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Background: Vitamin B12 is an important micronutrient and its deficiency has been associated with various health issues like mild fatigue to severe neurological impairment and macrovascular diseases like coronary artery disease. Aim: The main aim was to find the correlation between vitamin B12 and lipid profile levels in patients attending Chirayu Hospital, Madhya Pradesh. Materials and Methods: This is a retrospective observational study done by including the lab records of patients who attended Chirayu Hospital and got their lipid profile and vitamin B12 levels done between January to June, 2023. After considering inclusion and exclusion criteria, the remaining subject's data was considered for the study. Vitamin B12 was estimated by CLIA method on Maglumi 2000 and lipid profile was estimated on Vitros 4600 equipment. Data was analyzed using appropriate statistical methods. Results: A total of 171 subjects aged between 18 to 89 years were included in the study. Out of total 171 subjects, 87 were males and 84 were females. The percentage of vitamin B12 deficiency among the subjects included in this study was 1.5%. There was no significant correlation between vitamin B12 and lipid profile levels (p>0.05). Conclusion: Early detection and treatment of dyslipidemia and vitamin B12 deficiency may help in preventing vascular and neurological complications. The results of this study suggest that there is no correlation between vitamin B12 deficiency and dyslipidemia. [ABSTRACT FROM AUTHOR]

Background: Nutritional deficiencies are the most common cause of anemia in the tropical countries. Deficiencies of vitamin B12 and folate can cause severe anemia and cytopenias due to ineffective hematopoiesis and can sometimes minor hemolytic anemia. Vitamin D deficiency is likely to play an important role in the very high prevalence of rickets, osteoporosis, cardiovascular diseases, diabetes, cancer and infections such as tuberculosis in India. Aim is to study Vitamin B12 and Vitamin D levels in factory employees. Objective is to evaluate Vitamin D and Vitamin B12 levels in factory employees and identify groups vulnerable for these deficiencies. Materials and Methods: Present cross-sectional study was performed in 714 factory employees from Chhatrapati Sambhaji Nagar district of Maharashtra for a period of 2 months. Vitamin D3 and vitamin B12 levels were estimated on Vitross 5600 dry chemistry with immunochemistry by Chemiluminescent Immunoassay platform from plain vacutainer samples. Statical analysis done by using Unpaired t Test. All the patients were in the fasting state. Results: 714 employees were examined for vitamin D and B12. Out of which 676 were males and 38 were females. Age range of employees were from 20 to 60 years. Out of which 18% males had deficiency, 73% males had insufficiency and only 9% males had sufficient levels of Vitamin D in males. For Vitamin B12 67.45% males had deficiency and 33% males had sufficient levels. For females: 37% females had deficiency, 53% had insufficiency and 11% had sufficient levels of Vitamin D3.42.1% females had deficiency and 58% females had sufficient levels of Vitamin B12. [ABSTRACT FROM AUTHOR]

Methylmalonic acid (MMA) is a byproduct of propionate metabolism linked to vitamin B12 deficiency. MMA alters cellular metabolism through direct regulation of metabolic enzymes. MMA activates succinate receptor 1 and drives inflammation. MMA acts as a signaling molecule through methylmalonylation of proteins. MMA is linked to the development of several age-related chronic disorders. Metabolic byproducts have conventionally been disregarded as waste products without functions. In this opinion article, we bring to light the multifaceted role of methylmalonic acid (MMA), a byproduct of the propionate metabolism pathway mostly commonly known as a clinical biomarker of vitamin B12 deficiency. MMA is normally present at low levels in the body, but increased levels can come from different sources, such as vitamin B12 deficiency, genetic mutations in enzymes related to the propionate pathway, the gut microbiota, and aggressive cancers. Here, we describe the diverse metabolic and signaling functions of MMA and discuss the consequences of increased MMA levels, such as during the aging process, for several age-related human pathologies. [ABSTRACT FROM AUTHOR]

Narcolepsy, a chronic neurologic sleep disorder, has sparked growing interest in the potential role of vitamin B12 in its pathogenic mechanism. However, research on this association has predominantly focused on adults. Our objective was to delineate the phenotypic and genetic connections between serum vitamin B12 levels and paediatric narcolepsy. To investigate the causal relationship between vitamin B12 and paediatric narcolepsy, we conducted a retrospective analysis involving 60 narcolepsy patients and a matched control group. Univariate and multivariate logistic regression models were employed to identify independent factors influencing paediatric narcolepsy. Furthermore, a bidirectional two-sample Mendelian randomization (MR) analysis was performed to assess the causal connection between serum vitamin B12 levels and narcolepsy. Paediatric narcolepsy patients showed significantly lower serum levels of vitamin B12 and folate compared to the control group (P < 0.05). Multivariate logistic regression analysis identified serum vitamin B12 as the exclusive independent factor influencing paediatric narcolepsy (P < 0.001; OR = 0.96; 95%CI: 0.94–0.98). Additionally, IVW model results provided compelling evidence supporting a potential causal association between serum vitamin B12 levels and paediatric narcolepsy (OR: 0.958, 95% CI = 0.946–0.969, P = 0.001). This study establishes connections at both phenotypic and genetic levels, associating vitamin B12 deficiency with an increased risk of paediatric narcolepsy. These findings provide innovative perspectives for clinical strategies in the prevention and treatment of narcolepsy. • Acknowledging the inherent limitations of observational studies, establishing a definitive causal or reverse causal association between vitamin B12 and narcolepsy proves challenging. • Serum vitamin B12 as the exclusive independent factor influencing paediatric narcolepsy. • Based on the MR findings, potential evidence was identified for the association between vitamin B12 deficiency and an increased risk of narcolepsy. [ABSTRACT FROM AUTHOR]

Introduction: Iron and vitamin B12 deficiencies are common in patients with atrophic gastritis, but there are limited data on the prevalence of these deficiencies in different types of atrophic gastritis. Methods: This multicenter, prospective study assessed micronutrient concentrations in histologically confirmed autoimmune gastritis (AIG, n = 45), Helicobacter pylori-related non-autoimmune gastritis (NAIG, n = 109), and control patients (n = 201). A multivariate analysis was performed to determine factors influencing those deficiencies. Results: The median vitamin B12 concentration was significantly lower in AIG (367.5 pg/mL, Q1, Q3: 235.5, 524.5) than in NAIG (445.0 pg/mL, Q1, Q3: 355.0, 565.0, p = 0.001) and control patients (391.0 pg/mL, Q1, Q3: 323.5, 488.7, p = 0.001). Vitamin B12 deficiency was found in 13.3%, 1.5%, and 2.8% of AIG, NAIG, and control patients, respectively. Similarly, the median ferritin concentration was significantly lower in AIG (39.5 ng/mL, Q1, Q3: 15.4, 98.3 ng/mL) than in NAIG (80.5 ng/mL, Q1, Q3: 43.6, 133.9, p = 0.04) and control patients (66.5 ng/mL, Q1, Q3: 33.4, 119.8, p = 0.007). Iron deficiency and iron deficiency adjusted to CRP were present in 28.9% and 33.3% of AIG, 12.8% and 16.5% of NAIG, and 12.9% and 18.4% of controls, respectively. Multivariate analysis demonstrated that AIG patients had a higher risk of developing vitamin B12 deficiency (OR: 11.52 [2.85–57.64, p = 0.001]) and iron deficiency (OR: 2.92 [1.32–6.30, p = 0.007]) compared to control patients. Factors like age, sex, and H. pylori status did not affect the occurrence of vitamin B12 or iron deficiency. Conclusion: Iron and vitamin B12 deficiencies are more commonly observed in patients with AIG than in those with NAIG or control patients. Therefore, it is essential to screen for both iron and vitamin B12 deficiencies in AIG patients and include the treatment of micronutrient deficiencies in the management of atrophic gastritis patients. [ABSTRACT FROM AUTHOR]

