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Journal of Medical Cases Nov 2022Pernicious anemia is an autoimmune disorder that is characterized by the presence of autoantibodies to intrinsic factor and parietal cells which results in the inability...
Pernicious anemia is an autoimmune disorder that is characterized by the presence of autoantibodies to intrinsic factor and parietal cells which results in the inability to absorb vitamin B12. It is the most common manifestation of vitamin B12 deficiency and accounts for 20-50% of cases. Disseminated intravascular coagulation (DIC) is a clinical condition that is a complication of another process which causes the activation of coagulation. A 63-year-old female with a history of hypothyroidism presented with a 1-month history of worsening fatigue, intermittent epigastric pain, nausea, vomiting, and diarrhea. Initial laboratory findings showed severe anemia and macrocytosis with a hemoglobin of 4.3 g/dL and a mean corpuscular volume (MCV) of 138 fL. There was also a significant elevation of the D-dimer, lactate dehydrogenase (LDH), and creatinine. She received three units of packed red blood cells (pRBCs) and fluid resuscitation. A vitamin B12 level was obtained which revealed a severe vitamin B12 deficiency (< 150 pg/mL). Additional workup showed seropositivity for anti-parietal cell antibodies and intrinsic factor blocking antibodies, and an esophagogastroduodenoscopy (EGD) biopsy yielded histologic findings consistent with autoimmune gastritis. She was treated acutely with daily intramuscular B12 injections with improvement in hematologic derangements and symptomatology. Arrested erythropoiesis can lead to apoptosis and the high proliferation of immature erythroblasts results in cells that are more susceptible to impaired deoxyribonucleic acid (DNA) synthesis and results in denatured DNA. Pernicious anemia manifesting as DIC has yet to be described in the literature. Here we describe an interesting case of pernicious anemia manifesting as early DIC resulting from arrest of erythropoiesis evidenced by the international society on thrombosis and hemostasis score of 5, diagnostic for DIC. Early recognition and treatment of this reversible etiology of DIC is essential to the improvement of patient outcomes.
PubMed: 36506758
DOI: 10.14740/jmc4020 -
Nutrients Nov 2022Variation in vitamin B levels has been associated with a range of diseases across the life-course, the causal nature of which remains elusive. We aimed to interrogate...
Variation in vitamin B levels has been associated with a range of diseases across the life-course, the causal nature of which remains elusive. We aimed to interrogate genetically predicted vitamin B status in relation to a plethora of clinical outcomes available in the UK Biobank. Genome-wide association study (GWAS) summary data obtained from a Danish and Icelandic cohort of 45,576 individuals were used to identify 8 genetic variants associated with vitamin B levels, serving as genetic instruments for vitamin B status in subsequent analyses. We conducted a Mendelian randomisation (MR)-phenome-wide association study (PheWAS) of vitamin B status with 945 distinct phenotypes in 439,738 individuals from the UK Biobank using these 8 genetic instruments to proxy alterations in vitamin B status. We used external GWAS summary statistics for replication of significant findings. Correction for multiple testing was taken into consideration using a 5% false discovery rate (FDR) threshold. MR analysis identified an association between higher genetically predicted vitamin B status and lower risk of vitamin B deficiency (including all B vitamin deficiencies), serving as a positive control outcome. We further identified associations between higher genetically predicted vitamin B status and a reduced risk of megaloblastic anaemia (OR = 0.35, 95% CI: 0.20-0.50) and pernicious anaemia (0.29, 0.19-0.45), which was supported in replication analyses. Our study highlights that higher genetically predicted vitamin B status is potentially protective of risk of vitamin B deficiency associated with pernicious anaemia diagnosis, and reduces risk of megaloblastic anaemia. The potential use of genetically predicted vitamin B status in disease diagnosis, progression and management remains to be investigated.
