Vitamin B12 responsive developmental and epileptic encephalopathy due to a novel mutation in the FUT2 gene: a case report.

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.

A cyanide-free sample preparation methodology prior to determination of vitamin B12 in infant milk formula using hydrophilic interaction liquid chromatography with fluorescence detection.

The analysis of vitamin B12 in infant formulas typically requires the use of cyanide during sample preparation to convert the unstable vitamers (hydroxocobalamin, methylcobalamin and adenosylcobalamin) to cyanocobalamin, the most stable form of vitamin B12. To eliminate the risk to laboratory analysts in handling cyanide, alternative strategies are preferred for the analysis of vitamin B12. This research demonstrates the use of cobalamin-derived α-ribazole (a nucleoside moiety of vitamin B12) to determine total vitamin B12 content. Infant formula samples underwent protein denaturation and sugar removal with subsequent acidic hydrolysis and dephosphorylation employed to release α-ribazole, which was isolated by boronate affinity chromatography then analysed by hydrophilic interaction liquid chromatography with fluorescence detection. The method was validated using bovine- and ovine milk-based infant formula samples. The newly developed method was linear over the range of 0.65-6.48 ng mL-1 with repeatability of 3.78-5.47% relative standard deviation (RSDr, n = 10) and an intermediate precision of 3.59-10.0% RSDiR (n = 10). The limits of detection and quantitation (LOD and LOQ) were 0.4 and 1.2 µg 100 g-1 of dry weight, respectively. Accuracy was 68.9-76.4% and 68.7-80.0% at 50 and 150% of typical B12 concentrations in infant formula, respectively. The validated method was applied to eleven infant formulas and no statistical difference (p = 0.45, α = 0.05) was found when comparing with the results obtained using the AOAC Official Method 2014.02 high performance liquid chromatography with ultraviolet detection that requires the use of cyanide. These results indicate that the newly validated method is not only reliable but also offers a safer alternative for routine vitamin B12 determination in infant formula while maintaining high accuracy and precision.

Taurine/chenodeoxycholic acid ratio as a potential serum biomarker for low vitamin B12 levels in humans.

Deficiency of vitamin B12 (B12 or cobalamin), an essential water-soluble vitamin, leads to neurological damage, which can be irreversible and anaemia, and is sometimes associated with chronic disorders such as osteoporosis and cardiovascular diseases. Clinical tests to detect B12 deficiency lack specificity and sensitivity. Delays in detecting B12 deficiency pose a major threat because the progressive decline in organ functions may go unnoticed until the damage is advanced or irreversible. Here, using targeted unbiased metabolomic profiling in the sera of subjects with low B12 levels v control individuals, we set out to identify biomarker(s) of B12 insufficiency. Metabolomic profiling identified seventy-seven metabolites, and partial least squares discriminant analysis and hierarchical clustering analysis showed a differential abundance of taurine, xanthine, hypoxanthine, chenodeoxycholic acid, neopterin and glycocholic acid in subjects with low B12 levels. Random forest multivariate analysis identified a taurine/chenodeoxycholic acid ratio, with an AUC score of 1, to be the best biomarker to predict low B12 levels. Mechanistic studies using a mouse model of B12 deficiency showed that B12 deficiency reshaped the transcriptomic and metabolomic landscape of the cell, identifying a downregulation of methionine, taurine, urea cycle and nucleotide metabolism and an upregulation of Krebs cycle. Thus, we propose taurine/chenodeoxycholic acid ratio in serum as a potential biomarker of low B12 levels in humans and elucidate using a mouse model of cellular metabolic pathways regulated by B12 deficiency.

Pyridoxal-5'-phosphate: A cost-effective treatment candidate for hypertensive patients?