Background Use of nitrous oxide (N2O) gas for recreational purposes by young people is increasingly recognized as a public health hazard in the UK. Methods We looked at the hospital records of patients admitted over the last 4 years to a single neurological centre in Essex to determine the demographics, presentation, and management of patients presenting with symptoms of N2O toxicity from its recreational use. Results Of the 17 patients (mean age = 22.9 ± 3 years) admitted between September 2018 and October 2022, 70% were admitted between January and October 2022. All patients reported limb paraesthesiae and 16/17 reported (95%) imbalance; 11/17 (65%) showed objective limb weakness. Serum B12 concentration was low in 9/17 (53%). Plasma methylmalonic acid (n  = 7) and homocysteine (n  = 8) levels were elevated in all patients tested. Spinal cord Magnetic Resonance Imaging (MRI) imaging was abnormal in 10/17 (59%) patients. Nerve conduction studies were abnormal in 10/13 (77%) patients, with evidence of a symmetric, length-dependent, large fibre neuropathy. Conclusions There has been a recent surge of cases with neurological complications of recreational N2O abuse in the UK, with a relatively greater rate in 2022. Greater awareness of this condition amongst clinicians and health regulators is urgently required to prevent harm from N2O misuse in young people. Key messages: What is already known on this topic Nitrous oxide (N2O) used for recreational purposes causes a functional deficiency of vitamin B12, which can cause serious neurological problems, such as myelopathy and/or neuropathy, with significant disability What this study adds This study confirms that there has been a recent surge in the reported cases of N2O toxicity from recreational use by young people, and based on its public health impact, the UK government has recently enacted a legislation to make the use of N2O for recreation purposes illegal. How this study might affect research, practice, or policy There is a need for local and national guidance on the recognition and management of N2O toxicity. Timely detection and appropriate management in acute medical units are necessary to prevent serious harm. Prolonged clinical surveillance of these patients after discharge from hospital to obtain follow-up data regarding long-term outcomes is imperative. [ABSTRACT FROM AUTHOR]

Background/Aim: This study examines patients diagnosed with vitamin B12 deficiency in our department. Although rare, vitamin B12 deficiency is one of the causes of megaloblastic anemia, which can lead to negative outcomes in patients. We aim to promote earlier diagnosis to protect patients from these negative effects. Therefore, this study will contribute to raising awareness in the literature. Methods: Retrospectively, we included a total of 127 outpatient children, aged 0-18 years (0-215 months), who were diagnosed and treated for vitamin B12 deficiency at the Bagcilar Training and Research Hospital Child Health and Disease Clinic between October 2014 and February 2015. Results: Among the patients, 67 (53%) with vitamin B12 deficiency were female, while 60 (47%) were male, indicating a higher occurrence in girls. Vitamin B12 deficiency was most commonly observed in the age groups of 0-2 years and 12-17 years (adolescents). The mean vitamin B12 level was 168.1 (34.1) pg/mL, the mean hemoglobin level was 12 (1.9) g/dL, and the mean MCV (mean corpuscular volume) was 78.4 (8.1) fl. Anemia was observed in 38% of the patients, bicytopenia in 4%, neutropenia in 6%, thrombocytopenia in 9%, pancytopenia in 3%, and macrocytosis in 2%. Non-iron-deficient patients showed no difference in mean hemoglobin and RDW (red cell distribution width) when compared to irondeficient patients. However, their B12 levels were lower. The prevalence of iron deficiency did not differ between girls and boys. Comparing patients with vitamin B12 levels lower than 150 pg/mL to those with higher levels, there were no significant differences in average Hb, MCV, and RDW. Conclusion: It should be noted that macrocytic anemia is not exclusive to vitamin B12 deficiency. Vitamin B12 deficiency can manifest as normocytic anemia and should not be overlooked in biochemical assessments. It is recommended to conduct nationwide and regional prevalence studies to evaluate vitamin B12 deficiency as a public health issue and to develop new solutions accordingly. [ABSTRACT FROM AUTHOR]

Diabetic peripheral neuropathy occurs in up to 50% of patients with diabetes mellitus and increases the risk of diabetic foot ulcers and infections. Consistent screening and clear communication are essential to decrease disparities in assessment of neuropathic symptoms and diagnosis. Physicians should address underlying risk factors such as poor glycemic control, vitamin B12 deficiency, elevated blood pressure, and obesity to reduce the likelihood of developing neuropathy. First-line drug therapy for painful diabetic peripheral neuropathy includes duloxetine, gabapentin, amitriptyline, and pregabalin; however, these medications do not restore sensation to affected extremities. Evidence for long-term benefit and safety of first-line treatment options is lacking. Second-line drug therapy includes nortriptyline, imipramine, venlafaxine, carbamazepine, oxcarbazepine, topical lidocaine, and topical capsaicin. Periodic, objective monitoring of medication response is critical because patients may not obtain desired pain reduction, adverse effects are common, and serious adverse effects can occur. Opioids should generally be avoided. Nondrug therapies with low- to moderate-quality evidence include exercise and neuromodulation with spinal cord stimulation or transcutaneous electrical nerve stimulation. Peripheral transcutaneous electrical nerve stimulation is well tolerated and inexpensive, but benefits are modest. Other treatments, such as acupuncture, alpha-lipoic acid, acetyl-L-carnitine, cannabidiol, and onabotulinumtoxinA need further study in patients with diabetic peripheral neuropathy. (Am Fam Physician. 2024; 109(3):226–232. Copyright © 2024 American Academy of Family Physicians.) Diabetic peripheral neuropathy occurs in up to 50% of patients with diabetes mellitus and increases the risk of diabetic foot ulcers and infections. Consistent screening and clear communication are essential to decrease disparities in assessment of neuropathic symptoms and diagnosis. Physicians should address underlying risk factors such as poor glycemic control, vitamin B12 deficiency, elevated blood pressure, and obesity to reduce the likelihood of developing neuropathy. First-line drug therapy for painful diabetic peripheral neuropathy includes duloxetine, gabapentin, amitriptyline, and pregabalin; however, these medications do not restore sensation to affected extremities. Evidence for long-term benefit and safety of first-line treatment options is lacking. Second-line drug therapy includes nortriptyline, imipramine, venlafaxine, carbamazepine, oxcarbazepine, topical lidocaine, and topical capsaicin. Periodic, objective monitoring of medication response is critical because patients may not obtain desired pain reduction, adverse effects are common, and serious adverse effects can occur. Opioids should generally be avoided. Nondrug therapies with low- to moderate-quality evidence include exercise and neuromodulation with spinal cord stimulation or transcutaneous electrical nerve stimulation. Peripheral transcutaneous electrical nerve stimulation is well tolerated and inexpensive, but benefits are modest. Other treatments, such as acupuncture, alpha-lipoic acid, acetyl-L-carnitine, cannabidiol, and onabotulinumtoxinA need further study in patients with diabetic peripheral neuropathy. [ABSTRACT FROM AUTHOR]

