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Chronic inflammatory demyelinating polyneuropathy (CIDP) during pregnancy presents diagnostic and management challenges. We report a case of a primigravida in her 30s, exhibiting progressive quadriparesis starting in the second trimester. Initially, her symptoms of weakness, numbness and progressive quadriparesis were attributed to vitamin B12 deficiency, leading to the administration of intramuscular methylcobalamin injection. After referral to our tertiary care centre at 37 weeks of pregnancy and after further evaluation, neurological examination revealed findings characteristic of CIDP, which were confirmed by nerve conduction studies showing typical features of the condition. Treatment included intravenous methylprednisolone followed by intravenous immunoglobulin. An elective caesarean section was carried out because the patient was unable to effectively participate in labour due to her condition. The patient exhibited improved limb power postoperatively after immunoglobulin therapy. Challenges include delayed diagnosis, treatment initiation and management decisions. Multidisciplinary collaboration is crucial for optimal outcomes in CIDP during pregnancy., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Vitamin B12 deficiency is a recognised cause of neurological manifestations, including peripheral neuropathy, behavioural changes, and seizures. However, developmental and epileptic encephalopathy due to vitamin B12 deficiency is very rare. Here, we report an infant with vitamin B12-responsive developmental and epileptic encephalopathy due to a novel mutation in the fucosyltransferase 2 (FUT2) gene responsible for vitamin B12 absorption., Case Presentation: An 11-month-old girl of non-consanguineous parents presented with recurrent episodes of seizures since four months. Her seizures started as flexor epileptic spasms occurring in clusters resembling infantile epileptic spasms syndrome with hypsarrhythmia in the electroencephalogram. She was treated with multiple drugs, including high-dose prednisolone, vigabatrin, sodium valproate, levetiracetam and clobazam, without any response, and she continued to have seizures at 11 months. She had an early developmental delay with maximally achieving partial head control and responsive smile at four months. Her development regressed with the onset of seizure; at 11 months, her developmental age was below six weeks. On examination, she was pale and had generalised hypotonia with normal muscle power and reflexes. Her full blood count and blood picture revealed macrocytic anaemia with oval and round macrocytes. Bone marrow aspiration showed hypercellular marrow erythropoiesis with normoblastic and megaloblastic maturation. Due to the unusual association of refractory epilepsy and megaloblastic anaemia, a rare genetic disease of the vitamin B12 or folate pathways was suspected. The whole exome sequencing revealed a homozygous missense variant in exon 2 of the FUT2 gene associated with reduced vitamin B12 absorption and low plasma vitamin B12 levels, confirming the diagnosis of vitamin B12 deficiency related developmental and epileptic encephalopathy. She was started on intramuscular hydroxocobalamin, for which she showed a marked response with reduced seizure frequency., Conclusion: We report a novel variant in the FUT2 gene associated with vitamin B12-responsive developmental and epileptic encephalopathy and megaloblastic anaemia. This case report highlights the importance of timely genetic testing in children with refractory developmental and epileptic encephalopathy to identify treatable causes., (© 2024. The Author(s).)

Background: Imerslund-Gräsbeck syndrome (IGS) is an autosomal recessive disorder characterized by selective vitamin B12 malabsorption, resulting in vitamin B12 deficiency and impaired reabsorption of proximal tubular proteins.This case highlights a previously unidentified compound heterozygous variant in the Amnionless (AMN) gene that causes IGS syndrome and underscores the importance of long-term oral vitamin B12 replacement therapy in managing the condition., Case Presentation: In this retrospective analysis, we present the clinical data of a 3-year and 6-month-old female child diagnosed with IGS at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China, in November 2018. The child was admitted to the hospital due to a history of anemia persisting for over a month. There was no previous significant medical history. The admission examination revealed megaloblastic anemia with proteinuria. Serum vitamin B12 levels were decreased, while folic acid and renal function were normal. The patient was diagnosed with megaloblastic anemia and started long-term oral vitamin B12 replacement therapy. Throughout the follow-up period, blood tests consistently showed normal results, while proteinuria persisted. In November 2019, the child and her parents underwent whole exome sequencing analysis, which revealed a novel compound heterozygous variant in the AMN gene: c.162 + 1G > A and c.922 C > T (p.Q308X) in the child, c.162 + 1G > A in the father, and c.922 C > T (p.Q308X) in the mother. Therefore, this child was further diagnosed with IGS., Conclusions: In this case, whole exome sequencing proves to be highly practical in daily healthcare for diagnosing and refining rare or ultra-rare diseases with ambiguous phenotypes or genetic diversity. It is also valuable for prognostic evaluation and personalized management. Additionally, the oral vitamin B12 treatment demonstrated positive clinical effects for the child, offering a new option for patients unable to undergo intramuscular vitamin B12 replacement therapy., (© 2024. The Author(s).)

Background: No prospective study has evaluated the efficacy of oral supplementation with cobalamin in hypocobalaminemic cats., Objectives: To investigate the efficacy of oral or SC supplementation with cyanocobalamin in normalizing serum cobalamin and methylmalonic acid (MMA) concentrations in hypocobalaminemic cats with chronic gastrointestinal disease (CGID) or exocrine pancreatic insufficiency (EPI)., Animals: Forty-eight client-owned hypocobalaminemic (<290 ng/L) cats with normal or abnormally high serum MMA concentrations., Methods: This study was conducted based on the prospective randomized clinical trial method. Cats with CGID or EPI were randomly assigned to 2 groups that received either oral or SC supplementation with cobalamin (250 μg/cat) for 12 and 10 weeks, respectively, in addition to other medical and dietary interventions. Each cat was evaluated 3 times (baseline, 6-week postsupplementation, and 1-week postcompletion) by measuring serum cobalamin and MMA concentrations., Results: In cats with CGID or EPI, cobalamin concentrations were normalized in all cats that received either oral or SC supplementation (mean 100% [95% CI: 80.6%-100%] in both groups in cats with CGID and 100% [67.6%-100%] in both groups in cats with EPI). Among 37 cats with elevated MMA concentrations at baseline (21 cats with CGID and 16 cats with EPI), MMA concentrations were normalized in most cats with CGID (70% in oral and 82% in SC group) or EPI (88% in both groups)., Conclusions and Clinical Importance: In hypocobalaminemic cats with CGID or EPI, in conjunction with other medical and dietary interventions, both oral and SC supplementation are effective at normalizing serum cobalamin and MMA concentrations., (© 2024 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Healthy plant-based diets, such as the lacto-ovo-vegetarian and the vegan diet, offer numerous benefits to human health. Poorly designed plant-based diets, however, bear the risk for vitamin- and micronutrient deficiencies. Vitamin B12 (B12, cobalamin) is a nutrient of particular concern in both diets, and should be readily supplemented on a continuous basis to ensure adequate B12 levels and to prevent deficiencies., Case Report: This case reports describes the history of a healthy man in his mid-30s who adopted a vegan diet approximately 10 y ago. Well informed about the risks of vitamin B12 deficiency on a plant-based diet, he regularly supplemented methylcobalamin for years (single oral dose: 500 µg, 3-4 times a week) in order to maintain an adequate vitamin B12 status. In late 2023, however, he decided to cease B12 supplementation for undisclosed reasons. Subsequent to this decision, we closely monitored his B12 status and longitudinally measured serum B12, homocysteine, and holotranscobalamin (holo-TC). Total serum folate was also determined as it is a modifier of homocysteine concentration. A gradual decrease in holo-TC and vitamin B12 levels was observed after 4 weeks and supplements had to be re-introduced after 16 weeks. Homocysteine increased concomitantly up to 18.2 μmol/L after 20 weeks., Conclusions: While a short-term B12 supplement intake cessation might be well tolerated by vegans with an adequate B12 status, an interruption of more than 8 weeks could signify B12 loss approaching suboptimal status. This case report reiterates the need for continuous B12 supplementation in persons following an unfortified plant-based diet., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