Topics: Humans; Anemia, Megaloblastic; Anemia, Pernicious; Genome-Wide Association Study; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins; Mendelian Randomization Analysis
PubMed: 36501061
DOI: 10.3390/nu14235031 -
Discovery Medicine 2022Pernicious anemia (PA) is an autoimmune disease characterized by cobalamin deficiency (CD) due to immune-mediated chronic atrophic gastritis (CAG). CD results from poor...
Pernicious anemia (PA) is an autoimmune disease characterized by cobalamin deficiency (CD) due to immune-mediated chronic atrophic gastritis (CAG). CD results from poor absorption of dietary cobalamin from the terminal ileum, triggered by positive intrinsic factor (IF) antibodies. It is the most common cause of CD worldwide. Despite advances in understanding biochemistry and pathogenesis of PA, its diagnosis can be extremely challenging as the disease may present with hematological as well as nonhematological manifestations and also because of unreliable serum cobalamin assays. Nonhematological manifestations may present in a patient with PA even in the absence of hematological findings. Herein, an overview of common and uncommon nonhematological manifestations of PA is discussed.
Topics: Humans; Anemia, Pernicious
PubMed: 36476278
DOI: No ID Found -
Frontiers in Genetics 2022Expanded tandem repeat DNAs are associated with various unusual chromosomal lesions, despiralizations, multi-branched inter-chromosomal associations, and fragile sites.... (Review)
Review
Expanded tandem repeat DNAs are associated with various unusual chromosomal lesions, despiralizations, multi-branched inter-chromosomal associations, and fragile sites. Fragile sites cytogenetically manifest as localized gaps or discontinuities in chromosome structure and are an important genetic, biological, and health-related phenomena. Common fragile sites (∼230), present in most individuals, are induced by aphidicolin and can be associated with cancer; of the 27 molecularly-mapped common sites, none are associated with a particular DNA sequence motif. Rare fragile sites ( 40 known), 5% of the population (may be as few as a single individual), can be associated with neurodevelopmental disease. All 10 molecularly-mapped folate-sensitive fragile sites, the largest category of rare fragile sites, are caused by gene-specific CGG/CCG tandem repeat expansions that are aberrantly CpG methylated and include FRAXA, FRAXE, FRAXF, FRA2A, FRA7A, FRA10A, FRA11A, FRA11B, FRA12A, and FRA16A. The minisatellite-associated rare fragile sites, FRA10B, FRA16B, can be induced by AT-rich DNA-ligands or nucleotide analogs. Despiralized lesions and multi-branched inter-chromosomal associations at the heterochromatic satellite repeats of chromosomes 1, 9, 16 are inducible by de-methylating agents like 5-azadeoxycytidine and can spontaneously arise in patients with ICF syndrome (mmunodeficiency entromeric instability and acial anomalies) with mutations in genes regulating DNA methylation. ICF individuals have hypomethylated satellites I-III, alpha-satellites, and subtelomeric repeats. Ribosomal repeats and subtelomeric D4Z4 megasatellites/macrosatellites, are associated with chromosome location, fragility, and disease. Telomere repeats can also assume fragile sites. Dietary deficiencies of folate or vitamin B12, or drug insults are associated with megaloblastic and/or pernicious anemia, that display chromosomes with fragile sites. The recent discovery of many new tandem repeat expansion loci, with varied repeat motifs, where motif lengths can range from mono-nucleotides to megabase units, could be the molecular cause of new fragile sites, or other chromosomal lesions. This review focuses on repeat-associated fragility, covering their induction, cytogenetics, epigenetics, cell type specificity, genetic instability (repeat instability, micronuclei, deletions/rearrangements, and sister chromatid exchange), unusual heritability, disease association, and penetrance. Understanding tandem repeat-associated chromosomal fragile sites provides insight to chromosome structure, genome packaging, genetic instability, and disease.
PubMed: 36468036
DOI: 10.3389/fgene.2022.985975 -
Cureus Oct 2022Type 1 diabetes mellitus (T1DM) and multiple sclerosis (MS) have been described as chronic organ-specific diseases, approached by different medical specialties. However,...