OBJECTIVES: Because angiotensin (Ang) II is an essential vasoconstrictive peptide, we analyzed the impact of its post-translational modification to pyruvamide-Ang II (Ang P) by pyridoxal-5'-phosphate (PLP) on blood pressure. PLP is a less expensive vitamin B6 derivative and, therefore, could be a cost-effective drug against hypertension. METHODS: Effect of Ang P on calcium ion entry into vascular smooth muscle cells (VSMCs) was analyzed. Binding affinity of Ang P to angiotensin II type 1 receptor (AT1R) was measured. Vasoconstrictive effect of Ang P was investigated using the bioassay of isolated perfused rat kidneys. Spontaneously hypertensive rats (SHR) were administered PLP. Additionally, Wistar Kyoto rats (WKY) received Ang II and PLP. Blood pressure was measured time-dependently. RESULTS: Ang II, incubated with PLP, was post-translationally modified to Ang P. Calcium ion entry in VSMCs was significantly lower with Ang P compared to Ang II. Binding affinity of Ang P to AT1R was lower compared to Ang II. Perfusion pressure of isolated perfused rat kidneys increased less by Ang P than by Ang II. Blood pressure of SHR treated with PLP decreased significantly. Blood pressure of WKY rats treated with Ang II was increased to hypertensive values, whereas blood pressure of WKY rats cotreated with Ang II and PLP was not. CONCLUSION: PLP induces a post-translational modification of Ang II decreasing blood pressure in rats. Assuming that increased PLP intake in the form of vitamin B6 might reduce blood pressure in hypertensive patients, PLP might be a cost-effective drug against hypertension.

Crystal structure of l-threonine-O-3-phosphate decarboxylase CobC from Sinorhizobium meliloti involved in vitamin B12 biosynthesis.

Vitamin B12 is involved in many important biochemical reactions for humans, and its deficiency can lead to serious diseases. The industrial production of vitamin B12 is achieved through microbial fermentation. In this work, we determine the crystal structures of the l-threonine-O-3-phosphate (Thr-P) decarboxylase CobC from Sinorhizobium meliloti (SmCobC), an industrial vitamin B12-producing bacterium, in apo form and in complex with a reaction intermediate. Our structures supported the Thr-P decarboxylase activity of SmCobC and revealed that the positively charged substrate-binding pocket between the large and small domains determines its substrate selectivity for Thr-P. Moreover, our results provided evidence for the proposition that the AP-P linker is formed by direct incorporation of AP-P in the biosynthetic pathway of vitamin B12 in S.meliloti.

Se-incorporated polycaprolactone spherical polyhedron enhanced vitamin B2 loading and prolonged release for potential application in proliferative skin disorders.

Development of novel drug vehicles for vitamin B2 (VitB2) delivery is very important for designing controllable release system to improve epidermal growth and bone metabolism. In this work, selenium (Se)-incorporated polycaprolactone (PCL) spherical polyhedrons are successfully synthesized via a single emulsion solvent evaporation method which is utilized to load VitB2 to fabricate cell-responsive Se-PCL@VitB2 delivery systems. Their physicochemical properties are characterized by DLS, SEM, XRD, FTIR, and TGA-DSC. The release kinetics of VitB2 or Se from the samples are investigated in PBS solution (pH = 2.0, 5.0, 7.4, 8.0 and 12.0). The cytocompatibilities are also evaluated with normal BMSC and epidermal HaCat cells. Results exhibit that Se-PCL@VitB2 particles presents spherical polyhedral morphology (approximately (3.25 ±â€¯0.46) µm), negative surface charge (-(54.03 ±â€¯2.94) mV), reduced crystallinity and good degradability. Stability experiments imply that both VitB2 and Se might be uniformly dispersed in PCL matrix. And the incorporation of Se facilely promotes the loading of VitB2. The encapsulation efficiency and loading capacity are (98.42 ±â€¯1.06)% and (76.25 ±â€¯1.27) for Se-PCL@VitB2 sample. Importantly, it exhibits more prolonged release of both VitB2 and Se in neutral PBS solution (pH = 7.4) than other pH conditions. Presumably, the electrostatic interaction between Se, VitB2 and PCL contribute to its release mode. Cell experiments show that Se-PCL@VitB2 presents strong cytotoxicity to HaCat cells mainly due to the cytotoxic effect of Se anions and PCL degradation products. However, it exhibits weak inhibitory effect on BMSC cells. These note that the synthesized Se-PCL@VitB2 particles can be promising drug vehicles for potential application in epidermal proliferative disorders.

The Association Between Vitamin B12 Deficiency and Diabetic Foot Ulcer in Type 2 Diabetic Patients in Qassim Province, Saudi Arabia: A Case-Control Study.