This case report presents a male in his 30s with pernicious anaemia, initially diagnosed with autoimmune haemolytic anaemia and thrombocytopenia. Despite improvement with treatment, he developed bilateral leg weakness and numbness, ultimately diagnosed as peripheral neuropathy. Further investigations revealed a spectrum of haematological and neurological manifestations associated with B12 deficiency, challenging the typical illness script of pernicious anaemia. This report underscores the importance of recognising variations in clinical presentation and highlights the need for expanded illness scripts to guide accurate diagnosis and management., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: Vitamin B 12 deficiency is common in the elderly population. Standard treatment via intramuscular injections, however, has several disadvantages. Safer and more convenient dosage forms such as intranasal are therefore being explored. This study compares the effects of two intranasal vitamin B 12 dosage regimens in elderly vitamin B 12 -deficient patients., Methods: Sixty patients ≥65 years were randomly assigned to either a loading dose (daily administration for 14 days followed by weekly administration) or a no loading dose (administration every 3 days) regimen for 90 days. Each dose contained 1000 μg cobalamin. Total vitamin B 12 , holotranscoblamin (holoTC), methylmalonic acid (MMA) and total homocysteine (tHcy) levels in serum were measured on days 0, 7, 14, 30, 60 and 90., Results: Both dosage regimens resulted in a rapid increase of vitamin B 12 and holoTC concentrations and normalization of initial high, MMA and tHcy concentrations. The loading dose regimen resulted in the fastest and greatest increase to a median vitamin B 12 of 1090 pmol/L (reference 350-650 pmol/L) concentration after 14 days. Following weekly administration, B 12 rapidly decreased to a median concentration of 530 pmol/L after 90 days. The no loading dose regimen resulted in a steady increase to a median vitamin B 12 of 717 pmol/L after 90 days., Conclusions: Intranasal vitamin B 12 administration is an effective and suitable way to replenish and sustain vitamin B 12 levels in elderly patients., (© 2024 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: Vitamin B12 is primarily transported from plasma to cells by Transcobalamin. Deficiency of Transcobalamin is a rare autosomal recessive disorder that results in unavailability of cobalamin in cells and accumulation of homocysteine and methylmalonic acid., Case Report: We report a case of a 2-year-old male child with persistent pancytopenia, recurrent infections, and megaloblastic anemia. Next-generation sequencing identified a novel variant in exon 8 of TCN2 gene. Substantial improvement has been observed following administration of high doses of parenteral methylcobalamin., Conclusion: In patients with unresolved pancytopenia and megaloblastic anemia, Transcobalamin deficiency should be investigated and treated promptly to prevent any irreversible and harmful outcome., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Whether the long-term treatment of patients with proton pump inhibitors (PPIs) with different diseases [GERD, Zollinger-Ellison syndrome (ZES), etc.] can result in vitamin B 12 (VB 12 ) deficiency is controversial. In this study, in 175 patients undergoing long-term ZES treatment with anti-acid therapies, drug-induced control acid secretory rates were correlated with the presence/absence of VB 12 deficiency, determined by assessing serum VB 12 levels, measurements of VB 12 body stores (blood methylmalonic acid (MMA) and total homocysteine[tHYC]), and other features of ZES. After a mean of 10.2 yrs. of any acid treatment (5.6 yrs. with PPIs), 21% had VB 12 deficiency with significantly lower serum and body VB 12 levels ( p < 0.0001). The presence of VB 12 deficiency did not correlate with any feature of ZES but was associated with a 12-fold lower acid control rate, a 2-fold higher acid control pH (6.4 vs. 3.7), and acid control secretory rates below those required for the activation of pepsin (pH > 3.5). Over a 5-yr period, the patients with VB 12 deficiency had a higher rate of achlorhydria (73% vs. 24%) and a lower rate of normal acid secretion (0% vs. 49%). In conclusion, in ZES patients, chronic long-term PPI treatment results in marked acid hyposecretion, resulting in decreased serum VB 12 levels and decreased VB 12 -body stores, which can result in VB 12 deficiency.

Vitamin B12 and folate deficiency are reversible causes of megaloblastic anemia . Strict vegetarians are at risk of megaloblastic anemia due to low cobalamin in their diet . Knuckle hyperpigmentation in patients with megaloblastic anemia is due to excess melanin synthesis in skin. Here we present a case of a young vegetarian male with megaloblastic anemia with knuckle hyperpigmentation managed successfully with intravenous followed by oral vitamin b12 and folate supplementation., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The etiology of cerebral venous sinus thrombosis (CVST) is multifactorial. Although many acquired and genetic factors have been recognized as risk factors, hyperhomocysteinemia (hHcy) is independently associated with CVST. We describe three cases of CVST in this case series. All of them presented with headache. Two patients had papilledema and visual disturbances. On evaluation, there was CVST, and prothrombotic workup showed hHcy. In addition, two of them reported very low Vitamin B12 levels. All of them were treated with low-molecular-weight heparin followed by oral anticoagulation and Vitamin B6, B9, and B12 supplements. All of them responded to treatment, and follow-up imaging studies in two of them showed resolution of thrombosis. hHcy should be considered in the evaluation of CVST, especially in the setting of a pure vegetarian diet. Fortification of the diet with Vitamin B12 may be considered the majority of Indians consume predominantly vegetarian food., (Copyright © 2024 Copyright: © 2024 Annals of African Medicine.)

