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Clinical Laboratory Oct 2023Vitamin B12, or cobalamin deficiency, an infrequent clinical entity in pediatric age, is found almost solely in breastfed infants whose mothers are purely vegetarian,...
BACKGROUND
Vitamin B12, or cobalamin deficiency, an infrequent clinical entity in pediatric age, is found almost solely in breastfed infants whose mothers are purely vegetarian, non-supplemented or with pernicious anemia. Megaloblastic anemia in infants presents with generalized weakness or irritability.
METHODS
Diagnosis is usually centered on complete blood count, vitamin dosing, and peripheral smear, which may show macrocytes, hypersegmented neutrophils, reticulocytopenia and a raised mean corpuscular volume (MCV ˃ 100 fL). Pancytopenia has also been noted.
RESULTS
We report an exclusive breastfed nine-month-old female child who presented with irritability, developmental delay, and difficulties in introducing new foods. Her initial blood count revealed pancytopenia. Vitamin B12 levels were found to be reduced. Maternal levels of Vitamin B12 were also found to be borderline low. The child was treated as per protocols, and improvement was evidenced with the return of hematological parameters to the regular and gradual advancement of milestones.
CONCLUSIONS
We aim to underscore the importance of megaloblastic anemia as an important and rare cause of anemia in infancy.
Topics: Humans; Infant; Child; Female; Pancytopenia; Anemia, Megaloblastic; Vitamin B 12 Deficiency; Vitamin B 12; Anemia, Pernicious
PubMed: 37844051
DOI: 10.7754/Clin.Lab.2023.230420 -
Cureus Aug 2023Background and aims The prevalence of vitamin B12 deficiency is found to coexist in hypothyroid patients, causing the persistence of symptoms concomitant to both...
Background and aims The prevalence of vitamin B12 deficiency is found to coexist in hypothyroid patients, causing the persistence of symptoms concomitant to both diseases even on adequate thyroxine supplementation. Primary objective To study vitamin B12 levels in patients with hypothyroidism. Secondary objective To study the clinical profile of patients with hypothyroidism with special reference to anemia, and to study the association between vitamin B12 deficiency with anti-thyroid peroxidase (anti-TPO) antibodies and anti-thyroglobulin (anti-Tg) antibodies in patients with hypothyroidism. Methods and results A single-centric cross-sectional study was carried out over a period of one year. Among 100 hypothyroid patients, 68% were found to be vitamin B12 deficient, among whom 73.5% were females. Of patients with raised anti-TPO antibodies, 78.6% had vitamin B12 deficiency (p = 0.01), while 78% of patients with raised anti-Tg antibodies were vitamin B12 deficient (p = 0.07). The Pearson correlation coefficient (r) of vitamin B12 with anti-TPO and anti-Tg antibodies was -0.302 (p = 0.002) and -0.253 (p = 0.011), respectively. Conclusion There is a predilection of hypothyroid patients toward developing anemia, with vitamin B12 deficiency as a major etiology. This finding can be correlated with the hematopoietic action of thyroid-stimulating hormones as well as autoimmune thyroid disease predisposing to pernicious anemia.
PubMed: 37767262
DOI: 10.7759/cureus.44197 -
Frontiers in Immunology 2023Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked enzymatic disorder that is particularly prevalent in Africa, Asia, and the Middle East. This study... (Observational Study)
Observational Study
INTRODUCTION
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked enzymatic disorder that is particularly prevalent in Africa, Asia, and the Middle East. This study aimed to assess the long-term health risks associated with G6PD deficiency.
METHODS
A retrospective cohort study was conducted using data from a national healthcare provider in Israel (Leumit Health Services). A total of 7,473 G6PD-deficient individuals were matched with 29,892 control subjects in a 1:4 ratio, based on age, gender, socioeconomic status, and ethnic groups. The exposure of interest was recorded G6PD diagnosis or positive G6PD diagnostic test. The main outcomes and measures included rates of infectious diseases, allergic conditions, and autoimmune disorders between 2002 and 2022.
RESULTS
Significantly increased rates were observed for autoimmune disorders, infectious diseases, and allergic conditions in G6PD-deficient individuals compared to the control group. Specifically, notable increases were observed for rheumatoid arthritis (odds ratio [OR] 2.41, p<0.001), systemic lupus erythematosus (OR 4.56, p<0.001), scleroderma (OR 6.87, p<0.001), pernicious anemia (OR 18.70, p<0.001), fibromyalgia (OR 1.98, p<0.001), Graves' disease (OR 1.46, p=0.001), and Hashimoto's thyroiditis (OR 1.26, p=0.001). These findings were supported by elevated rates of positive autoimmune serology and higher utilization of medications commonly used to treat autoimmune conditions in the G6PD-deficient group.
