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Abstract Background Imerslund-Gräsbeck syndrome (IGS) is a rare autosomal recessive disorder characterized by megaloblastic anemia due to selective cobalamin malabsorption and benign proteinuria. IGS is caused by a disfunction of the cubam receptor, which mediates the reabsorption of cobalamin in the ileum and the reuptake of albumin in renal proximal tubules. Case presentation We describe the case of a 23-month-old-italian infant presenting with severe pancytopenia and failure to thrive in whom the diagnosis of IGS was made and vitamin B12 replacement therapy was resolutive. Genetic analysis (NGS with CNV analysis including 214 genes involved in bone marrow failure and anemia), showed the presence of two pathogenetic variants in the AMN gene (c-208–2 A > G and c.1006 + 34_1007-31del). These variants have been previously described in the literature, but their combination has never been reported. Conclusions Imerslund-Gräsbeck syndrome should be considered in the differential diagnosis of children with severe pancytopenia even in those without neurological involvement. This case emphasizes the importance of an early diagnosis and prompt treatment, to prevent irreversible neurological injury.

Vitamin B12 deficiency is a common condition that causes a variety of disorders ranging from the development of megaloblastic anemia to the building up of neurological damage. Historically one of the leading causes of B12 deficiency appears to be secondary to malabsorption in part caused by the development of atrophic gastritis in pernicious anemia. More recently B12 deficiency could also depend on dietary restrictions. Cobalamin deficiency also appears to be closely related to folate metabolism, causing a reduction in methionine synthase activity. This results in the accumulation of 5-methyltetrahydrofolate (5-MTHF) and defective DNA synthesis. It has been hypothesized that reduced activity of the enzyme methylene-tetrahydrofolate reductase (MTHFR) could reduce the production of 5-MTHF, thereby shifting folate metabolism to thymidylate synthesis and promoting proper DNA synthesis. Our aim was to investigate the role of the C677T and A1298C MTHFR gene polymorphisms, which are associated with reduced enzyme activity, in predisposing to the development of anemia, neurological symptoms, and atrophic gastritis in a population of 105 consecutive Italian patients with cobalamin deficiency. We found statistically significant correlations between the degree of anemia and thrombocytopenia and the C677T MTHFR polymorphism, while hemoglobin levels alone significantly correlated with A1298C polymorphism, contradicting the potential protective role of these polymorphisms. Furthermore, in patients with atrophic gastritis, we found an association between the absence of parietal cell antibodies and the presence of the C677T polymorphism in homozygosity. Our results suggest a role for MTHFR enzyme activity in the severity of hematologic manifestations of vitamin B12 deficiency and as an independent mechanism of predisposition to the development of atrophic gastritis. [ABSTRACT FROM AUTHOR]

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.

OBJECTIVE: To evaluate the fecal bacterial microbiota at the time of diagnosis (T0) and after 1 month of therapy (T1) in cats diagnosed with lymphoplasmacytic enteritis (LPE) or cats with low-grade intestinal T-cell lymphoma (LGITL) and to compare these findings with those of healthy cats. ANIMALS: 5 healthy cats, 13 cats with LPE, and 7 cats with LGITL were prospectively enrolled between June 2020 and June 2021. METHODS: Fecal samples were collected at T0 and T1, and DNA was extracted for 16S ribosomal amplicon sequencing. Alpha diversity and beta diversity were computed. The taxonomic assignment was performed using sequences from the Silva v138 formatted reference database. Differential abundant taxa were selected in each taxonomic level, with the P value adjusted < .05, as the cut-off. RESULTS: No significant differences in alpha and beta diversity were found either at T0 or T1 between healthy and diseased cats or between cats with LPE and LGITL. Beta-diversity analysis showed an increase in the Fusobacteriaceae family in cats with LGITL at T0, compared to cats with LPE. Regardless of histological diagnosis, several microbiota differences were found at T0 based on serum cobalamin levels. CLINICAL RELEVANCE: Fecal samples were successfully used to characterize the bacteriome of the intestinal tract in cats by 16S rRNA gene sequencing. However, results highlighted that the metagenomic evaluation was not useful to discriminate between LPE and LGITL nor to predict the therapeutic response in this study population. [ABSTRACT FROM AUTHOR]