Background: The absorption of vitamin B12 is hindered in pernicious anemia (PA) owing to intrinsic factor deficiency. Traditionally, intramuscular vitamin B12 injections were the standard treatment, bypassing the impaired absorption. Although there is potential for oral vitamin B12 supplementation through passive enteral absorption, it is not commonly prescribed in PA owing to limited studies assessing its efficacy., Objectives: We aimed to assess the efficacy of oral vitamin B12 supplementation in PA., Methods: We enrolled participants diagnosed with incident vitamin B12 deficiency related to PA. The diagnosis of PA was based on the presence of classical immune gastritis and of anti-intrinsic factor and/or antiparietal cell antibodies. To evaluate the vitamin B12 status, we measured total plasma vitamin B12, plasma homocysteine, and plasma methylmalonic acid (pMMA) concentration and urinary methylmalonic acid-to-creatinine ratio. Participants were treated with oral cyanocobalamin at a dosage of 1000 μg/d throughout the study duration. Clinical and biological vitamin B12 deficiency related features were prospectively and systematically assessed over the 1-y study duration., Results: We included 26 patients with vitamin B12 deficiency revealing PA. Following 1 mo of oral vitamin B12 supplementation, 88.5% of patients were no longer deficient in vitamin B12, with significant improvement of plasma vitamin B12 [407 (297-485) compared with 148 (116-213) pmol/L; P < 0.0001], plasma homocysteine [13.5 (10.9-29.8) compared with 18.6 (13.7-46.8) μmol/L; P < 0.0001], and pMMA [0.24 (0.16-0.38) compared with 0.56 (0.28-1.09) pmol/L; P < 0.0001] concentrations than those at baseline. The enhancement of these biological parameters persisted throughout the 12-month follow-up, with no patients showing vitamin B12 deficiency by the end of the follow-up period. The median time to reverse initial vitamin B12 deficiency abnormalities ranged from 1 mo for hemolysis to 4 mo for mucosal symptoms., Conclusions: Oral supplementation with 1000 μg/d of cyanocobalamin has been shown to improve vitamin B12 deficiency in PA., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Objective: Neurologic problems are frequently described in infants with nutritional vitamin B12 (cobalamin) deficiency.Major neurologic consequences of infantile cobalamin deficiency include delays or regression in neurodevelopment and the occurrence of involuntary movements METHODS: We reviewed the medical records of infants with cobalamin deficiency and divided infants with involuntary movements into two groups as those, who developed involuntary movements during vitamin B12 supplementation (Group I) and those, who developed involuntary movements prior to supplementation therapy (Group II)., Results: We evaluated a total of 32 infants with the diagnosis of cobalamin deficiency. Involuntary movements were observed in 12 out of 32 infants. Group I and Group II consisted of 6 infants each. Of the infants with involuntary movements, five were exclusively breastfed until the time of diagnosis. The majority of infants in Group II had choreoathetoid movements; twitching and myoclonus in the face, tongue, and lips, and tremor in the upper extremities. These involuntary movements disappeared in one to three weeks after clonazepam therapy. In Group I; shaking movements, myoclonus, tremor, and twitching or protrusion were observed in patients' hands, feet, tongue, and lips on the 3rd-5th day of cobalamin supplementation. These involuntary movements disappeared within 5-12 days of clonazepam therapy., Conclusion: Recognition of nutritional cobalamin deficiency is important to perform a differential diagnosis of the condition from seizures or other causes of involuntary movements and avoid aggressive therapy and over treatment., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Vitamin B12 deficiency is commonly diagnosed using thresholds developed for adults, yet emerging evidence indicates these levels may not be appropriate for children and adolescents. This misalignment can lead to underdiagnosis in younger populations, with potential long-term health implications., Case Summary: Chief Complaint: The 17-year-old female patient experienced severe fatigue, menstrual irregularities, psychological distress, and neurological symptoms over several years. The 13-year-old male patient had behavioral changes, gastrointestinal complaints, and sensory disturbances from an early age.Diagnosis: Both adolescents displayed B12 levels that were considered low-normal based on adult thresholds, complicating their diagnostic processes. Their diverse and atypical symptomatology required a comprehensive review of their medical and family histories, clinical symptoms, and risk factors.Intervention: Treatment included administration of hydroxocobalamin injections, complemented by dietary adjustments.Outcome: Both patients responded well to the treatment, showing significant improvements in their symptoms and overall quality of life., Conclusion: The main takeaway from these cases is the importance of tailoring diagnostic adequate thresholds and treatment plans to the pediatric population to address and manage B12 deficiency effectively. This approach can significantly enhance patient outcomes and prevent the progression of potentially severe complications in later life., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Vitamin B12 deficiency is a critical medical condition that, if left untreated, can lead to severe symptoms and potentially serious and life-threatening complications. Clinical guidelines are designed to provide a standardized approach to diagnosis and treatment, aiming for consistency and effectiveness. However, it is well-established that not all patients fit into general guidelines., Objective: To investigate the clinical relevance of the submitted research to support these protocols for diagnosing and treating a B12 deficiency., Approach: Conducting a literature review of the references focused and used on diagnosing and treating vitamin B12 deficiency in adults and children., Results: No robust clinical trial nor RCT has been found to back up the current protocols. The research used is primarily based on assumptions rather than solid clinical evidence., Conclusion: Existing guidelines for vitamin B12 deficiency need to be significantly revised and improved through clinical research, clinical experience by experts in the field with input from patient groups worldwide., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: This systematic review and network meta-analysis aimed to evaluate the three different administration routes of vitamin B12: oral, intramuscular (IM), and sublingual (SL) routes., Methods: We searched four electronic databases (PubMed, Scopus, Web of Science, and Cochrane CENTRAL Register of Controlled Trials). We included only comparative studies. We performed a frequentist network meta-analysis to measure network estimates for the relative outcomes. Moreover, we conducted a pairwise meta-analysis using a random effect model to obtain direct estimates for outcomes. All outcomes were continuous, and the relative treatment effects were pooled as mean difference (MD) with 95% confidence intervals., Results: Thirteen studies were included in the meta-analysis, with a total of 4275 patients. Regarding increasing vitamin B12 levels, the IM route ranked first, followed by the SL route (MD = 94.09 and 43.31 pg/mL, respectively) compared to the oral route. However, these differences did not reach statistical significance owing to the limited number of studies. Regarding the hemoglobin level, the pooled effect sizes showed no difference between all routes of administration that could reach statistical significance. However, the top two ranked administration routes were the oral route (78.3) and the IM route (49.6)., Conclusion: All IM, oral, and SL routes of administration of vitamin B12 can effectively increase the level of vitamin B12 without significant differences between them, as thought previously. However, the IM route was the top-ranked statistically but without clinical significance. We found no significant difference among studied administrated routes in all other CBC parameters and homocysteine levels., (© 2024. The Author(s).)