DISCUSSION
In conclusion, individuals with G6PD deficiency are at a higher risk of developing autoimmune disorders, infectious diseases, and allergic conditions. This large-scale observational study provides valuable insights into the comprehensive association between G6PD deficiency and infectious and immune-related diseases. The findings emphasize the importance of considering G6PD deficiency as a potential risk factor in clinical practice and further research is warranted to better understand the underlying mechanisms of these associations.
Topics: Humans; Arthritis, Rheumatoid; Autoimmune Diseases; Glucosephosphate Dehydrogenase Deficiency; Graves Disease; Hypersensitivity; Retrospective Studies
PubMed: 37753082
DOI: 10.3389/fimmu.2023.1232560 -
BMC Medicine Sep 2023Some patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) go on to experience post-COVID-19 condition or long COVID. Preliminary findings...
BACKGROUND
Some patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) go on to experience post-COVID-19 condition or long COVID. Preliminary findings have given rise to the theory that long COVID may be due in part to a deranged immune response. In this study, we assess whether there is an association between SARS-CoV-2 infection and the incidence of immune-mediated inflammatory diseases (IMIDs).
METHODS
Matched cohort study using primary care electronic health record data from the Clinical Practice Research Datalink Aurum database. The exposed cohort included 458,147 adults aged 18 years and older with a confirmed SARS-CoV-2 infection and no prior diagnosis of IMIDs. They were matched on age, sex, and general practice to 1,818,929 adults with no diagnosis of confirmed or suspected SARS-CoV-2 infection. The primary outcome was a composite of any of the following IMIDs: autoimmune thyroiditis, coeliac disease, inflammatory bowel disease (IBD), myasthenia gravis, pernicious anaemia, psoriasis, rheumatoid arthritis (RA), Sjogren's syndrome, systemic lupus erythematosus (SLE), type 1 diabetes mellitus (T1DM), and vitiligo. The secondary outcomes were each of these conditions separately. Cox proportional hazard models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for the primary and secondary outcomes, adjusting for age, sex, ethnic group, smoking status, body mass index, relevant infections, and medications.
RESULTS
Six hundred and nighty six (0.15%) and 2230 (0.12%) patients in the exposed and unexposed cohort developed an IMID during the follow-up period over 0.29 person-years, giving a crude incidence rate of 4.59 and 3.65 per 1000 person-years, respectively. Patients in the exposed cohort had a 22% increased risk of developing an IMID, compared to the unexposed cohort (aHR 1.22, 95% CI 1.12 to 1.33). The incidence of three IMIDs was significantly associated with SARS-CoV-2 infection. These were T1DM (aHR 1.56, 1.09 to 2.23), IBD (aHR 1.36, 1.18 to 1.56), and psoriasis (1.23, 1.05 to 1.42).
CONCLUSIONS
SARS-CoV-2 was associated with an increased incidence of IMIDs including T1DM, IBD and psoriasis. However, these findings could be potentially due to ascertainment bias. Further research is needed to replicate these findings in other populations and to measure autoantibody profiles in cohorts of individuals with COVID-19.
Topics: Adult; Humans; COVID-19; SARS-CoV-2; Post-Acute COVID-19 Syndrome; Incidence; Cohort Studies; Diabetes Mellitus, Type 1; Immunomodulating Agents; Primary Health Care; United Kingdom
PubMed: 37735654
DOI: 10.1186/s12916-023-03049-5 -
Clinical Laboratory Sep 2023Thiamine responsive megaloblastic anemia (TRMA) is a genetic disease caused by SLC19A2 gene mutation. This study aimed to preliminarily explore the relationship between...
BACKGROUND
Thiamine responsive megaloblastic anemia (TRMA) is a genetic disease caused by SLC19A2 gene mutation. This study aimed to preliminarily explore the relationship between endoplasmic reticulum stress (ERS)-PERK signaling pathway and the pathogenesis of hyperglycemia induced by TRMA.
METHODS
Islet β (INS.1 and β-TC-6) and HEK293T cell line models with stable overexpression of SLC19A2 and SLC19A2 (c.1409insT) were established. The cells were divided into empty virus group (control), wild-type group (overexpressed SLC19A2), and mutation group (overexpressed SLC19A2 (c.1409insT)). Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and western blotting were used to detect the expression levels of ERS-PERK signaling pathway-related proteins, including glucose-regulated protein 78 (GRP78), protein kinase R-like ER kinase (PERK), and eukaryotic initiation factor 2 (eIF2α), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP) in islet β cells. Protein localization was assessed by immunofluorescence staining.