Background Diabetic foot ulcer (DFU) is a major complication of diabetes with many identified risk factors. These include poor control of diabetes, cardiovascular disease, smoking, and end-stage kidney disease. This study aims to shed light on the micronutrient status of diabetic patients and its effect on DFU, particularly, the association between vitamin B12 deficiency and DFU. Methodology This retrospective case-control study included adults in Buraydah who were at least 18 years old and had type 2 diabetes mellitus. Data were obtained from the electronic files of the patients who visited the diabetes center from January 2018 to August 2023 and were analyzed using SPSS version 27.0.1 (IBM Corp., Armonk, NY, USA). Results The research involved 221 participants, with 114 controls (individuals with diabetes but no DFU), and 107 cases (individuals with diabetes affected by DFU). Vitamin B12 levels varied, with 79.2% falling within the normal range of 187-883 pg/mL. The average age of cases (58.5 years, SD = 11.3) was notably higher than that of controls (54.1 years, SD = 14.1). Glycated hemoglobin levels were significantly higher in cases (8.7, SD = 2.0) compared to controls (7.6, SD = 2.2) (p < 0.001). Regarding physical activity, cases showed a significantly higher percentage of inactivity (62.1%) compared to controls (39.1%) (p = 0.046). Neuropathy exhibited a significant association with ulcer development, with 59.1% of cases having neuropathy compared to 23.5% of controls (p < 0.001). Furthermore, complications such as dry foot and fissures (60.0% vs. 6.3%), Charcot joint (36.8% vs. 12.2%), and foot trauma (40.9% vs. 3.9%) were significantly more prevalent in cases compared to controls (p < 0.001 for all). Conclusions The significant associations observed with advanced age, uncontrolled diabetes, longer diabetes duration, neuropathy, and specific foot complications underscore the multifactorial nature of ulcer development. The normal levels of vitamin B12 in most patients reflect no positive impact of normalized vitamin B12 levels on DFU. However, further observational studies with multiple vitamin B12 readings over a longer period are needed to establish its association with DFU development.

Vitamin B12 Deficiency in Thrombotic Thrombocytopenic Purpura-Like Cases.

Background: Thrombotic microangiopathies (TMA) are characterized by a triad of microangiopathic hemolytic anemia, thrombocytopenia, and organ damage which occur in the setting of endothelial damage and platelet activation. Vitamin B12 (cobalamin) deficiency could lead to a picture that resembles TMA, termed metabolic mediated TMA (MM-TMA). Case Presentation: A 60-year-old female was brought to the hospital after she was found unresponsive. On presentation, she was pale, lethargic, tachycardic, and febrile. Laboratory investigations revealed normocytic anemia, thrombocytopenia, and elevated bilirubin. Blood smear revealed schistocytes and tear drop cells. Given the presence of hemolytic anemia, thrombocytopenia, acute renal failure, and altered mental status, a presumptive diagnosis of thrombotic thrombocytopenic purpura (TTP) was made with a PLASMIC score of 7 indicating high risk. She received plasma exchange, caplacizumab, and intravenous methylprednisolone. Given the patient's low level of vitamin B12, she was initiated on intramuscular cyanocobalamin 1000 µg daily. The encephalopathy resolved and renal function improved. On day 6, ADAMTS13 activity was normal ruling out the diagnosis of TTP. Accordingly, plasmapheresis, steroids, and caplacizumab were discontinued. With continued aggressive B12 replacement, hemolysis resolved indicating severe vitamin B12 deficiency was the likely culprit of this patient's microangiopathic hemolytic anemia. Conclusion: This case serves to highlight the variable presentation of vitamin B12 deficiency. Severe vitamin B12 deficiency can even mimic TTP. If patients have markers of hemolysis, a low vitamin B12 level, and low reticulocyte count we should consider vitamin B12 deficiency as a likely cause of microangiopathic hemolytic anemia as early detection allows for early initiation of appropriate management. LEARNING POINTS: Vitamin B12 deficiency can be a cause of thrombotic microangiopathy.

A systematic review and meta-analysis of functional vitamin B12 status among adult vegans.