Type 1 diabetes mellitus (T1DM) and multiple sclerosis (MS) have been described as chronic organ-specific diseases, approached by different medical specialties. However, they share more etiologic and pathologic features than expected between two autoimmune diseases. The authors present the case of a 40-year-old Caucasian male, diagnosed with type 1 diabetes mellitus at age 18, with poor metabolic control in the early years after the diagnosis. Fourteen years after the diagnosis of diabetes, he started complaining of paresthesias in both feet and sexual dysfunction. Months later, he began to have episodes of muscle weakness and decreased strength in the right lower limb, with a relapsing-remitting pattern and diplopia. This typical course of the symptoms associated with characteristic findings in brain magnetic resonance imaging, with multiple lesions, with evidence of space and time dissemination, established the diagnosis of multiple sclerosis. The presence of oligoclonal bands in the cerebrospinal fluid analysis sustained this diagnosis. Other alternative etiologies were excluded. People with type 1 diabetes mellitus are at an increased risk for other autoimmune diseases, with autoimmune thyroiditis (AIT), celiac disease, and pernicious anemia being the most common. Other less recognized associations, such as the co-occurrence of type 1 diabetes mellitus and multiple sclerosis, are also more frequent than might be thought, with studies reporting a threefold to fivefold higher prevalence of T1D in patients with MS. The exact mechanism behind this co-occurrence is not fully understood, but environmental factors (viral infections and vitamin D deficiency) and variations in non-human leucocyte antigen (HLA) class II alleles may be implicated. Understanding the similarities in the etiology and pathophysiology of these diseases may help clarify causality and create new strategies for the management of these conditions.
PubMed: 36447698
DOI: 10.7759/cureus.30762 -
Journal of Nutritional Science and... 2022Vitamins are a family of micronutrients comprising 13 groups of organic compounds, of which vitamin B1 was identified first, approximately 110 y ago. Deficiency of each... (Review)
Review
Vitamins are a family of micronutrients comprising 13 groups of organic compounds, of which vitamin B1 was identified first, approximately 110 y ago. Deficiency of each vitamin results in specific symptoms, such as neuropathy, dermatitis, diarrhea, dementia, pernicious anemia, scurvy, blindness, rickets, and bleeding. Almost all vitamins can modulate the functions of enzymes and/or other proteins involved in the formation of bone and soft tissues, generation of energy, and regulation of homeostasis via specific vitamin-protein interactions. In addition to the well-known physiological roles of vitamins, novel modes of action of vitamins have been elucidated. These new functions could contribute to extending healthy life expectancy by preventing and curing lifestyle-related diseases. In this mini-review, we introduce the functional properties of three vitamins, vitamin B3 (niacin), biotin, and vitamin K, for the prevention of age-related diseases.
Topics: Vitamins; Vitamin A; Vitamin K; Thiamine; Life Style
PubMed: 36437027
DOI: 10.3177/jnsv.68.S8 -
Federal Practitioner : For the Health... Jul 2022Pancytopenia is a result of increased destruction or decreased production of bone marrow cells and has a broad differential. Pernicious anemia commonly presents as a...
BACKGROUND
Pancytopenia is a result of increased destruction or decreased production of bone marrow cells and has a broad differential. Pernicious anemia commonly presents as a macrocytic anemia and is typically autoimmune in nature and the result of vitamin B deficiency. Pancytopenia is a rare presentation of this disorder especially in the setting of hemolysis. Testing in the deployed setting may be limited and/or challenging.
CASE PRESENTATION
A 24-year-old female patient with a history of Hashimoto thyroiditis presented during an overseas deployment with a witnessed syncopal episode and was found to be pancytopenic with a mild transaminitis and laboratory tests demonstrating hemolysis. Though initially she was hypotensive, tachycardic, and febrile, her vitals improved after multiple transfusions, but she had persistent cytopenia with transfusion dependence, concerning for aplastic anemia or acute leukemia.