RESULTS
Compared with the control group, the mRNA expression levels of SLC19A2 in wild-type and mutant islet β cells (INS.1 and β-TC-6) and HEK293T cells were significantly upregulated (all p < 0.05). Compared with the control group and the wild-type group, the mRNA expression levels of GRP78, PERK, eIF2α, ATF4, and CHOP were increased (all p < 0.05) in the mutant islet β cells; the protein expression levels of PERK, GRP78, and eIF2α were elevated (all p < 0.05). In addition, the results of immunofluorescence staining showed that SLC19A2 (c.1409insT) mutation changed the localization of the proteins in the cells. Thus, they were not located on the cell surface, but in the cytoplasm and nuclei, and protein aggregation occurred in the cytoplasm.
CONCLUSIONS
1. Islet β and HEK293Tcell lines, stably overexpressing SLC19A2 and SLC19A2 (c.1409insT) mutations, were successfully constructed. 2. SLC19A2 (c.1409insT) mutation could raise the expression levels of ERS-PERK signaling pathway-related proteins (GRP78, PERK, eIF2α, ATF4, and CHOP), and activate apoptosis pathway. 3. SLC19A2 (c.1409insT) mutation could change the localization of proteins and produce protein aggregation in cells. It could lead to protein misfolding and ERS, which would participate in the pathological mechanism of hyperglycemia induced by TRMA.
Topics: Humans; Endoplasmic Reticulum Chaperone BiP; HEK293 Cells; Protein Aggregates; Hyperglycemia; Anemia, Pernicious; Endoplasmic Reticulum Stress; Thiamine; RNA, Messenger; Membrane Transport Proteins
PubMed: 37702666
DOI: 10.7754/Clin.Lab.2023.230324 -
Cureus Aug 2023Pernicious anemia (PA) is a chronic inflammatory destructive disease of parietal cells of predominantly the gastric fundus. It leads to vitamin B (cobalamin) deficiency...
Pernicious anemia (PA) is a chronic inflammatory destructive disease of parietal cells of predominantly the gastric fundus. It leads to vitamin B (cobalamin) deficiency secondary to a deficiency of intrinsic factors. Despite the medical advances nowadays, diagnosing PA can be challenging. This report highlights a neglected case of PA with ongoing subacute combined degeneration of the cord (SCDS) in an elderly patient. An 86-year-old lady with multiple comorbidities was referred to the hematology outpatient clinic for refractory anemia for the last two months. At first, her general practitioner (GP) treated her as a case of anemia of chronic disease but without improvement. Her initial clinical assessment revealed hematological and neurological manifestations of undetermined origin, including global weakness, hypertonia, and hyperreflexia with sensory deficits, especially in the lower limbs. On investigation, the hemoglobin level was 9 g/dL with high indirect bilirubinemia and lactate dehydrogenase (LDH). Despite the normal mean corpuscular volume (MCV) and peripheral blood smear, positive anti-intrinsic factor and parietal cell antibodies tests were subsequently reported, suggesting the diagnosis of PA. As a result, she was commenced on lifelong parenteral cobalamin replacement therapy. On follow-up visits of three months, she illustrated a clinical recovery in fatigability and paranesthesia. As expected, the laboratory parameters revealed a rise in hemoglobin level (11 g/dL) and serum vitamin B (418 pg/mL). However, she remained bedridden with spastic limbs. Clinicians should have a high index of suspicion since PA is a rare disease with variable clinical presentations. The optimal management approach is by a multidisciplinary care team of internists, neurologists, gastroenterologists, and hematologists.
PubMed: 37680425
DOI: 10.7759/cureus.43045 -
Clinical Chemistry Oct 2023Autoimmune atrophic gastritis (AAG) is a persistent, corpus-restricted immune-mediated destruction of the gastric corpus oxyntic mucosa with reduced gastric acid and... (Review)
Review
BACKGROUND
Autoimmune atrophic gastritis (AAG) is a persistent, corpus-restricted immune-mediated destruction of the gastric corpus oxyntic mucosa with reduced gastric acid and intrinsic factor secretion, leading to iron deficiency and pernicious anemia as a consequence of iron and cobalamin malabsorption. Positivity toward parietal cell (PCA) and intrinsic factor (IFA) autoantibodies is very common. AAG may remain asymptomatic for many years, thus making its diagnosis complex and often delayed. Due to the increased risk of gastric neoplasms, a timely diagnosis of AAG is clinically important.
CONTENT
The gold standard for AAG diagnosis is histopathological assessment of gastric biopsies obtained during gastroscopy, but noninvasive, preendoscopic serological screening may be useful in some clinical scenarios. Serum biomarkers for AAG may be divided into 2 groups: gastric autoimmunity-related biomarkers, such as PCA and IFA, and gastric corpus atrophy/reduced gastric acid secretion-related biomarkers, such as serum gastrin and pepsinogens. The present review focuses on the clinical significance and pitfalls of serum biomarkers related to gastric autoimmunity and gastric corpus atrophy, including some discussion of analytical methods.