Acylcarnitine and amino acid analyses of dried blood spot (DBS) samples using tandem mass spectrometry in newborn screening (NBS) programmes can generate false positive (FP) results. Therefore, implementation of second-tier tests (2TTs) using DBS samples has become increasingly important to avoid FPs. The most widely used 2TT metabolites include methylmalonic acid, 3-hydroxypropionic acid, methylcitric acid, and homocysteine. We simultaneously measured 46 underivatised metabolites, including organic acids, acylglycine and acylcarnitine isomers, homocysteine, and orotic acid, in DBS samples using tandem mass spectrometry. To validate this method, we analysed samples from 147 healthy newborns, 160 patients with genetic disorders diagnosed via NBS, 20 patients with acquired vitamin B12 deficiency, 10 newborns receiving antibiotic treatment, and nine external quality control samples. The validation study revealed that 31 metabolites showed good analytical performance. Furthermore, this method detected key metabolites for all diseases associated with increased levels of the following acylcarnitines: C3, C4, C5, C4DC/C5OH, and C5DC. The sensitivity of this method to detect all diseases was 100 %, and the specificity was 74–99 %, except for glutaric aciduria type 1. This method can also be used to diagnose mitochondrial fatty acid β-oxidation disorders (FAODs) and urea cycle defects (UCDs). We have described a 2TT panel of 31 metabolites in DBS samples based on an easy and rapid method without derivatisation. Its implementation allowed us to distinguish between different organic acidurias, some FAODs, and UCDs. This new strategy has increased the efficiency of our NBS programme by reducing FP and false negative results, second sample requests, and the time required for diagnosis. [ABSTRACT FROM AUTHOR]

Background: The causes of vitamin B12 (B12) deficiency are varied and mainly related to gastric disorders. Glossitis is a common oral manifestation of B12 deficiency and is often first seen by dentists. This study aimed to investigate the correlation between B12 deficiency‐related glossitis (B12‐def glossitis) and gastric serum biomarkers [gastrin‐17(G17), pepsinogen I (PGI), pepsinogen II (PGII), and anti‐Helicobacter pylori (H. pylori) antibodies], and preliminarily discuss the etiology of B12‐def glossitis. Methods: A cross‐sectional study was conducted in patients complaining of glossodynia, burning sensation, or severe recurrent oral ulcers, but patients with a history of gastrectomy were excluded. All subjects underwent a uniform oral examination and hematological tests. Results: Of 243 patients, 133 with B12‐def glossitis were in the case group, and 110 with other oral mucosal diseases (non‐glossitis) and normal B12 levels were in the control group. In the case group, 84.2% (112/133) showed high G17 and low PGI levels (G17hi PGIlow). Univariate logistic regression showed that G17hi PGIlow was a high‐risk factor for B12‐def glossitis (OR: 92.44; 95% CI: 35.91, 238.02). Subgroup analyses in the case group showed that the G17hi PGIlow group presented with lower B12 levels and a lower positive rate of anti‐H. pylori antibodies compared to the non‐G17hi PGIlow group. Conclusion: Gastric serum biomarkers in patients with B12‐def glossitis generally showed G17hi PGIlow, suggesting possible atrophy of gastric corpus and fundus mucosa. The G17hi PGIlow and non‐G17hi PGIlow groups may represent different etiologies of B12 deficiency. [ABSTRACT FROM AUTHOR]

Since the beginning of the 21st century, interest in vegan diets has been rapidly increasing in most countries. Misconceptions about vegan diets are widespread among the general population and health professionals. Vegan diets can be health-promoting and may offer certain important advantages compared to typical Western (and other mainstream) eating patterns. However, adequate dietary sources/supplements of nutrients of focus specific to vegan diets should be identified and communicated. Without supplements/fortified foods, severe vitamin B12 deficiency may occur. Other potential nutrients of focus are calcium, vitamin D, iodine, omega-3 fatty acids, iron, zinc, selenium, vitamin A, and protein. Ensuring adequate nutrient status is particularly important during pregnancy, lactation, infancy, and childhood. Health professionals are often expected to be able to provide advice on the topic of vegan nutrition, but a precise and practical vegan nutrition guide for health professionals is lacking. Consequently, it is important and urgent to provide such a set of dietary recommendations. It is the aim of this article to provide vegan nutrition guidelines, based on current evidence, which can easily be communicated to vegan patients/clients, with the goal of ensuring adequate nutrient status in vegans. [ABSTRACT FROM AUTHOR]

Chronic inflammatory enteropathy (CIE) in dogs, a spontaneous model of human inflammatory bowel disease (IBD), is associated with a high rate of cobalamin deficiency. The etiology of hypocobalaminemia in human IBD and canine CIE remains unknown, and compromised intestinal uptake of cobalamin resulting from ileal cobalamin receptor deficiency has been proposed as a possible cause. Here, we evaluated the intestinal expression of the cobalamin receptor subunits, amnionless (AMN) and cubilin (CUBN), and the basolateral efflux transporter multi-drug resistance protein 1 (MRP1) in 22 dogs with CIE in comparison to healthy dogs. Epithelial CUBN and AMN levels were quantified by confocal laser scanning microscopy using immunohistochemistry in endoscopic ileal biopsies from dogs with (i) CIE and normocobalaminemia, (ii) CIE and suboptimal serum cobalamin status, (iii) CIE and severe hypocobalaminemia, and (iv) healthy controls. CUBN and MRP1 expression was quantified by RT-qPCR. Receptor expression was evaluated for correlation with clinical patient data. Ileal mucosal protein levels of AMN and CUBN as well as mRNA levels of CUBN and MRP1 were significantly increased in dogs with CIE compared to healthy controls. Ileal cobalamin receptor expression was positively correlated with age, clinical disease activity index (CCECAI) score, and lacteal dilation in the ileum, inversely correlated with serum folate concentrations, but was not associated with serum cobalamin concentrations. Cobalamin receptor downregulation does not appear to be the primary cause of hypocobalaminemia in canine CIE. In dogs of older age with severe clinical signs and/or microscopic intestinal lesions, intestinal cobalamin receptor upregulation is proposed as a mechanism to compensate for CIE-associated hypocobalaminemia. These results support oral supplementation strategies in hypocobalaminemic CIE patients. [ABSTRACT FROM AUTHOR]

This document provides summaries of various medical research studies related to developmental medicine and child neurology. The studies cover a range of topics, including rare movement disorders, memory impairments in children with neonatal hypoxic-ischaemic encephalopathy, corpus callosum anomalies, pediatric functional neurological disorder, MOGAD, pediatric multiple sclerosis, DHDDS/NUS1-related neurodevelopmental disorders, Moebius syndrome, vitamin B12 deficiency, Miller-Fisher syndrome, and rapid trio genome sequencing in infants with epilepsy. The studies offer valuable insights into these conditions and highlight the need for specialized services and support for affected children. Additionally, the document discusses studies on genetic disorders and epilepsy, including rapid genetic sequencing, causal genetic networks, investigational treatments for Dravet syndrome, CASK-related disorders, and the benefits and potential harms of rapid whole genome sequencing. These studies provide valuable information on the diagnosis and treatment of these conditions. Furthermore, the document covers studies on the treatment of Type 1 spinal muscular atrophy with risdiplam, the transition of children with chronic health conditions into adult health services, the natural history of ataxia-telangiectasia, the effects of intra-erythrocyte dexamethasone phosphate in patients with ataxia-telangiectasia, and precision gene therapy for aromatic L-amino acid decarboxylase deficiency. These studies offer important findings on the safety and efficacy of treatments and the challenges in transitioning care for children with [Extracted from the article]

Optic neuritis is a rare presentation of vitamin B12 deficiency. We describe a 33-year-old female patient living with HIV presenting with progressive loss of vision for 1 week. She had a history of severe peripheral neuropathy that was managed with vitamin B12-containing tablets approximately three years before presenting with progressive loss of vision. On examination, she had no perception of light in the left eye and no perception of hand motion in the right eye. The fundus in her left eye had mild blurring of disc margins. Results from tests done showed a haemoglobin of 12.9g/dl, MCV 101fl, a serum vitamin B12 of 78pmol/l, and cytomegalovirus (CMV) test showed no active disease. She was diagnosed with optic neuritis and started on 30 mg tablets of prednisolone for 1 week with slight improvement. She was then started on vitamin B12 injections 1 mg daily for 10 days and thereafter, monthly for 6 months. She reported gradual improvement and regained her sight after 5 months treatment of with Vitamin B12 injections. Ophthalmic manifestations of vitamin B12 deficiency are not common and may present without haematological signs therefore, a high index of suspicion is required for early diagnosis and management of vitamin B12 deficiency. [ABSTRACT FROM AUTHOR]