This article is a commentary on the role of vitamin B 12 in age-related cognitive decline, with a meta-commentary on the misuse of the term "Alzheimer's Disease." The article describes the historical origins of the term "Alzheimer's Disease" and argues that the term should be restricted to a narrower segment of the age-related dementia spectrum. The article also outlines the role of vitamin B 12 in age-related cognitive decline and outlines the rationale for the treatment of B 12 deficiency to address a potentially reversible factor in cognitive decline., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: An increasing number of adult individuals are at risk of vitamin B12 deficiency, either from reduced nutritional intake or impaired gastrointestinal B12 absorption., Objective: This study aims to review the current best practices for the diagnosis and treatment of individuals with vitamin B12 deficiency., Methods: A narrative literature review of the diagnosis and treatment of vitamin B12 deficiency., Results: Prevention and early treatment of B12 deficiency is essential to avoid irreversible neurological consequences. Diagnosis is often difficult due to diverse symptoms, marked differences in diagnostic assays' performance and the unreliability of second-line biomarkers, including holo-transcobalamin, methylmalonic acid and total homocysteine. Reduced dietary intake of B12 requires oral supplementation. In B12 malabsorption, oral supplementation is likely insufficient, and parenteral (i.e. intramuscular) supplementation is preferred. There is no consensus on the optimal long-term management of B12 deficiency with intramuscular therapy. According to the British National Formulary guidelines, many individuals with B12 deficiency due to malabsorption can be managed with 1000 µg intramuscular hydroxocobalamin once every two months after the initial loading. Long-term B12 supplementation is effective and safe, but responses to treatment may vary considerably. Clinical and patient experience strongly suggests that up to 50% of individuals require individualized injection regimens with more frequent administration, ranging from daily or twice weekly to every 2-4 weeks, to remain symptom-free and maintain a normal quality of life. 'Titration' of injection frequency based on measuring biomarkers such as serum B12 or MMA should not be practiced. There is currently no evidence to support that oral/sublingual supplementation can safely and effectively replace injections., Conclusions: This study highlights the interindividual differences in symptomatology and treatment of people with B12 deficiency. Treatment follows an individualized approach, based on the cause of the deficiency, and tailored to help someone to become and remain symptom-free., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose of Review: Vitamin B 12 (B12, cobalamin) deficiency has been associated with neuropsychiatric symptoms, suggesting a role for B12 supplementation both as a treatment for psychiatric symptoms due to B12 deficiency and as an augmentation strategy for pharmacological treatments of psychiatric disorders. This critical review discusses the major causes of B12 deficiency, the range of psychiatric and non-psychiatric manifestations of B12 deficiency, the indications for testing B12 levels, and the evidence for B12 supplementation for major psychiatric disorders., Recent Findings: We find that high-quality evidence shows no benefit to routine B12 supplementation for mild depressive symptoms or to prevent depression. There is very limited evidence on the role of B12 supplementation to augment antidepressants. No high-quality evidence to date suggests a role for routine B12 supplementation in any other major psychiatric disorder. No formal guidelines indicate when clinicians should test B12 levels for common psychiatric symptoms, in the absence of major risk factors for deficiency or cardinal symptoms of deficiency. No robust evidence currently supports routine B12 supplementation for major psychiatric disorders. However, psychiatrists should be aware of the important risk factors for B12 deficiency and should be able to identify symptoms of B12 deficiency, which requires prompt testing, medical workup, and treatment. Testing for B12 deficiency should be considered for atypical or severe psychiatric presentations., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: In the 1940s to 1950s, high-dose folic acid supplements (>5 mg/d) were used clinically to reverse the megaloblastic anemia of vitamin B12 deficiency caused by pernicious anemia. However, this treatment strategy masked the underlying B12 deficiency and possibly exacerbated its neuropathological progression. The issue of masking and exacerbating B12 deficiency has recently been rekindled with the institution of folic acid fortification and the wide-spread use of folic acid supplements., Objectives: The objectives of this review are to describe clinical and epidemiological evidence that excess folic acid exacerbates B12 deficiency, to summarize a hypothesis to explain this phenomenon, and to provide guidance for clinicians., Results: Cognitive function test scores are lower and blood homocysteine and methylmalonic acid concentrations are higher in people with low B12 and elevated folate than in those with low B12 and nonelevated folate. High-dose folic acid supplementation in patients with pernicious anemia or epilepsy cause significant reductions in serum B12. It is hypothesized that high-dose folic acid supplements cause depletion of serum holotranscobalamin and thus exacerbate B12 deficiency., Conclusion: The evidence for excess folic acid exacerbating B12 deficiency is primarily correlative or from uncontrolled clinical observations, and the hypothesis to explain the phenomenon has not yet been tested. Nonetheless, the evidence is sufficiently compelling to warrant increased vigilance for identifying B12 deficiency in at risk individuals, including older adults and others with low B12 intake or conditions that are associated with B12 malabsorption, who also ingest excessive folic acid or are prescribed folic acid in high doses., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: JWM is co-author of a patent titled “Assay for Vitamin B12 Absorption and Method of Making Labeled Vitamin B12” (Patent Number: 8,202,507) issued to The Regents of the University of California (Oakland, CA), JWM is an associate editor for the journal Nutrition Reviews.

No international treatment standard for B12 deficiency exists. Current practice predominantly relies on more than 50 years old data. Consequently, this review investigates that we still recommend five injections with 1 mg B12 over 10 days followed by maintenance therapy with 1 mg oral B12 daily or injections, of which the interval is guided by symptom relief rather than normalization of biomarkers. Clinical studies are highly warranted and should include formulation and administration of B12. Subcutaneous self-injection may prove cost-effective and benefit an individualized treatment strategy., (Published under Open Access CC-BY-NC-BD 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/.)

Mutations in MMACHC cause cobalamin C disease (cblC, OMIM 277400), the commonest inborn error of vitamin B 12 metabolism. In cblC, deficient activation of cobalamin results in methylcobalamin and adenosylcobalamin deficiency, elevating methylmalonic acid (MMA) and total plasma homocysteine (tHcy). We retrospectively reviewed the medical files of seven cblC patients: three compound heterozygotes for the MMACHC (NM&#95;015506.3) missense variant c.158T>C p.(Leu53Pro) in trans with the common pathogenic mutation c.271dupA (p.(Arg91Lysfs*14), "compounds"), and four c.271dupA homozygotes ("homozygotes"). Compounds receiving hydroxocobalamin intramuscular injection monotherapy had age-appropriate psychomotor performance and normal ophthalmological examinations. In contrast, c.271dupA homozygotes showed marked psychomotor retardation, retinopathy and feeding problems despite penta-therapy (hydroxocobalamin, betaine, folinic acid, l-carnitine and acetylsalicylic acid). Pretreatment levels of plasma and urine MMA and tHcy were higher in c.271dupA homozygotes than in compounds. Under treatment, levels of the compounds approached or entered the reference range but not those of c.271dupA homozygotes (tHcy: compounds 9.8-32.9 μM, homozygotes 41.6-106.8 (normal (N) < 14); plasma MMA: compounds 0.14-0.81 μM, homozygotes, 10.4-61 (N < 0.4); urine MMA: compounds 1.75-48 mmol/mol creatinine, homozygotes 143-493 (N < 10)). Patient skin fibroblasts all had low cobalamin uptake, but this was milder in compound cells. Also, the distribution pattern of cobalamin species was qualitatively different between cells from compounds and from homozygotes. Compared to the classic cblC phenotype presented by c.271dupA homozygous patients, c.[158T>C];[271dupA] compounds had mild clinical and biochemical phenotypes and responded strikingly to hydroxocobalamin monotherapy., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: Determine comparative tolerance of daily oral and weekly parenteral cobalamin supplementation, in hypocobalaminaemic dogs with chronic enteropathy. Determine whether oral is as effective as parenteral supplementation at achieving eucobalaminaemia, in hypocobalaminaemic dogs with protein-losing enteropathy, severe hypocobalaminaemia or high canine inflammatory bowel disease activity index at inclusion., Materials and Methods: Thirty-seven client-owned dogs with hypocobalaminaemia and clinical signs of chronic enteropathy were prospectively enrolled in three UK referral centres. Dogs were randomly allocated to daily oral for 12 weeks or weekly parenteral cobalamin supplementation for 6 weeks and one additional dose 4 weeks later. Serum cobalamin, body condition score, canine inflammatory bowel disease activity index and bodyweight were assessed at inclusion, weeks 7 and 13. Serum methylmalonic acid concentration was evaluated at inclusion and at week 13. Owners completed treatment adherence, palatability, tolerance and satisfaction questionnaires at week 13., Results: Nineteen dogs completed the study. All dogs orally supplemented achieved normal or increased cobalaminaemia at weeks 7 and 13. There was no statistical difference in cobalamin concentration at week 13 in dogs treated with oral or parenteral supplementation, regardless of presence of protein-losing enteropathy, severity of hypocobalaminaemia or canine inflammatory bowel disease activity index at inclusion. Serum methylmalonic acid concentration was not significantly different between oral and parenteral groups, neither were treatment adherence, satisfaction, and tolerance scores at week 13., Clinical Significance: Oral is as effective and as well-tolerated as parenteral cobalamin supplementation in hypocobalaminaemic dogs with chronic enteropathy and severe clinical or biochemical phenotypes, and should be considered as a suitable treatment option regardless of disease severity., (© 2024 The Authors. Journal of Small Animal Practice published by John Wiley & Sons Ltd on behalf of British Small Animal Veterinary Association.)