The dietary intake of vitamin B12 among unsupplemented vegans is notably lower compared to both vegetarians and omnivores. Prolonged low intakes of vitamin B12, such as seen in those adhering to a vegan diet, lead to physiological deficiency of vitamin B12 and an elevated risk of B12-related morbidity. However, while serum B12 serves as a conventional biomarker for assessing B12 status, its utility is limited given its sensitivity and specificity in ascribing physiological deficiency of B12 and the functional vitamin B12 status of those adhering to vegan diets is unclear. We conducted a systematic review and meta-analysis using data based on the full panel of biomarkers of vitamin B12 status to test whether adherence to a vegan diet is associated with an elevated risk of functional vitamin B12 deficiency compared to vegetarian or omnivorous diets. In addition, subgroup analysis was carried out to look at the effect of vitamin B12 supplement use on B12 status among vegans. Our search identified 4002 records, of which 19 studies met the inclusion criteria for the systematic review and 17 studies were taken forward for the meta-analysis. Meta-analysis results revealed significantly lower serum B12, pmol/ (-0.72 [-1.26, -0.18]; p = 0.01) and elevated total homocysteine, µmol/L (tHcy) (0.57 [0.26, 0.89]; p < 0.001) concentrations, alongside elevated methylmalonic acid, nmol/L (MMA) (0.28 [-0.01, 0.57]; p = 0.06) and lower holotranscobalamin, pmol/ (HoloTC) (-0.42 [-0.91, 0.07]; p = 0.09) levels among vegan adults compared to omnivores, indicating increased functional B12 deficiency in addition to low vitamin B12 status in vegan adults. There were no differences between vegans and vegetarians in HoloTC (0.04 [-0.28, 0.35]; p = 0.814) or MMA (-0.05 [-0.29, 0.20]; p = 0.708), but differences were found in serum B12 (-0.25 [-0.40, -0.10]; p = 0.001) and for tHcy (0.24 [0.09, 0.39]; p = 0.002) concentrations. Subgroup analyses indicated that the use of vitamin B12 supplements among vegans contributes to significant improvements in all biomarker concentrations compared to their unsupplemented counterparts. Our findings underscore the need for improved strategies to redress poor vitamin B12 status with appropriate B12 supplementation use among those adhering to vegetarian and vegan diets.

Genome-wide Association Study Identifies Genetic Polymorphisms for Folate-related Biomarkers in Chinese Preconception Women.

BACKGROUND: SNP allele frequencies, dietary habits, folate status and their associations vary across ethnic populations. Little is known about the SNPs accounting for variations of folate-related biomarkers for Chinese preparing-for-pregnant females. OBJECTIVE: We aimed to identify SNPs contributing to RBC and serum folate, vitamin B-12, and homocysteine levels in Chinese female preconception population. METHODS: A GWAS was conducted on 1000 randomly selected preconception Chinese women from SPCC. SNPs were genotyped using Illumina chips, and associations with biomarkers were assessed using simple linear regression models under the assumption of an additive genetic model. Genome-wide significance was considered at P < 10-7. RESULTS: The MTHFR rs1801133 was the major genetic coding variant contributing to RBC folate, serum folate and homocysteine concentrations (P=2.28×10-16; P=8.85×10-8, and P=2.46×10-13). It is associated with increased RBC folate (ß=0.154 per additional risk allele after log transform), decreased serum folate (ß=-0.951 per additional risk allele) and increased serum homocysteine concentrations (ß=1.153 per additional risk allele). The predominant SNP associated with serum folate was rs147162222 in NTRK2 (P=2.55×10-8) while the one associated with homocysteine was rs77025184 located between PDE7B and LINC00271 (P=4.91×10-17). For vitamin B-12, FUT2 rs1047781 was the dominant genetic variant (P=1.59×10-10). The numbers of signals with P value <10-7 for RBC folate, serum folate, vitamin B-12 and homocysteine were 12, 18, 8 and 614 respectively. CONCLUSIONS: This study represents the first GWAS focusing on folate-related biomarkers in a Chinese preparing-for-pregnant female population. The contributions of dominent SNPs to each biomarker were partly different from other populations. The study detected rs1801133 (C677T) in MTHFR as the predominant genetic variant contributing to RBC folate and rs1047781 (A385T) in FUT2 as the primary one explaining vitamin B-12. Notably, the intronic rs147162222 and non-coding rs77025184 were both first detected as the predominant SNPs for serum folate and homocysteine respectively.

Acute Mental Disorder Caused by Vitamin B12 Deficiency Eight Years After Total Gastrectomy.

