023Individuals with thiamine-responsive megaloblastic anemia (TRMA) mainly manifest macrocytic anemia, sensorineural deafness, ocular complications, and nonautoimmune...
BACKGROUND
Individuals with thiamine-responsive megaloblastic anemia (TRMA) mainly manifest macrocytic anemia, sensorineural deafness, ocular complications, and nonautoimmune diabetes. Macrocytic anemia and diabetes may be responsive to high-dosage thiamine treatment, in contrast to sensorineural deafness. Little is known about the efficacy of thiamine treatment on ocular manifestations.
CASES PRESENTATION
Our objective is to report data from four Italian TRMA patients: in Cases 1, 2 and 3, the diagnosis of TRMA was made at 9, 14 and 27 months. In 3 out of 4 subjects, thiamine therapy allowed both normalization of hyperglycemia, with consequent insulin suspension, and macrocytic anemia. In all Cases, thiamine therapy did not resolve the clinical manifestation of deafness. In Cases 2 and 3, follow-up showed no blindness, unlike Case 4, in which treatment was started for megaloblastic anemia at age 7 but was increased to high doses only at age 25, when the genetic diagnosis of TRMA was performed.
CONCLUSIONS
Early institution of high-dose thiamine supplementation seems to prevent the development of retinal changes and optic atrophy in TRMA patients. The spectrum of clinical manifestations is broad, and it is important to describe known Cases to gain a better understanding of this rare disease.
Topics: Humans; Child; Adult; Diabetes Mellitus; Hearing Loss, Sensorineural; Thiamine; Anemia, Megaloblastic; Early Diagnosis; Deafness
PubMed: 38037112
DOI: 10.1186/s13052-023-01553-1 -
Clinical Case Reports Jun 2020The case of thiamine-responsive megaloblastic anemia (TRMA) presented here speculates the need early diagnosis, continuous monitoring, follow-up, and regulated treatment...
The case of thiamine-responsive megaloblastic anemia (TRMA) presented here speculates the need early diagnosis, continuous monitoring, follow-up, and regulated treatment plan for the patients. Complications and systemic manifestations are likely to enhance in otherwise circumstances.
PubMed: 32577249
DOI: 10.1002/ccr3.2791