Metformin is a cornerstone medication in the management of type 2 diabetes. Metformin is safe, effective, and inexpensive; however, it is associated with vitamin B12 deficiency. This study set out to evaluate the rate of vitamin B12 deficiency in Vietnamese patients with type 2 diabetes who were treated with metformin and to investigate factors associated with vitamin B12 deficiency. This is a cross-sectional study that was conducted in Vinmec Central Park Hospital from February to June 2023. The clinical and paraclinical characteristics of the participants were recorded, and the levels of vitamin B12 and folate were measured. The rate of vitamin B12 deficiency in patients treated with metformin was found to be 18.6%. Further, the duration of diabetes, duration of metformin use, metformin dose, and hemoglobin levels were statistically associated with vitamin B12 deficiency with OR (95% CI) = 1.12 (1.03-1.19), 1.01 (1.00-1.02), 1.002 (1.001-1.002), 0.74 (0.55-0.99), respectively. After adjusting for covariates, a metformin dose greater than the median dose remained the only parameter associated with vitamin B12 deficiency, with OR (95% CI) = 4.10 (1.62-10.36). Moreover, when combining both long-term use of metformin and a metformin dose greater than the median dose, the OR increased to 5.25 (95% CI: 2.11-13.15). These results demonstrate that vitamin B12 deficiency in patients treated with metformin is quite prevalent in Vietnam and that those with long-term use of metformin (48 months or more) and high metformin dose (1000 mg/day or more) are at high risk of experiencing this adverse effect and so require screening., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Huynh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., Competing Interests: The authors declare no competing interests., (Copyright: Gloria Lubega et al.)

Vitamin B12 (cobalamin) deficiency is common in patients with rheumatic diseases. Pernicious anemia is a well-known cause, but recent reports suggest that autoimmune-derived deficiency may not be limited to this cause alone. Symptoms of low vitamin B12 concentration are often deceptive, mimicking and overlapping with symptoms of other conditions. Neuropsychiatric manifestations, anemia, and fatigue are frequently attributed to a rheumatic disease without further evaluation. In this study, we present three cases of patients with neuropathic pain, depression, fatigue, and muscle weakness, initially attributed to a rheumatic disease, which almost completely resolved after implementing vitamin B12 supplementation. Furthermore, we provide an overview of current scientific reports regarding the potential use of cobalamin in rheumatology. Treatment of pain and neuropathy, often very challenging in long-lasting rheumatic diseases, can be more effective after a course of vitamin B12, even when no apparent deficiency is detected in laboratory tests. Considering recent research demonstrating vitamin B12's nerve-protecting properties, we recommend that physicians should assess vitamin B12 levels early in the diagnostic process of rheumatic diseases. In specific cases, physicians should consider cobalamin supplementation regardless of vitamin B12 serum concentration., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background & Aims: While vitamin B12 (B12) deficiency is considered as the hallmark of pernicious anemia (PA), iron deficiency (ID) is also prevalent. Indeed, this auto immune gastritis is responsible for parietal cell atrophy and increase in gastric pH, leading to impaired iron absorption. We compared PA patients' features according to their iron status at PA diagnosis, and we assessed the iron status recovery after oral or intravenous iron supplementation., Methods: We prospectively included patients presenting with a newly diagnosed PA in a tertiary referral hospital between November 2018 and October 2020. Iron status was assessed at PA diagnosis then regularly during a standardized follow-up. In case of ID, the decision of treatment with oral and/or intravenous iron supplementation was left to the clinician convenience., Results: We included 28 patients with newly diagnosed PA. ID was observed in 21/28 (75.0%) patients: from the PA diagnosis in 13 patients, or during the follow-up in 8 patients. Iron deficient PA patients had higher plasma B12 (p = 0.04) and lower homocysteine levels (p = 0.04). Also, ID was independently associated with the 'APCA (anti-parietal cell antibodies) alone' immunological status (absence of anti-intrinsic factor antibodies) after adjustment for age, gender and B12 level (aOR 12.1 [1.1-141.8], p = 0.04). High level of APCA was associated with lower ferritin level. After 3 months of supplementation, 3/11 PA patients normalized the iron status with oral iron supplementation, versus 7/8 with intravenous iron supplementation (p = 0.02)., Conclusion: The high frequency of iron deficiency in PA highlights the interest of regular assessment of iron status in this condition. ID was associated with a profile including APCA alone and less pronounced B12 deficiency. Intravenous iron supplementation seemed to be more efficient than an oral supplementation in these preliminary data., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: The recreational use of nitrous oxide (N 2 O) has gained popularity over recent years. We present a case series of excessive N 2 O users with neurological complications., Methods: In this retrospective three-centre study, we used a text mining algorithm to search for patients who used N 2 O recreationally and visited a neurologist., Results: We identified 251 patients. The median duration of N 2 O use was 11 months (interquartile range [IQR], 3-24) and the median amount of N 2 O used per occasion 1.6 kg (IQR 0.5-4.0). Clinically, polyneuropathy (78%), myelopathy (41%), and encephalopathy (14%) were the most common diagnoses. An absolute vitamin B12 deficiency of < 150 pmol/L was found in 40% of cases. In 90%, at least one indicator of functional vitamin B12 status (vitamin B12, homocysteine, or methylmalonic acid) was abnormal. MRI showed signs of myelopathy in 30/55 (55%) of cases. In 28/44 (64%) of those who underwent electromyography, evidence of axonal polyneuropathy was found. Most (83%) patients were treated with vitamin B12 supplementation, and 23% were admitted to the hospital. Only 41% had follow-up for ≥ 30 days, and 79% of those showed partial or complete recovery., Conclusions: In this case series of excessive N 2 O users, we describe a high prevalence of polyneuropathy, myelopathy, and encephalopathy. Stepwise testing for serum levels of vitamin B12, homocysteine, and methylmalonic acid may support the clinical diagnosis. Due to low sensitivity, MRI of the spinal cord and electromyography have limited value. Effective treatment should incorporate supplementation of vitamin B12 and strategies to prevent relapses in N 2 O use., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Subacute combined degeneration (SCD) of the spinal cord is a disease involving the lateral and posterior columns of the spinal cord that can manifest in patients with vitamin B12 deficiency. Nitrous oxide (N2O)-induced SCD of the spinal cord is a result of N2O interfering with the metabolism of vitamin B12 and results in nervous system demyelination. This is an infrequent complication of N2O anesthesia; however, cases are rising with recreational N2O use. This case report describes a patient with SCD of the spinal cord induced by recreational N2O abuse. The patient presented to a spine surgery clinic with a 3-week history of progressive global weakness and paresthesias. After a detailed history and physical examination, the diagnosis was made and supported by various tests and imaging findings. Despite marked neurologic deficits, the patient's symptoms improved markedly with therapy and vitamin B12 supplementation. Spine surgery clinicians may be confronted with these cases and should be aware of this atypical presentation of SCD. As in our case, patients may present with neurologic deficits of unclear etiology. Neurologic dysfunction may be irreversible; therefore, accurate diagnosis, medical treatment, and complete neurologic evaluation are of the utmost importance to prevent additional progression., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