Vitamin B12 deficiency can cause a variety of diseases. The most common disease is macrocytic anemia, but it has also been found to be a cause of psychiatric disorders. The causes of deficiency are varied, and diagnosis is often difficult. Here, we report a patient who developed mental disorders due to vitamin B12 deficiency after total gastrectomy. A 37-year-old female, eight years after total gastrectomy, was withdrawn at her workplace, talking and acting abnormally. The family had seen unusual behavior for three days. The patient had no particular history of mental illness. The possibility of herpes encephalitis was suspected, and the patient was referred to our hospital, but there were no specific findings in the head on imaging examination. Blood tests showed no macrocytic anemia. Spinal fluid cytology and electroencephalography showed no specific findings, and herpes DNA was negative. Metabolic factors such as vitamin deficiency were considered, and intravenous vitamin replacement therapy was initiated. The psychiatric symptoms improved rapidly after vitamin B12 supplementation was started. On the fifth day of her hospitalization, it was discovered that her vitamin B12 level at the time of admission was extremely low. Typically, vitamin B12 deficiency is associated with macrocytic anemia, but in this patient, serum iron was also decreased, indicating a mixed anemia, making the diagnosis difficult. The patient had undergone a total gastrectomy for gastric cancer eight years ago, and the psychiatric symptoms were thought to be due to impaired vitamin B12 absorption caused by intrinsic factor deficiency. Since then, oral replacement therapy and intramuscular injection have been continued without recurrence of symptoms. Disturbances of consciousness may have many causes, but when there is a history of gastrectomy, we should also consider vitamin B12 deficiency when examining patients.

Assessment of Vitamin D, Vitamin B12, and Folate Levels in Recently Identified Pregnant Females.

Background: Pregnancy is a critical period where optimal maternal and fetal health depends on adequate nutritional status. Deficiencies in essential vitamins, such as vitamin D, vitamin B12, and folate, can result in adverse health outcomes. Objective: This study aims to assess the serum levels of vitamin D, vitamin B12, and folate in early pregnancy. Methodology: This cross-sectional research was conducted at Kurdistan Private Hospital in Duhok, Kurdistan Region of Iraq, from September 2022 to October 2023. The study included 150 pregnant women, with ages ranging from 18 to 45 years. Serum levels of vitamin D, vitamin B12, and folate were measured using the Automatic Clinical Chemistry Analyzer COBAS e 411 (Roche Diagnostics, Basel, Switzerland). Results: The mean age of the participants was 29 years (standard deviation [SD] = 6.2 years), with ages ranging from 18 to 45 years. The average serum human chorionic gonadotropin (HCG) level was 4,292 mIU/mL (SD = 3,947 mIU/mL), with a range of 98 to 10,000 mIU/mL. The mean serum levels were 17.8 ng/mL (SD = 11.6) for vitamin D, 367 pg/mL (SD = 245) for vitamin B12, and 11.5 ng/mL (SD = 4.6) for folate. The prevalence of vitamin D deficiency was significant, with 92 participants (61.3%) having levels below 20 ng/mL, 39 participants (26%) having insufficient levels ranging from 20 to 29 ng/mL, and only 19 participants (12.7%) having sufficient levels between 30 and 100 ng/mL. No cases of vitamin D toxicity (>150 ng/mL) were observed. Regarding vitamin B12, 32 participants (21.3%) had deficient levels (<200 pg/mL), while 118 participants (78.7%) had normal levels. Folate analysis revealed that 3 participants (2%) had moderate deficiency (2-3 ng/mL), 14 participants (9.3%) had mild deficiency (3-6 ng/mL), and there were no cases of severe folate deficiency (<2 ng/mL). Pearson correlation analysis showed weak correlations between the study variables, with the strongest being a weak negative correlation between age and serum folate levels (-0.18). Conclusions: The study found a high prevalence of vitamin D deficiency among the pregnant women included in the study, while the levels of folate and vitamin B12 were comparable to worldwide estimates. These findings focus attention on the importance of monitoring and addressing nutritional deficiencies at the beginning and throughout pregnancy. They also underline the need for preventive health interventions to correct these deficiencies and achieve the best outcomes for both maternal and fetal health.

The influence of multivitamins on neurological and growth disorders: a cross-sectional study.