Transcobalamin II (TC) promotes the cellular uptake of cobalamin (Cbl) through receptor-mediated endocytosis of the TC-cbl complex in peripheral tissues. TC deficiency is a rare disorder that causes intracellular Cbl depletion. It presents in early infancy with a failure to thrive, diarrhea, anemia, agammaglobulinemia, and pancytopenia. Data from five TC-deficient patients including clinical, biochemical, and molecular findings, as well as long-term outcomes, were collected. Mutation analysis revealed one unreported pathogenic variant in the TCN2 gene. One patient had exocrine pancreatic insufficiency. We conducted a retrospective analysis of C3 and C3/C2 from dried blood samples, as this is implemented for newborn screening (NBS). We detected a marked increase in the C3/C2 ratio in two samples. Treatment was based on parenteral Cbl. Three patients treated before six months of age had an initial favorable outcome, whereas the two treated later or inadequately had neurological impairment. This is the first report of Argentinean patients with TC deficiency that detected a new variant in TCN2. NBS may be a tool for the early detection of TC deficiency. This data emphasizes that TC deficiency is a severe disorder that requires early detection and long-term, aggressive therapy. Accurate diagnosis is imperative, because early detection and treatment can be life-saving. [ABSTRACT FROM AUTHOR]

Introduction: Vitamin B12 is a water-soluble vitamin found primarily in animal-derived products such as red meat, dairy, and eggs. An essential substance for its absorption is the intrinsic factor, produced by the parietal cells of the stomach. After absorption in the distal ileum, cobalamin acts as a coenzyme in DNA synthesis and the metabolism of fatty acids and homocysteine. In addition to its well-known influence on the nervous system, it has been associated with gastrointestinal diseases according to numerous authors. Objective: The objective of this study is to gather and analyze literature regarding the associations between vitamin B12 deficiency and gastrointestinal diseases, including gastroesophageal reflux disease (GERD), gastritis, inflammatory bowel disease (IBD), small intestinal bacterial overgrowth (SIBO), and hepatitis C (HCV). Materials and Methods: A literature review was conducted using the PubMed database with the following search terms: vitamin B12, cobalamin, deficiency, gastrointestinal diseases, GERD, IBD, SIBO, HCV. Current Knowledge: Vitamin B12 deficiency can be caused by autoimmune factors, dietary insufficiencies, toxin exposure, and malabsorption disorders related to gastrointestinal diseases. Gastrointestinal conditions such as GERD and IBD can both lead to and be exacerbated by cobalamin deficiency. Furthermore, vitamin B12 deficiency may be worsened by prolonged use of proton pump inhibitors (PPIs) and Helicobacter pylori infection. Conclusions: An adequate amount of vitamin B12 is crucial for gastrointestinal health. Deficiency can significantly impact the course and symptoms of many gastrointestinal diseases. Therefore, monitoring and supplementation of vitamin B12 should be an integral part of managing patients with gastrointestinal conditions.

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

There is a clinical need for early detection of chronic kidney disease (CKD) in patients with organic acidurias. We measured kidney markers in a longitudinal study over 5 years in 40 patients with methylmalonic aciduria (Mut0), propionic aciduria (PA), cobalamin A (CblA), and cobalamin C (CblC) deficiencies. Neutrophil gelatinase‐associated lipocalin (NGAL), calprotectin (CLP), kidney injury molecule‐1 (KIM‐1), dickkopf‐3 (DKK‐3), albumin and beta‐2‐microglobulin (B2MG) in urine, as well as cystatin C (CysC) in serum were quantified. In Mut0 patients, mean concentrations of B2MG, KIM‐1, and DKK‐3 were elevated compared with healthy controls, all markers indicative of proximal tubule damage. In PA patients, mean B2MG, albumin, and CLP were elevated, indicating signs of proximal tubule and glomerulus damage and inflammation. In CblC patients, mean B2MG, NGAL, and CLP were increased, and considered as markers for proximal and distal tubule damage and inflammation. B2MG, was elevated in all three diseases, and correlated with DKK‐3 in Mut0/CblA and with eGFR(CysC) and KIM‐1 in PA patients, respectively. None of the markers were elevated in CblA patients. Significant deterioration of kidney function, as determined by steady increase in CysC concentrations was noted in seven patients within the observation period. None of the investigated biomarker profiles showed a clear increase or added value for early detection. In conclusion, we identified disease‐specific biomarker profiles for inflammation, tubular, and proximal damage in the urine of Mut0, PA, and CblC patients. Whether these biomarkers can be used for early detection of CKD requires further investigation, as significant kidney function deterioration was observed in only a few patients. [ABSTRACT FROM AUTHOR]

Abstract Background Low serum cobalamin concentrations have been associated with ileal malabsorption in dogs with chronic enteropathy. Increased serum methylmalonic acid (MMA) concentrations indicate cobalamin deficiency on a cellular level. Few studies have evaluated serum cobalamin concentrations or methylmalonic acid concentrations in juvenile dogs with parvoviral enteritis or nonparvoviral acute enteropathies. Objectives Evaluate serum cobalamin and methylmalonic acid concentrations in juvenile dogs (6 weeks to 10 months old) with parvoviral enteritis or nonparvoviral acute enteropathy. Animals Thirty‐one juvenile dogs with parvoviral enteritis, 29 dogs with nonparvoviral acute diarrhea (NPVAD), and 40 healthy juvenile control dogs. Methods Single‐center, prospective, observational, cross‐sectional study. Serum cobalamin and, when sufficient serum was available, MMA concentrations were measured. Results Most serum cobalamin concentrations were within the adult reference interval. Serum cobalamin concentrations in healthy dogs (median, 848 ng/L; range, 293‐1912 ng/L) were significantly higher than in dogs with parvoviral enteritis (P = .0002; median, 463 ng/L; range,