Background: Diarrhoea is defined as stool frequency of more than three times in twenty-four hours or a stool weight of more than two hundred grams and it is labelled as chronic diarrhoea if it persists for more than four weeks. Chronic diarrhoea is a common gastrointestinal problem worldwide that affects three to fifteen percent of population. Objective was to determine the efficacy of vitamin B 12 replacement in treatment of chronic diarrhoea in vitamin B deficient patients. It was a Quasi-experimental study carried out at Pakistan Ordinance Factory (POF) Hospital Wah Cantt, from September 2023 to February 2024., Methods: All the new patients of chronic diarrhoea of ages between 12-65 years who had low serum vitamin B 12 and normal serum folate levels were included in the study. The patients were booked from Medicine and Allied outpatient and they were given parenteral vitamin B12. The sub-set of patients in whom diarrhoea was settled was followed up till six months. The efficacy was defined as settlement of diarrhoea with parenteral vitamin B12 within one week. The secondary outcomes were adequacy of serum vitamin B12 levels at 2 weeks, three months and six months after treatment. All patients (100%) had adequate B12 levels till follow up. Data was analyzed through SPSS., Results: Efficacy of parenteral B12 supplementation was seen in 16 (76.2%) patients. Out of sixteen patients who responded to vitamin B12 supplementation, 10 (47.6%) patients showed improvement in less than two days, 5 (23.8%) showed improvement in less than four days and 1 (4.8) patient stopped experiencing diarrhoea within seven days of intramuscular vitamin B12 with p-value of <0.001., Conclusions: Replacement of vitamin B 12 in patients with chronic diarrhoea having low vitamin B 12 results in settlement of diarrhoea.

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.

Pooled data from published reports on infants with clinically diagnosed vitamin B12 (B12) deficiency were analyzed with the purpose of describing the presentation, diagnostic approaches, and risk factors for the condition to inform prevention strategies. An electronic (PubMed database) and manual literature search following the PRISMA approach was conducted (preregistration with the Open Science Framework, accessed on 15 February 2023). Data were described and analyzed using correlation analyses, Chi-square tests, ANOVAs, and regression analyses, and 102 publications (292 cases) were analyzed. The mean age at first symptoms (anemia, various neurological symptoms) was four months; the mean time to diagnosis was 2.6 months. Maternal B12 at diagnosis, exclusive breastfeeding, and a maternal diet low in B12 predicted infant B12, methylmalonic acid, and total homocysteine. Infant B12 deficiency is still not easily diagnosed. Methylmalonic acid and total homocysteine are useful diagnostic parameters in addition to B12 levels. Since maternal B12 status predicts infant B12 status, it would probably be advantageous to target women in early pregnancy or even preconceptionally to prevent infant B12 deficiency, rather than to rely on newborn screening that often does not reliably identify high-risk children.

Objective: To evaluate the efficacy and safety of sublingual methylcobalamin for the treatment of vitamin B12 deficiency anemia in children., Methods: A single arm intervention study was conducted between November, 2020 and April, 2022 in children aged 1-12 years with vitamin B12 deficiency anemia. Children aged 1-6 years received a tablet of methylcobalamin (1500 mcg) by sublingual route every alternate day (three doses) while those aged 7-12 years received five such doses. Thereafter, one such sublingual tablet was given weekly and all participants were followed-up for 6 weeks., Results: 37 children with a mean (SD) age of 8.2 (4.1) years were treated and followed up prospectively. On day 10, no child needed rescue therapy with parenteral methylcobalamin. After 6 weeks, the mean (SD) serum cobalamin (mL) increased from 123.3 (35.5) pg/mL to 507.3 (274.2) pg/mL (P<0.001), plasma homocysteine (L) decreased from 48.9 (17.8) pg/mL to 16.3 (8.5) µmol/L (P<0.001), the mean (SD) hemoglobin increased by 2.3 (1.1) g/dL (P<0.001), and MCV decreased by 12.9 (6.8) fL (P<0.001). 67.6% children persisted to have anemia, albeit majority of them had mild or moderate anemia. There were no unsolicited side-effect reported., Conclusion: Sublingual methylcobalamin is effective for the treatment of vitamin B12 deficiency anemia in children; although, the duration of treatment needs to be longer than six weeks.