Background: While vitamin deficiencies can pose serious health consequences for the body, excessive intake of vitamins can also lead to health risks. However, there is limited data about the impact of multivitamins on neurological and growth disorders. This study aimed to investigate the relationship between multivitamins and neurological and growth disorders. Methods: A cross-sectional study was conducted with 16,921 subjects who visited the Children's Hospital of Nanjing Medical University from 2019 to 2021. The subjects were categorized into two groups based on their health status including 9,368 cases (4,484 with neurological disorders and 4,884 with growth disorders) and 7,553 healthy controls. Statistical tests including the T-test, Wilcoxon Rank Sum test, and Chi-Square test were employed to compare the groups, and logistic regression and Weighted Quantile Sum (WQS) regression were used to identify associations. Results: In the adjusted logistic regression, serum 25 hydroxyvitamin D [25(OH)D], vitamin B2, and vitamin B9 were associated with decreasing risks of neurological disorders, whereas vitamin A, vitamin B1, and vitamin B12 were associated with increasing risks of neurological disorders. Nevertheless, vitamin A and vitamin B2 were associated with increasing risks of growth disorders. In the WQS model, nine multivitamins were positively associated with risks of neurological disorders, and Vitamins D and C were weighted the most. In addition, the inverse association but not statistically significant was observed between multivitamins and growth disorders, particularly growth retardation revealed a negative association, and some individual growth disorders revealed positive associations including obesity and malnutrition. Conclusion: In general, the study observed that multivitamins may be associated with neurological and growth disorders either positive or negative depending on the type of disorder.

A Rare Case of Gastric Neuroendocrine Tumor in a Patient With Vitamin B12 Deficiency.

Vitamin B12 deficiency can result from gastric neuroendocrine tumors (GNETs), which are uncommon neoplasms frequently linked to hypergastrinemia and chronic atrophic gastritis. Here, we report the case of a 48-year-old vegetarian male from South India who presented with jaundice, fatigue, and gastrointestinal discomfort. He was diagnosed with macrocytic anemia, mild hepatomegaly, and significant vitamin B12 deficiency. An incidental upper gastrointestinal endoscopy revealed multiple gastric nodules, later confirmed as a well-differentiated GNET. The patient also had a high hepatitis B viral load. He was treated with vitamin B12 supplementation and underwent resection of the tumor followed by antiviral therapy for hepatitis B. Postoperative recovery was uneventful with improvements in anemia and liver function. This case emphasizes the importance of a multidisciplinary approach and thorough evaluation when addressing patients with vitamin B12 insufficiency, hepatitis B, and GNET.

Assessment of vitamin B12 and folate status and their determinants in children aged 6-59 months with severe acute malnutrition admitted to a tertiary-care centre in North India.

BACKGROUND: Vitamin B12 and folate are essential micronutrients, a deficiency of which causes anaemia, poor growth and an increased risk of infections, along with irreversible neurological damage to the developing brain in children. METHODS: A hospital-based prospective observational study was conducted in 100 children with severe acute malnutrition (SAM) aged 6-59 months admitted to a tertiary-care facility in northern India from July 2021 to June 2022. A structured proforma was used to record socio-demographic information, a detailed clinical history, results of general and systemic physical examination and a detailed anthropometric assessment. Serum folate and vitamin B12 were estimated by electrochemiluminescence. RESULTS: The mean age of the children was 24.18 months, and 64.0% were aged 6-12 months. The male-to-female ratio was 1.08:1. Anaemia was present in 87.0% of the children, and it was severe in 35% of them. There was serum vitamin B12 and folate deficiency in 61.0% and 19.0%, respectively. A deficiency of vitamin B12 was significantly associated with delayed developmental milestones in all domains, a mid-upper-arm circumference of <11.5 cm, severe anaemia, a low platelet count and folate deficiency, and a folate deficiency was significantly associated with older age, delayed developmental milestones in all domains, severe anaemia, a low platelet count and vitamin B12 deficiency. CONCLUSION: Vitamin B12 deficiency is highly prevalent in children aged 6-59 months with SAM, but the prevalence of folate deficiency is much lower. Apart from iron and folic acid supplementation, government programmes should consider vitamin B12 supplementation for children aged 6-59 months.

Effect of inulin on structural, physicochemical, and in vitro gastrointestinal tract release properties of core-shell hydrogel beads as a delivery system for vitamin B12.