Background: Macrocytosis, characterized by abnormally large red blood cells (RBCs), often indicated by elevated Mean Corpuscular Volume (MCV) in complete blood count (CBC), is a significant hematological finding. Diverse underlying pathologies, including megaloblastic and non-megaloblastic etiologies, contribute to macrocytosis. Understanding these causes is crucial for tailored management strategies. Aim: This study aimed to delineate macrocytic anemia into megaloblastic and non-megaloblastic subtypes through comprehensive hematological and biochemical analyses. Additionally, it sought to evaluate distinctive hematological features among different etiologies in macrocytic patients. Methods: A prospective observational study was conducted from January 2021 to November 2021 at MKCG Medical College and Hospital, Odisha, India. 350 adult patients with MCV = 100 fl were enrolled, and comprehensive hematological and biochemical analyses were performed. Patients were categorized into megaloblastic and non-megaloblastic groups based on identified etiological factors. Results: Of the enrolled patients, 162 (46.29%) were diagnosed with megaloblastic anemia, while 188 (53.71%) presented with non-megaloblastic macrocytosis. Significant differences were observed in various hematological and biochemical parameters between the two groups. Excessive alcohol intake was the most prevalent etiology among non-megaloblastic macrocytosis cases. Discussion: The study highlights the importance of evaluating macrocytosis, even in the absence of anemia, emphasizing thorough assessment for accurate diagnosis. Megaloblastic anemia was primarily associated with deficiencies in vitamin B12 and folate, while non-megaloblastic macrocytosis had diverse underlying pathologies, including liver diseases and alcohol consumption. Conclusion: Comprehensive evaluation of macrocytosis is essential for accurate diagnosis and management. Further research is warranted to optimize diagnostic strategies for this clinically significant condition. [ABSTRACT FROM AUTHOR]

Objective: There may be an association between hyperprolactinemia and autoimmune diseases, possibly because of the immunostimulatory effect of prolactin. The aim of this study was to investigate the prevalence of thyroid and non-thyroid autoimmune diseases, serum B-cell activating factor (BAFF), and proliferation-inducing ligand (APRIL) levels as indicators of increased autoimmunity, quality of life, depression, and anxiety in patients with prolactinoma. Methods: Fifty-six premenopausal women with prolactinoma and 50 healthy premenopausal women were included in the study. Autoimmune markers, including anti-nuclear antibody, rheumatoid factor immunoglobulin M (IgM) (RF-IgM), anti-double-stranded DNA (anti-dsDNA), anti-transglutaminase IgA (anti TG-IgA), and anti-Sjogren's syndrome A (anti-ssA), serum BAFF, APRIL and vitamin B12 levels, thyroid function tests, anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin and thyroid Doppler ultrasound, were evaluated. Short-form 36, Beck Depression Inventory, and Beck Anxiety Inventory tests were also used. Results: The prevalence of autoimmune thyroiditis (AIT) was 32.1% in the patient group, whereas the prevalence of newly diagnosed AIT was similar to controls (p>0.05). Vitamin B12 deficiency was higher in patients with prolactinoma than in controls (25.6% and 9.1%, p=0.016). Autoantibody positivity was found to be similar between the groups (35.7% and 28.1%, p=0.25). Serum BAFF and APRIL levels were not different in patients with prolactinoma than in controls (p>0.05). Quality of life, anxiety, and depression scores were not different between patients with or without AIT and those with or without positivity for any autoantibody (p>0.05). Conclusion: One-third of the patients were diagnosed with AIT and onefourth of the patients had vitamin B12 deficiency in our study. However, non-thyroid autoimmune diseases did not increase and no alterations were detected in serum BAFF/APRIL levels in patients with prolactinoma. [ABSTRACT FROM AUTHOR]

Introduction: The prevalence of vitamin B12 deficiency is high in at-risk populations with sometimes irreversible consequences. Beside total B12 (TVB12), active B12 (AVB12) is a promising first-line marker. Only Abbott AVB12 assays were largely evaluated and generally demonstrated benefit in clinical practice. More recently developed Roche AVB12 still requires some investigations. Objectives: Our study aimed to evaluate the Roche Elecsys® AVB12 immunoassay performance versus Roche Elecsys® TVB12 competition assay. Design: and Methods: We included 175 patients at Rouen University Hospital who had a TVB12 value <300 pmol/L. We evaluated performance of AVB12 by comparing the results with TVB12 and MMA values in case of disagreement. Results: Positive correlation was found between the AVB12 and TVB12. We found a disagreement between TVB12 and AVB12 in 18.8% of cases. Among 33 cases of disagreement, 76% had normal AVB12 but low TVB12, whereas 24% had low AVB12 and normal TVB12. Thirty-one MMA determinations were performed: 71% showed agreement between MMA and AVB12, versus 29% between MMA and TVB12. TVB12 reported a sensitivity (Se) at 66.7%, specificity (Sp) at 20%, positive predictive value (PPV) at 16.7% and negative predictive value (NPV) at 71.4% for the prediction of MMA elevation. We determined an optimized cut-off value of 45.5 pmol/L for AVB12, which reported a Se 66.7%, Sp 60%, PPV 30.7%, and NPV 88.9%. Conclusions: Our results provide preliminary evidence that Roche AVB12 may offer better discrimination than Roche TVB12 in the diagnosis of vitamin B12 deficiency. Further more detailed evaluation is warranted. [ABSTRACT FROM AUTHOR]

Maternal vitamin B12 deficiency has been associated with disturbed cognitive functioning in offspring at different ages during childhood. However, this association has not been explored in pre‐school‐age children. The objective of this study was to examine the association between maternal vitamin B12 levels at the beginning and end of pregnancy and cognitive functioning in their children at 4 years of age. This longitudinal prospective study included a subsample of pregnant women and their children aged 4 years (n = 249) who participated in the ECLIPSES Study conducted in the province of Tarragona, Spain, from 2013 to 2017. Maternal vitamin B12 concentrations were determined in the first and third trimesters, and sociodemographic, nutritional and psychological data were collected. The children's cognitive functioning was assessed using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI‐IV) and subtests of the Neuropsychological Assessment of Development (NEPSY‐II). The multivariable models showed a significant relationship between vitamin B12 and the working memory index in the first trimester of the pregnancy but not in the third trimester. Children of mothers in the second vitamin B12 level tertile (314–413 pg/mL) (β = 6.468, 95% confidence interval [CI]: = 2.054, 10.882, p = 0.004) and third vitamin B12 level tertile (≥414 pg/mL) (β = 4.703, 95% CI: = 0.292, 9.114, p = 0.037) scored higher in the working memory index of the WPPSI‐IV than the children of mothers with vitamin B12 levels in the first tertile (<314 pg/mL). Maintaining an adequate level of maternal vitamin B12 during early pregnancy contributes to improved performance in childhood working memory at 4 years of age. Key messages: Previous research suggests that maternal vitamin B12 deficiency may negatively affect the neurodevelopment of children at different ages.This study analyzes the effect of maternal serum vitamin B12 levels at the beginning and end of pregnancy on cognitive functioning in children at 4 years of age.In a population with good socioeconomic conditions and adequate nutritional status, maintaining an adequate level of maternal vitamin B12 during early pregnancy can improve the working memory of their children when they reach 4 years old.These findings emphasize the importance of screening for maternal vitamin B12 levels during this critical period of foetal programming to optimize cognitive functioning in offspring. However, further comprehensive and well‐designed long‐term studies are essential to validate and strengthen our results. [ABSTRACT FROM AUTHOR]