In early-onset (EO) cblC deficiency (MMACHC), hydroxocobalamin dose-intensification (OHCBL-DI) improved biochemical and clinical outcome. In mammals, Cobalamin is reduced, in a reaction mediated by MMACHC. Pathogenic variants in MMACHC disrupt the synthesis pathway of methyl-cobalamin (MetCbl) and 5'-deoxy-adenosyl-cobalamin (AdoCbl), cofactors for both methionine synthase (MS) and methyl-malonyl-CoA mutase (MCM) enzymes. In 5 patients (pts.), with EO cblC deficiency, biochemical and clinical responses were studied following OHCbl-DI (mean ± SD 6,5 ± 3,3 mg/kg/day), given early, before age 5 months (pts. 1, 2, 3 and 4) or lately, at age 5 years (pt. 5). In all pts., total homocysteine (tHcy), methyl-malonic acid (MMA) and Cob(III)alamin levels were measured. Follow-up was performed during 7 4/12 years (pts. 1, 2, 3), 3 3/12 years (pt. 4) and 3 4/12 years (pt. 5). OHCbl was delivered intravenously or subcutaneously. Mean ± SD serum Cob(III)alamin levels were 42,2 × 10 6  ± 28, 0 × 10 6  pg/ml (normal: 200-900 pg/ml). In all pts., biomarkers were well controlled. All pts., except pt. 5, who had poor vision, had central vision, mild to moderate nystagmus, and with peri-foveolar irregularity in pts. 1, 2 and 4, yet none had the classic bulls' eye maculopathy and retinal degeneration characteristic of pts. with EO cblC deficiency. Only pt. 5, had severe cognitive deficiency. Both visual and cognitive functions were better preserved with early than with late OHCBL-DI. OHCBL-DI is suggested to bypass MMACHC, subsequently to be rescued by methionine synthase reductase (MSR) and adenosyl-transferase (ATR) to obtain Cob(I)alamin resulting in improved cognitive and retinal function in pts. with EO cblC deficiency., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Vitamin B12 is inextricably associated with the development and maintenance of neuronal functions. It is classically associated with subacute combined degeneration and peripheral neuropathy; however, cranial neuropathy is uncommon. We observed the rarest neurological manifestation of B12 deficiency. A 12 months infant had history of lethargy, irritability, anorexia, paleness, vomiting, and neurodevelopmental delay for 2 months. He also developed inattention and altered sleep pattern. His mother noticed bilateral inward rotation of both eyes. On examination, the infant had bilateral lateral rectus palsy. The infant was found to have anemia (7.7g/dL) and severe B12 deficiency (74pg/mL). On MRI, there was cerebral atrophy, subdural hematoma (SDH) and wide cisternal spaces and sulci. On supplementation with cobalamin, he improved clinically though mild restriction of lateral gaze on the left side persists. Follow up MRI showed significant improvement in cerebral atrophy with resolution of SDH. To date, such clinical presentation of B12 deficiency has never been reported. The authors suggest B12 supplementation for at risk population esp at antenatal stage and lactating mothers in national programs. The treatment of this condition should be initiated early to prevent long term sequelae., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To compare the mean Likert (caregiver impression of change) and CAPUTE scores in children with ITS treated with daily injectable vitamin B12 alone versus injectable vitamin B12 with other multinutrients at 1 wk and 1 mo of therapy., Methods: This was an open-label, active-controlled, assessor-blinded, noninferiority, randomized clinical trial. The participants included children aged 3 mo to 2 y with infantile tremor syndrome. Children were randomized to receive either 1 mg of daily injectable vitamin B12 or 1 mg of daily injectable vitamin B12 with other multinutrients (B12 + MV). Primary outcome measure was the mean Likert score in the two arms at 1 wk. Secondary outcome measures were mean change in CAPUTE scores at 1 wk of therapy; and mean change in CAPUTE and Vineland Social Maturity Scale (VSMS) scores after 1 mo of treatment., Results: Seventy-two (N = 72) of the 160 screened were enrolled and randomized. The mean (SD) Likert score in the B12 group (n = 38) was 16.1 (3.7) and in the B12 + MV group (n = 34) was 14.9 (3.7); p = 0.237. Mean (SD) change in CAPUTE (CAT/CLAMS) at 1 mo in the groups was not statistically different. The mean (SD) change in social quotient in the B12 monotherapy group, 35.0 (20.7) was significantly higher than the B12 + multinutrient group 23.5 (15.4); p=0.01., Conclusion: Injectable vitamin B12 monotherapy in ITS resulted in an improvement that was noninferior to combination multinutrient therapy, strongly supporting vitamin B12 deficiency as the cause of infantile tremor syndrome., Trial Registration: The trial was registered at CTRI.org (CTRI/2018/05/013841)., (© 2022. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Development of epileptic spasms in infants with vitamin B 12 deficiency is uncommon. In some cases, infants presenting with epileptic spasms have been found to have concurrent vitamin B 12 deficiency. Treatment with vitamin B 12 and adrenocorticotropic hormone (ACTH) resulted in resolution of epileptic spasms. In others, epileptic spasms have developed during recovery from vitamin B 12 deficiency. Treatment with ACTH or other seizure medications resulted in resolution of epileptic spasms, although response has been less predictable. We describe three infants who initially presented with clinical and laboratory features of vitamin B 12 deficiency. Treatment with vitamin B 12 resulted in rapid resolution of symptoms. However, recovery was interrupted by the development of epileptic spasms. All infants showed hypsarrhythmia on electroencephalography. Treatment with prednisolone, with or without other antiseizure medications, resulted in slow resolution of spasms. Cognitive and language delays were noted in two infants. Epileptic spasms may supervene during recovery from vitamin B 12 deficiency affecting outcomes., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Ischemic stroke is the most prevalent form of stroke and has a high incidence in older adults, characterized by high morbidity, mortality, disability, and recurrence rate. Vitamin B 12 deficiency is prevalent in the elderly and has been reported to be associated with ischemic stroke. The mechanisms maybe include the disorder of methylation metabolism, accumulation of toxic metabolites, immune dysfunction, affecting gut microbial composition and gut-brain immune homeostasis, and toxic stress responses to the brain. Vitamin B 12 deficiency may lead to cerebral artery atherosclerosis, change myelination, influence the metabolism and transmission between nerve tissue, and ultimately causes the occurrence and development of ischemic stroke. This paper reviews the correlation between vitamin B 12 deficiency and ischemic stroke, looking forward to improving clinicians' understanding and providing new therapeutic directions for ischemic stroke., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Introduction: Nutritional vitamin B12 deficiency has been shown to cause Infantile epileptic spasms syndrome (IESS) in infants in anecdotal studies., Methods: In this retrospective cohort study, we intended to study the clinical presentation, neurophysiological, laboratory abnormalities, treatment, and neurodevelopmental outcome at 6-months in infants presenting with IESS secondary to nutritional vitamin B12 deficiency (NVBD) and to compare these variables from the rest of the infants with IESS without vitamin B12 deficiency. We included only spasm-free cases or those who showed at least a 50% reduction in spasm frequency on D7 after starting oral/parenteral vitamin B12. We used well-validated measurement tools like the Developmental Assessment Scale for Indian Infants (DASII), Child Feeding Index (CFI), Burden of amplitudes and epileptiform discharges (BASED) score, countable Hypsarrhythmia paroxysm index (cHPI), durational Hypsarrhythmia paroxysm index (dHPI), and Early childhood epilepsy severity scale (E-CHESS) score for documenting these variables., Results: Data from 162 infants with IESS (21 caused by NVBD) were included in our study. The NVBD group had more patients residing in the rural region, with lower socioeconomic status, vegetarian mothers and poor complementary feeding index (p<0.001 for all). The NVBD group also had less number of patients requiring antiseizure medications (ASMs) and hormonal therapy(p<0.001), remained seizure free at six months (p=0.008), lower number of clusters per day (p=0.02) and the number of spasms per clusters at presentation (p=0.03), lower BASED score (p=0.03) and cHPI, dHPI at presentation (p<0.001). All of them remained spasm-free, with normal electroencephalogram at 6-months. Development quotient at baseline, at 6-months, and improvement in development quotient between these two-time points were more in the vitamin B12 deficiency group (p<0.001). All of them had clinical features of pre-ITS (infantile tremor syndrome) or ITS and it was found to be the only independent predictor of NVBD in infants with IESS. Mothers of all these infants had low serum vitamin B12 levels (<200 pg/ml)., Conclusions: Nutritional vitamin B12 deficiency may cause IESS in infants. Hence, vitamin B12 deficiency needs to be ruled out in patients with IESS without any definite etiology., Competing Interests: Declaration of Competing Interest None, (Copyright © 2023 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

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 < 6.7 mg/dL. As IgA deficiency is associated with an increased risk of celiac disease, the patient underwent upper and lower endoscopy, which was grossly unremarkable; however, histology revealed a pattern consistent with autoimmune gastritis. Subsequent serum evaluation was remarkable for an elevated fasting gastrin level and an elevated parietal cell antibody level without macrocytic anemia, iron deficiency, or vitamin B12 depletion. The patient was diagnosed with autoimmune gastritis (AIG) and subsequently initiated on parenteral B12 supplementation therapy with improvement in her neurologic and gastrointestinal symptoms., Conclusion: This case illustrates the importance of recognition of red flag findings in a patient with known autoimmune disease. Following well-established health maintenance recommendations for individuals with T1DM ensures that common comorbidities will be detected. Autoimmune gastritis, while a rarer pathology in the pediatric population, deserves consideration in patients with pre-existing autoimmune conditions and new gastrointestinal or neurologic symptoms, as AIG can be associated with poor outcomes and risk of malignancy. Initial lab findings associated with an eventual diagnosis of AIG typically include anemia, iron deficiency, or Vitamin B12 deficiency. However, as demonstrated in this case, symptoms of AIG can rarely present before anemia or Vitamin B12 deficiency develops. To prevent permanent neurological damage, parenteral Vitamin B12 therapy must be considered even in the absence of Vitamin B12 deficiency, especially in those patients already experiencing neurological symptoms., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Vitamin B12 plays a key role in DNA stability. Research indicates that vitamin B12 deficiency leads to indirect DNA damage, and vitamin B12 supplementation may reverse this effect. Vitamin B12 acts as a cofactor for enzymes such as methionine synthase and methylmalonyl-CoA mutase, which are involved in DNA methylation and nucleotide synthesis. These processes are essential for DNA replication and transcription, and any impairment can result in genetic instability. In addition, vitamin B12 has antioxidant properties that help protect DNA from damage caused by reactive oxygen species. This protection is achieved by scavenging free radicals and reducing oxidative stress. In addition to their protective functions, cobalamins can also generate DNA-damaging radicals in vitro that can be useful in scientific research. Research is also being conducted on the use of vitamin B12 in medicine as vectors for xenobiotics. In summary, vitamin B12 is an essential micronutrient that plays a vital role in DNA stability. It acts as a cofactor for enzymes involved in the synthesis of nucleotides, has antioxidant properties and has potential value as a generator of DNA-damaging radicals and drug transporters.