In this study, core-shell hydrogel beads were developed as a controlled-release delivery system for vitamin B12. Vitamin B12-loaded microgels (MG) were prepared using gellan gum (GG). Core-shell hydrogel beads were produced by incorporating MG into pea protein isolate (PPI) and sodium alginate (AL) matrix filled/coated with different concentrations (0 %, 1 %, 3 %, 5 %, and 10 %) of inulin (IN). Based on XRD analysis, MG was successfully incorporated into core-shell hydrogel beads. In FE-SEM and FT-IR analyses, the smoother surface and denser structure of the beads were observed as IN concentration increased due to hydrogen bonds between IN and the beads. The encapsulation efficiency increased from 68.64 % to 82.36 % as IN concentration increased from 0 % to 10 %, respectively. After exposure to simulated oral and gastric conditions, core-shell hydrogel beads exhibited a lower cumulative release than MG, and a more sustained release was observed as IN concentration increased in simulated intestinal conditions.

Exploring the Impact of Folic Acid Supplementation and Vitamin B12 Deficiency on Maternal and Fetal Outcomes in Pregnant Women with Celiac Disease.

Background: Celiac disease is a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten, affecting approximately 1% of the global population and two million Americans. An increasing number of studies have identified a link between celiac disease and adverse maternal and fetal outcomes during pregnancy and after birth. Additionally, both celiac disease and pregnancy are associated with an increased risk for nutrient deficiencies, specifically vitamin B12 and folate. Methods: This review examines the current literature related to the folate trap and vitamin B12 deficiency in patients with celiac disease and pregnant women independently and provides rationale for future research to explore the relationship between the folate-to-12 ratio in pregnant women with celiac disease. Results: Deficiencies in vitamin B12 are linked with several negative maternal and fetal health outcomes including pre-eclampsia, gestational diabetes, spontaneous abortion/miscarriage, preterm birth, neural tube defects, intrauterine growth restriction, and low gestational age and birthweight. Conclusions: Folic acid supplementation is widely recommended during pregnancy, but complementary vitamin B12 supplementation is not standard. Physicians should consider celiac disease screening during pregnancy as well as vitamin B12 supplementation.

Aerobic adaptation and metabolic dynamics of Propionibacterium freudenreichii DSM 20271: insights from comparative transcriptomics and surfaceome analysis.

Propionibacterium freudenreichii (PFR) DSM 20271T is a bacterium known for its ability to thrive in diverse environments and to produce vitamin B12. Despite its anaerobic preference, recent studies have elucidated its ability to prosper in the presence of oxygen, prompting a deeper exploration of its physiology under aerobic conditions. Here, we investigated the response of DSM 20271T to aerobic growth by employing comparative transcriptomic and surfaceome analyses alongside metabolite profiling. Cultivation under controlled partial pressure of oxygen (pO2) conditions revealed significant increases in biomass formation and altered metabolite production, notably of vitamin B12, pseudovitamin-B12, propionate, and acetate, under aerobic conditions. Transcriptomic analysis identified differential expression of genes involved in lactate metabolism, tricarboxylic acid cycle, and electron transport chain, suggesting metabolic adjustments to aerobic environments. Moreover, surfaceome analysis unveiled growth environment-dependent changes in surface protein abundance, with implications for adaptation to atmospheric conditions. Supplementation experiments with key compounds highlighted the potential for enhancing aerobic growth, emphasizing the importance of iron and α-ketoglutarate availability. Furthermore, in liquid culture, FeSO4 supplementation led to increased heme production and reduced vitamin B12 production, highlighting the impact of oxygen and iron availability on the metabolic pathways. These findings deepen our understanding of PFR's physiological responses to oxygen availability and offer insights for optimizing its growth in industrial applications. IMPORTANCE: The study of the response of Propionibacterium freudenreichii to aerobic growth is crucial for understanding how this bacterium adapts to different environments and produces essential compounds like vitamin B12. By investigating its physiological changes under aerobic conditions, we can gain insights into its metabolic adjustments and potential for enhanced growth. These findings not only deepen our understanding of P. freudenreichii's responses to oxygen availability but also offer valuable information for optimizing its growth in industrial applications. This research sheds light on the adaptive mechanisms of this bacterium, providing a foundation for further exploration and potential applications in various fields.