Background: Transcobalamin II (TCN2) defect is a rare metabolic disorder associated with a range of neurological manifestations, including mild developmental delay, severe intellectual disability, ataxia, and, in some cases, seizures. Cobalamin, an essential nutrient, plays a crucial role in central nervous system myelination. Clinical Presentation: We present a family with an index patient who exhibited progressive neurodevelopmental regression starting at 9 months of age, accompanied by myoclonic seizures, ataxia, and tremor. No significant hematological abnormalities were observed. Exome sequencing analysis identified a novel homozygous mutation, c.3G>A – P(Met1I), affecting the acceptor site of intron 4 of the TCN2 gene (chromosome 22: 31003321, NM_000355.4), leading to likely pathogenic variant potentially affecting translation. Following treatment with hydroxocobalamin, the patient demonstrated partial clinical improvement. He has a sibling with overt hematological abnormalities and subtle neurological abnormalities who is homozygous to the same mutation. Both parents are heterozygous for the same mutation. Conclusions: In infants presenting with unexplained non‐specific neurological symptoms, irrespective of classical signs of vitamin B12 deficiency, evaluation for TCN2 defect should be considered. Early diagnosis and appropriate management can lead to favorable outcomes. [ABSTRACT FROM AUTHOR]

The recreational use of nitrous oxide as laughing gas becomes a real public health issue among adolescents and young adults. Chronic use is deleterious and can lead to severe neurological disorders. Nitrous oxide inactivates vitamin B12, and the functional defect of vitamin B12 plays a major role in the pathogenesis of nitrous oxide-related neurological disorders. Here we report the case of a 22-year-old woman who came to the hospital after an unexplained loss of consciousness. She exhibited typical features of vitamin B12 or folate deficiency such as macrocytic anemia and hypersegmented neutrophils. However, serum concentrations of folate and vitamin B12 were normal. In contrast, circulating concentrations of total homocysteine and methylmalonic acid were significantly increased. These results clearly indicated a defect in vitamin B12 functions. The reason for this defect was clarified when she revealed that she had been consuming nitrous oxide recreationally for over a year. The present case points out the challenges in diagnosing vitamin B12 deficiency in the context of nitrous oxide abuse due to normal concentrations of total serum vitamin B12 in a significant proportion of cases. The medical community should be aware of how difficult it can be to interpret B12 status in this specific population. [ABSTRACT FROM AUTHOR]

Vitamin B12 (VitB12) is a micronutrient and acts as a cofactor for fundamental biochemical reactions: the synthesis of succinyl-CoA from methylmalonyl-CoA and biotin, and the synthesis of methionine from folic acid and homocysteine. VitB12 deficiency can determine a wide range of diseases, including nervous system impairments. Although clinical evidence shows a direct role of VitB12 in neuronal homeostasis, the molecular mechanisms are yet to be characterized in depth. Earlier investigations focused on exploring the biochemical shifts resulting from a deficiency in the function of VitB12 as a coenzyme, while more recent studies propose a broader mechanism, encompassing changes at the molecular/cellular levels. Here, we explore existing study models employed to investigate the role of VitB12 in the nervous system, including the challenges inherent in replicating deficiency/supplementation in experimental settings. Moreover, we discuss the potential biochemical alterations and ensuing mechanisms that might be modified at the molecular/cellular level (such as epigenetic modifications or changes in lysosomal activity). We also address the role of VitB12 deficiency in initiating processes that contribute to nervous system deterioration, including ROS accumulation, inflammation, and demyelination. Consequently, a complex biological landscape emerges, requiring further investigative efforts to grasp the intricacies involved and identify potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: Vitamins are involved in neurogenesis, a defense mechanism working in neurons, metabolic reactions, neuronal survival, and neuronal transmission. Previous studies have implicated role of Vitamin B12 and Vitamin D deficiency in formation of amyloid beta plaques and accumulation of synuclein in patients of Alzheimer's disease and Parkinson's disease. Aims: We conducted this study to estimate the deficiency of vitamin D and vitamin B12 in patients of Alzheimer's disease and Parkinson's disease and assess their clinical correlation. Methods: 83 patients of Parkinson's disease and Alzheimer's disease were recruited in the study as per a predefined inclusion criteria. Vitamin B12 and Vitamin D levels were tested in all patients included in the study. Results: 70 % patients of Alzheimer's disease and 75% patients of Parkinson's disease were found to have low levels of vitamin D; with significant correlation with the severity of dementia. Vitamin B12 deficiency was seen in 23.5% patients of Alzheimer's disease and 20.4% patients with Parkinson's disease. The severity of Vitamin B12 deficiency correlated significantly with severity of dementia in Parkinson's disease. Conclusion: Vitamin B12 and Vitamin D deficiency exists in patients with Alzheimer's disease and Parkinson's disease with linear correlation with the severity of dementia in these patients. [ABSTRACT FROM AUTHOR]

Objective: To study etiology and clinical profile of pancytopenia patients Design: Crosscectional study Setting: A large, academic, tertiary medical center Methodology: Clinicohematological parameters including laboratory data of all patients with a primary diagnosis of pancytopenia was taken. The various etiological factors, clinical presentations and lab investigations were taken into account and compared and prognosis was assessed for each patient Results: A male preponderance was observed, and the majority of patients were aged above 60 years. The most common clinical features were pallor and splenomegaly. Common PS finding was NCNC anaemia.67 percent of patients had hemoglobin less than 7 g%; whereas around 50% of the sample had WBC < 2000 and platelets less than 50000, 52 % had vitamin B12 deficiency, 32% had folic acid deficiency and 19% had a deficiency of both. The most common cause of pancytopenia was Vitamin B12 deficiency. Most common malignancy associated with pancytopenia was AML. Interpretation and conclusion: Several easily recognisable and treatable conditions can manifest as pancytopenia. Prompt management of such conditions, notably sepsis and megaloblastic anaemia, can result in the resolution of the cytopenias and negate the need for a BME. Pancytopenia investigations, when guided by appropriate cliniclaboratory findings, can promptly identify the underlying aetiology, while also identifying cases where an expedited BME is required. [ABSTRACT FROM AUTHOR]

Iron deficiency anemia is considered the leading cause of anemia during pregnancy; however, there is a lack of comprehensive studies on the etiological factors of anemia in pregnant women. The objective of this study was to systematically investigate the causes of anemia in pregnancy. Five hundred women with hemoglobin levels < 11 g/dl between 6 and 40 weeks of pregnancy underwent a complete hemogram, iron studies, serum folate, serum B12, serum copper, and serum zinc level assessments using standard methods. The median age of the patients was 26 years (range 24–29 years). The majority of patients were in the third trimester (449/500, 89.8%). Among the patients, 325 (65%) had vitamin B12 deficiency, with 159 (31.8%) having isolated B12 deficiency and 142 (28.4%) having combined B12 and iron deficiency. Isolated iron deficiency anemia was present in 74 patients (14.8%). Additionally, 28 patients (5.6%) had beta-thalassemia minor, and anemia of chronic disease was found in 17.2% (86) of the patients. Vitamin B12 deficiency was the most common cause of anemia, followed by combined B12 and iron deficiency. Further studies in diverse populations are warranted as they have broader implications for nutrient supplementation during pregnancy. [ABSTRACT FROM AUTHOR]

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Background: Diabetic people on metformin are more likely to develop vitamin B12 deficiency. There has been little research into the duration of therapy and dose of metformin that causes B12 deficiency and peripheral neuropathy. This study is being done to determine the same. Objective: To determine the association between vitamin B12 deficiency and its neuropathy to long-term metformin therapy in diabetic patients. Study design: This observational cross-sectional study was conducted at SRIHER Chennai. Patients on long-term metformin were taken and separated into two groups: B12 Vitamin deficiency and normal Vitamin B12 levels. Results: B12 Vitamin deficiency was found in 15.72% of 159 patients on metformin. Only 2 of the 59 people on vitamin supplements in our study showed Vitamin B-12 deficiency, whereas 23 out of 100 people in the non-supplemented group had Vitamin B-12 deficiency. The difference (OR - 0.11; P 0.005) was statistically important. There was a statistically important difference observed between the prevalence of deficiency of vitamin B-12, Duration (>5 years), and dosage (>1 g/day) of Metformin use (p-value - 5 years) and dose > 1g/day are linked to B12 Vitamin deficiency and neuropathy in diabetic patients.