SUMMARY
Serum assays for PCA, IFA, gastrin, and pepsinogen I show good diagnostic accuracy for noninvasive diagnostic work-up of AAG. Diagnostic performance may increase by combining >1 of these tests, overcoming the problem of seronegative AAG. However, appropriately designed, comparative studies with well-characterized patient cohorts are needed to better define the reliability of these biomarkers in the diagnosis of patients with AAG. Currently, positive serum tests should always be followed by the state-of-art diagnostic test, that is, histopathological assessment of gastric biopsies obtained during gastroscopy to definitively confirm or rule out AAG and eventually neoplastic complications.
Topics: Humans; Gastritis, Atrophic; Gastrins; Intrinsic Factor; Reproducibility of Results; Atrophy; Biomarkers; Helicobacter pylori
PubMed: 37680186
DOI: 10.1093/clinchem/hvad082 -
Cureus Aug 2023While macrocytic anemia is common in vitamin B12 deficiency, rarely, pancytopenia and hemolytic anemia can occur. Homocysteine levels are elevated in severe B12...
While macrocytic anemia is common in vitamin B12 deficiency, rarely, pancytopenia and hemolytic anemia can occur. Homocysteine levels are elevated in severe B12 deficiency, and this is linked to thrombus formation with potentially life-threatening complications. We present a patient with severe vitamin B12 deficiency complicated by hyperhomocysteinemia and obstructive shock from pulmonary embolism. A 56-year-old male with no medical history presented to the hospital with altered mentation. The patient's family stated he was experiencing bilateral paresthesias of his lower extremities, progressive depression, anxiety, and insomnia. Initial vitals were blood pressure of 76/36, heart rate of 70 beats per minute, respiratory rate of 14, and temperature of 36.3 degrees Celsius. He was intubated due to severe encephalopathy. Relevant labs indicated severe macrocytic anemia, thrombocytopenia, decreased B12 levels, elevated methylmalonic acid, and elevated homocysteine. Imaging demonstrated a right common femoral vein thrombosis and subsegmental pulmonary emboli. Peripheral blood smear revealed schistocytes, anisopoikilocytosis, and decreased platelet count. The patient required fluid resuscitation, antibiotics, and multiple blood products. Vitamin B12 was administered intramuscularly, which improved the anemia. Esophagogastroduodenoscopy (EGD) demonstrated gastritis. Gastric and duodenal biopsies were negative for and celiac disease. He was negative for intrinsic factor (IF) antibodies but had elevated gastrin levels. An intravenous unfractionated heparin infusion was started when the platelet count was above 50000. The patient was extubated after seven days. Heparin was transitioned to apixaban and an inferior vena cava (IVC) filter was placed. Hyperhomocysteinemia is a known pro-thrombotic factor that can lead to the development of venous thromboembolism. B12 malabsorption can stem from inflammatory bowel disease, celiac disease, gastritis, pancreatic insufficiency, gastrectomy, gastric bypass surgery, or antibodies to IF. While this case showed gastritis and negative IF antibodies, gastrin levels were elevated, indicating a mixed picture. This highlights the challenge of definitively diagnosing pernicious anemia as the cause of vitamin B12 deficiency. Vitamin B12 deficiency may lead to critical illness in which thromboembolism develops secondary to hyperhomocysteinemia.
PubMed: 37664295
DOI: 10.7759/cureus.42908 -
Case Reports in Immunology 2023Pernicious anemia is an autoimmune disease caused by the malabsorption of vitamin B12. It usually appears in the elderly. People with trisomy 21 are susceptible to...
Pernicious anemia is an autoimmune disease caused by the malabsorption of vitamin B12. It usually appears in the elderly. People with trisomy 21 are susceptible to autoimmune diseases. This susceptibility is thought to be due to altered expression of the gene, which is located in the 21q22.3 region. Although pernicious anemia is not common in people with trisomy 21, is pointed out as a susceptibility gene of pernicious anemia in a genome-wide association study. Here, we report a man with trisomy 21, who suffered from the pernicious anemia. When he was in his 30 s, he visited our hospital because of diarrhea and poor oral intake. He showed thrombocytopenic purpura-like features, and was diagnosed as pernicious anemia. After supplementation of vitamin B12, he recovered from the illness. The reason for his early onset may be because of trisomy 21. Altered expression of might trigger the disease.
PubMed: 37663274
DOI: 10.1155/2023/2747756 -
Gastroenterology Dec 2023
Topics: Humans; Stomach; Anemia; Upper Gastrointestinal Tract; Abdomen; Anemia, Pernicious; Stomach Neoplasms
PubMed: 37640254
DOI: 10.1053/j.gastro.2023.08.032