CONCLUSIONS
Testing for B deficiency is crucial in symptomatic, patients with pancytopenic to either diagnose or exclude pernicious anemia and conserve resources by preventing costly workup and transfer/escalation of medical care, especially in the deployed setting. A predeployment screening in those with history of autoimmune disorders may be warranted.
PubMed: 36425352
DOI: 10.12788/fp.0320 -
Journal of Dental Sciences Oct 2022
PubMed: 36299305
DOI: 10.1016/j.jds.2022.09.006 -
Nutrients Sep 2022Gastric Intrinsic Factor (IF) is produced by the parietal cells of the stomach and secreted into the gastrointestinal tract where it ensures the active absorption of...
Gastric Intrinsic Factor (IF) is produced by the parietal cells of the stomach and secreted into the gastrointestinal tract where it ensures the active absorption of vitamin B12. We hypothesized that a small amount of IF ends up in the circulation and can be measured in serum. The aim of this study was to develop an assay for measuring human IF and to demonstrate its presence in serum. We designed a sensitive ELISA for measurement of human IF using a commercial monoclonal antibody and an in-house polyclonal antibody as capture and detecting antibody, respectively. Imprecision, accuracy, and linearity of the assay were examined. We established a reference interval based on serum samples from 240 healthy donors, and explored the daily IF fluctuations in 20 healthy subjects. Employing a prototype IF ELISA and size exclusion chromatography experiments, we demonstrated the presence of IF in human serum. In its final design, the IF ELISA has a measurement range of 0.2 to 50 pmol/L. The intra-assay and total imprecision were 7.9% and 15%, respectively. The 95% reference interval (18-65 years) was 1.7-11.6 pmol/L. No diurnal fluctuation or notable sex differences were observed. Our results suggest that the assay is capable of detecting and quantifying human IF in the circulation and may prove useful in the characterization of patients with impaired IF production.
Topics: Antibodies, Monoclonal; Enzyme-Linked Immunosorbent Assay; Female; Humans; Intrinsic Factor; Male; Reference Values; Vitamin B 12
PubMed: 36235695
DOI: 10.3390/nu14194043 -
The British Journal of General Practice... Dec 2022Individuals with vitamin B12 deficiency (including pernicious anaemia) often report being 'let down' or stigmatised by general practice systems and policy, and choose...
BACKGROUND
Individuals with vitamin B12 deficiency (including pernicious anaemia) often report being 'let down' or stigmatised by general practice systems and policy, and choose instead to self-medicate via injection; the association between this and perceptions of safe primary care in this group of people is unknown.
AIM
To examine the association between self-medication for vitamin B12 deficiency and patient-reported safety in primary care.
DESIGN AND SETTING
A UK cross-sectional online survey.
METHOD
The survey consisted of the three components: demographics; the validated Primary Care Patient Measure of Safety; and questions about self-medication for vitamin B12 deficiency. Multivariable logistic regression analyses and thematic synthesis were undertaken.
RESULTS
Responses from 1297 participants indicated 508 (39.2%) self-medicated via injection. Perceived primary care safety was low. Those who self-medicated via injection reported a significantly lower level of patient safety in primary care including adverse patient-related factors (odds ratio 0.82, 95% confidence interval = 0.73 to 0.92), and patients >34 years of age were significantly more likely to self-medicate via injection. Many reported that treatment under the guidance of a clinician was preferable to self-medication, but felt they had no other choice to regain quality of life. Almost half felt that the doctor did not always consider what they wanted for their care.
CONCLUSION
To the authors' knowledge, this is the largest study to date examining patient safety and vitamin B12 deficiency. It found that four out of 10 patients with B12 deficiency self-medicate via injection. Patients who self-medicated perceived primary care as less safe. Providing patient-centred care and treating these patients with dignity and respect is a policy priority to reduce unsafe health behaviours.
Topics: Humans; Vitamin B 12; Cross-Sectional Studies; Quality of Life; Patient Safety; Vitamin B 12 Deficiency; United Kingdom
PubMed: 36192360
DOI: 10.3399/BJGP.2021.0711