Cobalamin C disease is the most common complementation class of cobalamin disorders. Here, we present a case of a 14-yr-old male with early-onset cblC disease and autism spectrum disorder (ASD) admitted to our inpatient medical service for behavioral decompensation. We use this case to highlight key aspects of the neurodevelopmental and neuropsychiatric disorders associated with cblC disease. By incorporating a comprehensive review of existing literature, we highlight salient domains of psychological impairment in cblC disease, discuss the full range of neuropsychiatric presentations, and review clinical management implications unique to cblC disease.

A case report published in the journal Bipolar Disorders describes a 48-year-old female patient who developed symptoms of mixed-state bipolar disorder after overdosing on vitamin B12. The patient experienced disorganized behavior, psychomotor agitation, sleep disturbances, depressed mood, and physical tics. She had no prior history of mood fluctuations or psychiatric treatment. The symptoms began after self-administering high doses of vitamin B12, which was recommended by a nurse and prescribed by a general practitioner. The patient underwent various treatments, including electroconvulsive therapy and medication, which provided temporary relief. The case suggests that vitamin B12 overdose may act as an environmental trigger for bipolar disorder in individuals with genetic susceptibility. However, further research is needed to understand the underlying mechanisms. [Extracted from the article]

Vitamin B12 deficiency-associated symptoms include fatigue, neurological symptoms such as tingling sensations, memory difficulties, and anemia. Certain populations face an elevated risk of vitamin B12 deficiency. For instance, vegetarians are susceptible to vitamin B12 deficiency due to the absence of animal-derived foods in their diet. Similarly, older adults and individuals with gastrointestinal disorders like Crohn's disease or celiac disease are more likely to experience malabsorption issues, predisposing them to an increased risk of vitamin B12 deficiency. Furthermore, individuals with a history of total gastrectomy are exceptionally predisposed to developing vitamin B12 deficiency. This case report presents the case of an 80-year-oldwoman who underwent total gastrectomy and esophagectomy with ileum-right colon reconstruction and severe vitamin B12 deficiency. She exhibited general weakness and rapidly progressing cognitive impairment. We also reviewed the literature to provide current insights into the symptoms, risk factors, and treatments. [ABSTRACT FROM AUTHOR]

Abstract Imerslund-Gräsbeck syndrome (IGS) is a rare autosomal recessive disorder characterized by vitamin B12 malabsorption. Most patients present with non-specific symptoms attributed to vitamin B12 deficiency, and proteinuria. Patients may if untreated, develop severe neurocognitive manifestations. If recognized and treated with sufficient doses of vitamin B12, patients recover completely. We provide, for the first time, an overview of all previously reported cases of IGS. In addition, we provide a complete review of IGS and describe two new patients.

Anemia and iron deficiency (ID) are common complications in patients with pancreatic ductal adenocarcinoma (PDAC), but their underlying causes remain unclear. This study investigated the incidence and characteristics of anemia and micronutrient deficiencies in PDAC patients before initiating chemotherapy. A total of 103 PDAC patients were included, comprising 67 in the palliative and 36 in the adjuvant groups. The overall incidence of anemia was 42.7% (n = 44), with comparable rates in both groups. Normocytic and normochromic anemia were predominant, with mild and moderate cases observed in 32% and 10.7% of the cohort, respectively. ID was evident in 51.4% of patients, with absolute ID more frequent in the adjuvant than in the palliative group (19.4% vs. 13.4%). Functional ID occurred more often in the palliative than in the adjuvant group (41.8% vs. 25%). Vitamin B12 and folate deficiency occurred in n = 5) of patients. Furthermore, 8.7% (n = 9) of patients had chronic kidney disease and anemia. To elucidate mechanisms of iron deficiency, the study explored the expression of iron regulators (hepcidin (HEP), ferroportin (FPN), and ZIP14 protein) and mitochondrial mass in PDAC tissue with immunohistochemical (IHC) staining and Perl’s Prussian blue to detect iron deposits on available tumor samples (n = 56). ZIP14 expression was significantly higher in less advanced tumors (p = 0.01) and correlated with mitochondrial mass (p < 0.001), potentially indicating its role in local iron homeostasis. However, no significant impact of tissue iron regulators on patient survival was observed. Perl’s Prussian blue staining revealed iron deposits within macrophages, but not in pancreatic duct cells. Furthermore, the GEPIA database was used to compare mRNA expression of iron regulators (HEP, FPN, and ZIP14) and other genes encoding iron transport and storage, including Transferrin Receptor Protein 1 (TfR1) and both ferritin chain subunits (FTH and FTL), in PDAC and normal pancreatic samples. FPN, TfR1, FTH, and FTL showed higher expression in tumor tissues, indicating increased iron usage by cancer. ZIP14 expression was higher in the pancreas than in PDAC and was correlated with FPN expression. The study highlights the importance of baseline iron status assessment in managing PDAC patients due to the high incidence of anemia and iron deficiency. Furthermore, ZIP14, in addition to HEP and FPN, may play a crucial role in local iron homeostasis in PDAC patients, providing valuable insights into the underlying mechanisms of iron dysregulation.

Parkinson’s disease (PD) is a progressive neurodegenerative disease with various clinical manifestations, its origin not always can be explained only by dopamine deficiency. Long-term treatment with levodopa (especially its intraduodenal administration), as well as clinical manifestations of polyneuropathy, cognitive deficits, postural disorders with freezing of gate, REM sleep behavioral disorders, are more often associated with vitamin B12 deficiency. Several reasons for this association and mechanisms of their development are discussed. Early detection of cobalamin deficiency in PD, especially in patients from high-risk groups, makes it possible to stop this pathological condition timely and prevent irreversible changes. Modern data on the use of high-dose (1000 μ g) oral vitamin B12 are presented, it has comparable clinical efficacy and significant advantages, compared with the parenteral form, in terms of the ease of use and the ability to avoid undesirable postinjection reactions.

Abstract Background Type 1 diabetes mellitus (T1DM) is a lifelong diagnosis that involves immune-mediated damage of pancreatic beta cells and subsequent hyperglycemia, manifesting as: polyuria, polydipsia, polyphagia, and weight loss. Treatment of type 1 diabetes centers on insulin administration to replace or supplement the body's own insulin with the goal of achieving euglycemia and preventing or minimizing complications. Patients with T1DM are at risk for developing other autoimmune conditions, most commonly thyroid or celiac disease. Case presentation A 20-year-old African American female with T1DM was referred by her endocrinologist to pediatric gastroenterology for 2 months of nocturnal, non-bloody diarrhea, left lower quadrant pain, and nausea; she was also being followed by neurology for complaints of lower extremity paresthesias and pain. The patient’s initial lab-workup was remarkable for a low total Immunoglobulin A (IgA) level of

Anemia, a common symptom in pregnancy, can lead to life-threatening cardiomyopathy. A 30-years old gravida 2 para 1 woman was admitted at 34 weeks of gestational age with asymptomatic pancytopenia and vitamin B12 deficiency in the laboratory tests. She also had a diet-controlled gestational diabetes, megaloblastic changes in Bone marrow aspiration and cardiomyopathy shown by echocardiography. The patient recovered from pancytopenia and cardiomyopathy after one week treatment with vitamin B12 and folate. In this case, cardiomyopathy worsened with anemia. By treating vitamin B12 deficiency, cardiomyopathy can be prevented or controlled during pregnancy. Careful consideration is needed when assessing anemia in pregnant women on vegetarian diet and at higher risk.