Objective: To evaluate the efficiency of the sublingual route for the treatment of vitamin B12 deficiency in infants. Background: Vitamin B12 deficiency is common in children. In breastfed infants, the main reason is maternal B12 deficiency. Parenteral administration is commonly prescribed. However, patient compliance is not satisfactory due to repeated painful parenteral applications. It is also known that the oral route is efficient in high doses. In recent years, the sublingual route has been tried. This route stands out due to its easy applicability and low cost. However, there are few efficacy studies in infants for the sublingual route. Materials and methods: The study included 49 infants aged 6-12 months. All infants with marginal or deficient B12 levels (<300 pg/mL) were incidentally detected and treated with sublingual methylcobalamin. Each dose was 1000 μg and administered once a day in the first week, every other day in the second week, twice a week in the third week, and once a week in the last week. Serum vitamin B12 levels were measured before and after the treatment. Paired Sample T-Test was used to compare variables. Results: All infants had normal physical development and had no hematological or neurological issues. It was learned from the parents that the infants tolerated treatment well, and no side effects related to the treatment, such as vomiting or rash, were observed. Before and after the treatment, the mean vitamin B12 levels were 199±57 pg/mL and 684±336 pg/ml, respectively. The difference between the means was statistically significant (p<0.001). Conclusion: According to the study, it seems possible to treat vitamin B12 deficiency via a sublingual route in infants. In addition, methylcobalamin can be an alternative to the commonly used cyanocobalamin.

Introduction: MetforminHydrochloride is an antidiabetic used for many years, currently; it considered the first choice in treatment of type 2 diabetes (T2D). It decreases insulin resistance, does not induce hypoglycaemia, increases glucose utilization in the liver and skeletal muscle, and decreases hepatic glucose production. Its adverse effects (AE) are gastrointestinal, decrease in vitamin B12 absorption, abnormalities of hemogram and rarely skin reactions. The objective of this study was to report the type and frequency of AEs of Metformin Hydrochloride used in the therapeutic management of T2D patients admitted to the medical center and the diabetes home of Sidi Bel-Abbès in Algeria., Materials and Methods: A cross-sectional descriptive study was carried out over a period of four months, from January 1st, 2017 to April 30th, 2017, involving 130 patients treated with Metformin Hydrochloride consulting at Mimoun City Diabetes Home and Gambetta Diabetes Center in the town of Sidi Bel-Abbès. The primary outcome measure was the determination of the type and frequency of AEs related to normal dosages or overdose use of Metformin Hydrochloride in T2D. Data were collected from patient records, using a questionnaire, and analyzed using Statistical Package for the Social Sciences, version 20 software., Results: 130 patients were included, including 82 women, with a mean age of 51.08±8.85 years (30-66). One hundred and ninety-eight (198) AEs were reported, an average of 1.52 AEs per patient. Among them, 95 (47.98%) AEs are digestive disorders (30.77% of patients suffered from diarrhea, 10.77% had nausea and vomiting, 8.46% suffered from abdominal pain and bloating, 3.85% lost their taste, 7.69% complained of epigastric cramps and 11.54% of anorexia), 29 (14.65%) AEs are hypoglycaemia, 73 (36.87%) AEs are other symptoms and 1 (0.50%) EI is vitamin B12 deficiency and no cases of lactic acidosis or allergic reaction were reported. Five (3.85%) patients had a total and lasting intolerance to Metformin Hydrochloride leading to its discontinuation following persistent diarrhoea., Conclusion: AEs of Metformin Hydrochloride used in the management of T2D patients consulting at the medical center and the Diabetes home of Sidi Bel-Abbès are frequent. Digestive disorders were the most frequent, diarrhea was very frequent and led to discontinuation of treatment in 3.85% of T2D patients, followed by nausea and vomiting, then abdominal pain, bloating and epigastric cramps, and rarely taste metallic. Hypoglycaemia was frequent following its association with insulin, the onset of headaches and fatigue were frequent, but no case of lactic acidosis or allergic reaction was reported. Due to a lack of means, the dosage of homocysteine and methylmalonic acid had not been carried out to confirm the vitamin B12 deficiency in the patient whose level was less than 200ng/mL. A precise assessment of the imputability of reported AEs is necessary., (Copyright © 2022 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Vitamin B12 deficiency is common in Ireland, The Irish Longitudinal Study on Aging (TILDA) survey indicates 12% of over 50s in Ireland are low or deficient. The condition is commonly managed exclusively in general practice., Aim: The intention of this audit was to establish whether B12 deficiency is diagnosed correctly and whether there was over-treatment of patients., Methods: The audit was conducted in an urban general practice in midwest Ireland. The primary limitation was the low number of patients. Thirty-five patients were included after practice database searches. An initial audit was performed which compared with the standard, Royal University of Bath: 'Guidelines for the Investigation & Management of B12 deficiency'., Results: The recommendations from this audit were to complete follow-on investigations and to switch over patients from IM to oral replacement. Twenty-one patients were then recalled, and investigations were performed. Ten patients were then switched from IM replacement to oral therapy. A re-audit was then completed. The re-audit showed marked improvement in compliance, from 17% (n = 6) to 83% (n = 29). The reduction in patients on IM therapy will decrease practice burden, with an annual reduction of nurse consultations by 46, representing a 30% decrease in nurse consultations for IM vitamin B12. This equates to an annual cost reduction of €1,340., Conclusion: This closed loop audit demonstrated that there was over treatment and under investigation of patients with B12 deficiency in general practice and that auditing of this process could both reduce risk for patients and save money and time., (© 2022. The Author(s).)

Background: Vitamin B 12 (VB12) deficiency is a well-described complication post-gastrectomy. It is caused by the loss of parietal cell mass leading to megaloblastic anaemia. This closed-loop audit assesses patient understanding of and adherence with VB12 supplementation guidelines post-gastrectomy., Methods: A closed-loop audit cycle was performed. After the first cycle, an educational intervention was actioned prior to re-audit. One hundred twenty-five patients who underwent gastrectomy between 2010 and 2020 were available for study (86 total gastrectomies (TG), 39 subtotal gastrectomies (STG)). Twenty-nine patients who had not been adherent with VB12 supplementation/surveillance were eligible for re-audit., Results: 91.9% (79/86) of TG patients reported adherence in regular parenteral VB12 supplementation. Adherence was significantly lower for STG for checking (and/or replacing) their VB12, with only 53.8% (21/39) checking their VB12 levels. 67/125 (53.6%) of the patients stated that they knew it was important to supplement B 12 post-gastrectomy. 37.8% (43/113) of participants could explain why this was important, and 14.4% (18/125) had any knowledge of the complications of VB12 deficiency. Following re-audit, 5/8 (57.5%) of TG patients who had not been adherent with VB12 supplementation in the first cycle were now adherent with VB12 supplementation following our educational intervention. 7/17 (41.2%) of the STG group had received VB12 or made arrangements to receive supplemental VB12 if it was indicated., Conclusion: This study demonstrates good adherence in those undergoing TG. Patient understanding correlates with adherence, suggesting that patient education and knowledge reinforcement may be key to adherence with VB12 supplementation. A simple educational intervention can improve adherence with VB12 supplementation in patients undergoing gastrectomy., (© 2022. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)