Although nitrous oxide (N2O) has long been used as an anesthetic, it’s use as a recreational drug has recently increased. As N2O abuse is associated with a number of adverse health effects, it has become a significant public health issue. Chronic abuse can lead to a number of neurological complications, most commonly related to functional vitamin B12 deficiency. One of the most encountered forms of N2O neurotoxicity is a subacute combined degeneration, which can cause permanent neurological damage. The medical community should therefore be aware of the increasing scale of recreational N2O exposure and the possible complications of this drug abuse. Early recognition and treatment of N2O toxicity are crucial. We present the case of an 18-year-old male who was diagnosed with subacute combined spinal cord degeneration related to N2O abuse.

Summary: Background: The high variability in clinical and metabolic presentations of inborn errors of cobalamin (cbl) metabolism (IECM), such as the cblC/epicblC types with combined deficits in methylmalonyl-coA mutase (MUT) and methionine synthase (MS), are not well understood. They could be explained by the impaired expression/activity of enzymes from other metabolic pathways. Methods: We performed metabolomic, genomic, proteomic, and post-translational modification (PTM) analyses in fibroblasts from three cblC cases and one epi-cblC case compared with three cblG cases with specific MS deficits and control fibroblasts. Findings: CblC patients had metabolic profilings consistent with altered urea cycle, glycine, and energy mitochondrial metabolism. Metabolomic analysis showed partial disruption and increased glutamate/ketoglutarate anaplerotic pathway of the tricarboxylic acid cycle (TCA), in patient fibroblasts. RNA-seq analysis showed decreased expression of MT-TT (mitochondrial tRNA threonine), MT-TP (mitochondrial tRNA proline), OXCT1 (succinyl CoA:3-oxoacid CoA transferase deficiency), and MT-CO1 (cytochrome C oxidase subunit 1). Proteomic changes were observed for key mitochondrial enzymes, including NADH:ubiquinone oxidoreductase subunit A8 (NDUFA8), carnitine palmitoyltransferase 2 (CPT2), and ubiquinol-cytochrome C reductase, complex III subunit X (UQCR10). Propionaldehyde addition in ornithine aminotransferase was the predominant PTM in cblC cells and could be related with the dramatic cellular increase in propionate and methylglyoxalate. It is consistent with the decreased concentration of ornithine reported in 3 cblC cases. Whether the changes detected after multi-omic analyses underlies clinical features in cblC and cblG types of IECM, such as peripheral and central neuropathy, cardiomyopathy, pulmonary hypertension, development delay, remains to be investigated. Interpretation: The omics-related effects of IECM on other enzymes and metabolic pathways are consistent with the diversity and variability of their age-related metabolic and clinical manifestations. PTMs are expected to produce cumulative effects, which could explain the influence of age on neurological manifestations. Funding: French Agence Nationale de la Recherche (Projects PREDICTS and EpiGONE) and Inserm.

Background: Late-onset cobalamin C (cblC) deficiency is associated with a wide range of neurological and psychiatric symptoms, hematological manifestations, anorexia, renal failure, ocular abnormalities, dermatitis, and pancreatitis. However, the neuroimaging characteristics of late-onset cblC deficiency remain insufficiently documented. Common findings include diffuse white matter swelling, varying degrees of severe leukoaraiosis, hydrocephalus, corpus callosum atrophy, and symmetric bilateral basal ganglia lesions. In this report, we present a case of late-onset cblC deficiency in adults presenting with cerebellar ataxia as the primary symptom. The MRI findings revealed bilateral lateral cerebellar hemispheres exhibiting symmetric hyperintensity, primarily observed in diffusionweighted imaging (DWI), which is a rarely reported imaging change in this context. Case presentation: Our patient was a male who experienced symptoms starting at the age of 30 years, including unsteady walking, apparent cerebellar ataxia, and cognitive impairment upon nervous system examination. Brain magnetic resonance imaging (MRI) exhibited symmetric hyperintensity in the bilateral lateral cerebellar hemispheres, predominantly manifested in DWI, without any enhancement. Subsequently, significantly elevated blood total homocysteine and urinary methylmalonic acid levels were observed. Genetic analysis confirmed the presence of MMACHC compound heterozygous mutants c.482G > A and c.609G > A, thus confirming the diagnosis of cblC deficiency. These variants were classified as likely pathogenic following the guidelines of the American College of Medical Genetics and Genomics (ACMG) and were verified using Sanger sequencing. Following treatment, the patient experienced improvements in walking ability and cognition, a significant decrease in blood total homocysteine levels, and reversal of the imaging lesions. In conclusion: Late-onset cblC deficiency presents with diverse clinical and imaging manifestations. Early diagnosis and treatment are crucial in achieving a favorable prognosis. This case serves as a reminder to clinicians not to overlook genetic metabolic disorders, particularly those causing multisite damage, in adult patients with undiagnosed neurological disorders, especially those affecting the cerebellum. Notably, methylmalonic acidemia should be considered within the spectrum of bilateral cerebellar lesions. [ABSTRACT FROM AUTHOR]

Background: As we are aware that chronic liver disease frequently associated with haematological abnormalities which presents Anaemia of diverse etiology occurs in about 75% of patients and also this condition may be exacerbated by deficiency of folic acid and/or vitamin B12 that can occur secondary to inadequate dietary intake or malabsorption. So In this study we want to evaluate chronic liver disease patients having anaemia without overt bleeding in the past 3 months to know the severity and type of anaemia in these patients so as to enable us better management and decrease associated morbidity and mortality. Research Question: What is the scenario of anaemia in the spectrum of chronic liver disease in our setup? The setting of the study was at department of Gastroenterology, Government General Hospital, Guntur Medical College, Guntur, Andhra Pradesh. A one year observational study was conducted during the period from April 2022 to May 2023 on about 100 chronic liver disease patients having anaemia whose Hb levels <10 g/dl without overt bleeding in the past 3 months admitted during the above period in the department of Gastroenterology by studying their socio-demographic profiles, type of chronic liver disease and anaemia with related laboratory investigations etc. Results: It was observed that in ALC the most common anaemia is folic acid deficiency (39.7%) followed by Iron deficiency (37.2%), in HBV most common anaemia was Iron deficiency (54.5%) followed by Folic acid deficiency (36.4%), in HCV both Iron and Folic acid deficiency were equally distributed (42.9%) and in NAFLD Iron and B12 deficiency were equally distributed (25%). Regarding severity, about 14% were severely anaemic flowed by 63% moderately anaemic and 23% were mild anaemic as noticed. In this study among the ALC cases maximum 35.9% were belong to the age group 41-50 years followed by 45.5% belong to 51-60 among HBV, 42.9% belong to 41-50 years among HCV and about 50% of cases belong to 41-50 years among NAFLD. Totally it was observed that the majority age group suffering from chronic liver disease was between 41 -60 years. Mean age of study subjects was 46.7 years. And the lowest mean values of serum iron (29.29 mcg/dl) and folic acid (4.59ng/ml) was observed among HCV cases and serum vit-B12 (221.3 pg/ml) seen in ALC cases in this study. [ABSTRACT FROM AUTHOR]

The immune system has a role in neuropathic pain which includes autoimmune mechanisms (e.g., autoantibodies). Clinical studies have identified a number of conditions where neuropathic pain is common and that are associated with autoantibodies targeting antigens within the nervous system. Interestingly sensory symptoms can be relieved with immunotherapies or plasma exchange, suggesting that pain in these patients is antibody-mediated. Recent preclinical studies have directly addressed this. For example, passive transfer of CASPR2 autoantibodies from patients cause increased pain sensitivity and enhanced sensory neuron excitability in mice confirming pathogenicity and demonstrating that patient autoantibodies are a mechanism to cause neuropathic pain. Small fiber neuropathy (SFN) exclusively affects small sensory fibers (typically nociceptors) and is characterized by severe neuropathic pain. Known causes include diabetes, B12 deficiency and rare variants in sodium channel genes, although around 50% of cases are idiopathic. SFN is associated with autoimmune conditions such as Sjorgen's syndrome, Sarcoidosis and Celiac disease and immunotherapy in the form of Intravenous immunoglobulin (IVIG) has proved an effective treatment. Autoantibodies have been identified and, in some cases, passive transfer of SFN patient IgG in mice can recapitulate neuropathic pain-like behavior. Here we will discuss clinical and preclinical data relating to the idea that pathogenic autoantibodies contribute to SNF. We discuss putative pathogenic antibodies, cellular targets and the molecular mechanisms by which they cause sensory neuron damage and the development of neuropathic pain. Finally, we will comment on future directions which may provide further insights into the mechanisms underlying SFN in patients. [ABSTRACT FROM AUTHOR]

Background: Coexisting pathologies is not a new phenomenon and can cause diagnostic difficulties when they overshadow one another. They may alter the cytomorphology of cells and the machine readings to an extent that the actual diagnosis is missed. One such scenario is created by coexisting megaloblastic anemia and beta-thalassemia trait where the RBC indices and the hemoglobin chromatogram findings conform to neither of the two. Case presentation: We present two cases of anemia presenting with normocytic normochromic indices, increased red cell distribution width (RDW), elevated HbA2 levels and moderately high HbF levels in both of them and an additional low HbA1c in case 2. Upon evaluation of peripheral smear and biochemical tests, a non-immune hemolytic component was also identified with deficient Vit B12 levels in case 1 and highly elevated levels post-supplementation in case 2. Conclusions: Taking together the peripheral smear, erythrogram, chromatogram and biochemical findings, it was deduced that the alterations were caused by coexisting beta-thalassemia trait and megaloblastic anemia. Vit B12 deficiency was the cause behind hemolysis owing to intramedullary destruction of abnormal precursors. Upon supplementation in case 2, the immediate reticulocyte response was the reason behind spuriously low HbA1c. [ABSTRACT FROM AUTHOR]

Methylation is a ubiquitous and permanent key biochemical process playing a major role in gametogenesis and embryogenesis in relation to epigenetics and imprinting. Methylation relies on a unique cofactor S-Adenosyl Methionine: SAM. Release of the methyl group onto target molecules is followed by liberation of S-Adenosyl Homocysteine (SAH), and then homocysteine (Hcy), both potent inhibitors of the methylation process. Defective recycling of homocysteine, leading to Hyperhomocysteinemia, is mainly due to reduced activity of MTHFR (Methylene TetraHydroFolate Reductase). However, we described here, in a woman attending an ART program, a rather rare syndrome: The Folate trap syndrome. Due to vitamin B12 deficiency (malabsorption), Hcy cannot be recycled to methionine by the methionine synthase. Transmethylation activity is weak and leads to Hhcy (Hyperhomocysteinhemia). Her Hhcy, over 16µM, was resistant to 5MTHF (5 Methyltetrahydrofolate) associated with a support of the one carbon cycle, a classical efficient treatment for elevated homocysteine. Treatment with Methylcobalamine (associated with adenosyl Cobalamine) allowed a Hcy drop down to 10 µM. Knowing the pleiotropic negative impact of Hcy on gametes, embryos and pregnancy in general, we strongly recommend a Hcy dosage in both members of couples seeking treatment for pregnancy. [ABSTRACT FROM AUTHOR]

Vitamin B12 deficiency is common in older people and is linked to anaemia, cognitive decline, and dementia. Clinical presentation is variable, ranging from no symptoms or subtle, non‐specific symptoms, through to serious, irreversible neurological symptoms if left untreated. Although common, it is often under‐recognised, with diagnosis usually occurring on incidental blood test screening. Older people are at increased risk of vitamin B12 deficiency due to insufficient dietary intake, malabsorption associated with aged‐related changes in gastrointestinal function, higher incidence of pernicious anaemia, and chronic use of interfering medications such as metformin and proton‐pump inhibitors. Early detection and treatment in symptomatic deficiency are crucial to prevent irreversible damage. Vitamin B12 intramuscular injection bypasses potential absorption issues and is traditionally the first‐line treatment in older people. However, emerging evidence suggests that high‐dose oral replacement may be as effective. Older people often require lifelong therapy due to the irreversible nature of the underlying cause of deficiency. This review provides an overview of vitamin B12 deficiency and its management in older people. [ABSTRACT FROM AUTHOR]

Vitamin B12 deficiency and insufficiency can lead to both hematological and neurological impairments. This review examines nondisease causes and risk factors associated with dietary availability, such as eating habits, food processing, cooking techniques, and bioavailability, as well as increased physiological needs and iatrogenic factors linked to medication use or surgical procedures. As a result of these nondisease influences, groups at higher risk include vegans, vegetarians, older adults, individuals with limited diets, breastfed and preterm infants, and those who primarily consume foods prepared or cooked in ways that reduce vitamin B12 content, as well as individuals on certain medications or who have undergone specific surgeries. Recognizing these diverse risk factors helps develop strategies for prevention and intervention to minimize the adverse health effects related to B12 deficiency and insufficiency. [ABSTRACT FROM AUTHOR]

Vitamin B12 is a micronutrient required for hematopoietic, neuro-cognitive and cardiovascular function. Biochemical and clinical vitamin B12 deficiency has been recognized in patients with type 2 diabetes mellitus. One of the adverse effects of long-term metformin use is vitamin B12 malabsorption. Aim of the study was to assess the state of vitamin B12 deficiency in people with type 2 diabetes and to ascertain the relationship between vitamin B12 status, metformin use and peripheral neuropathy. It is a retrospective study that was conducted on 8040 subjects included 2126 type 2 diabetic patients, and 5914 nondiabetic individuals. Personal information, medical history, including metformin and multivitamin therapy use as well as the existence of clinical peripheral neuropathy, were all included data. For the purpose of measuring the amount of vitamin B12, blood samples were taken. Serum B12 levels <200 pg/ml was defined as B12 deficiency. Vitamin B12 deficiency was detected in 12.9% of diabetic group and 19.9% of control group. The mean value of vitamin B12 level between diabetic (563 ± 470.6 pg/ml) and non-diabetic (429.7 ± 310.9 pg/ml) showed a high significant difference, p value <0.001. The vitamin B12 levels were higher in people with diabetes. Vitamin B12 deficiency was not associated with metformin intake or diabetic neuropathy. Vitamin B12 level was significantly higher in diabetic compared to nondiabetic individuals. Neither peripheral neuropathy, anemia nor metformin therapy was associated with vitamin B12 deficiency. Vitamin B12 supplementation is not recommended as a routine practice in people with diabetes. This is contrary to the common practice that is sometimes done. The cost of supplementation can be used to provide more beneficial services and drugs for these people. [ABSTRACT FROM AUTHOR]