Vitamin B12 is an essential water-soluble vitamin, which is vital in the production of red blood cells, nervous system function, and DNA synthesis during cell division. Vitamin B12 deficiency is a condition resulted from inadequate intake or malabsorption of vitamin B12. Severe B12 deficiency could lead to pernicious anaemia, mental impairment, and neurological disorders. Therefore, careful management and treatment are pivotal. This deficiency is commonly treated with B12 injections in Primary Care. However, review of literature showed that oral B12 supplementation was as effective as parenteral treatment. To minimise ambiguity in administering B12 injections, several clinical guidelines were highlighted. Nevertheless, further research is needed to evaluate the effectiveness of oral B12 therapy. [ABSTRACT FROM AUTHOR]

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

Newborn screening (NBS) programs are effective measures of secondary prevention and have been successively extended. We aimed to evaluate NBS for methylmalonic acidurias, propionic acidemia, homocystinuria, remethylation disorders and neonatal vitamin B12 deficiency, and report on the identification of cofactor-responsive disease variants. This evaluation of the previously established combined multiple-tier NBS algorithm is part of the prospective pilot study "NGS2025" from August 2016 to September 2022. In 548,707 newborns, the combined algorithm was applied and led to positive NBS results in 458 of them. Overall, 166 newborns (prevalence 1: 3305) were confirmed (positive predictive value: 0.36); specifically, methylmalonic acidurias (N = 5), propionic acidemia (N = 4), remethylation disorders (N = 4), cystathionine beta-synthase (CBS) deficiency (N = 1) and neonatal vitamin B12 deficiency (N = 153). The majority of the identified newborns were asymptomatic at the time of the first NBS report (total: 161/166, inherited metabolic diseases: 9/14, vitamin B12 deficiency: 153/153). Three individuals were cofactor-responsive (methylmalonic acidurias: 2, CBS deficiency: 1), and could be treated by vitamin B12, vitamin B6 respectively, only. In conclusion, the combined NBS algorithm is technically feasible, allows the identification of attenuated and severe disease courses and can be considered to be evaluated for inclusion in national NBS panels. [ABSTRACT FROM AUTHOR]

Abstract Background There is a paucity of studies reporting the presence of systemic symptoms and micronutrient deficiency in patients with chronic urticaria, and these data are lacking in a Canadian population. Objective To report the prevalence of gastrointestinal symptoms and vitamin B12 (cobalamin) deficiency in a Canadian patient population diagnosed with chronic urticaria. Methods A retrospective chart review of 100 adult patients with chronic urticaria was conducted. Demographic characteristics, medications, presence of gastrointestinal symptoms, and laboratory findings were abstracted from electronic medical records. Results Seventy percent of patients with chronic urticaria reported experiencing gastrointestinal symptoms. The most common symptom identified was gastroesophageal reflux (42%). Vitamin B12 (cobalamin) deficiency, defined as serum vitamin B12 level ≤ 250 pmol/L, was identified in 31.7% of the patients. Among those patients with urticaria and vitamin B12, 68% reported gastrointestinal symptoms. Conclusions This is the first study to provide data on the high prevalence of gastrointestinal symptoms and vitamin B12 (cobalamin) deficiency in a Canadian population diagnosed with chronic urticaria. Early recognition and management of systemic symptoms and micronutrient deficiency may lead to a more comprehensive approach to management of these patients. Trial registration Not applicable

Purpose Primary aldosteronism is one of the most frequent causes of secondary arterial hypertension, and whether primary aldosteronism is associated with masked hypertension is unknown. Materials and methods We describe a 64-year-old man with a history of hypothyroidism, recurring hypokalaemia, and normal home and office blood pressure values. Ambulatory blood pressure monitoring revealed masked hypertension with strikingly high systolic blood pressure variability and typical hypertension-mediated organ damage. Results The patient required gradual escalation of antihypertensive medication to four drugs. During the diagnostic process we identified primary aldosteronism, cobalamin deficiency, severe obstructive sleep apnoea, and low baroreflex sensitivity (1.63 ms/mmHg). Following unilateral adrenalectomy, cobalamin supplementation and continuous positive airway pressure, we observed a spectacular improvement in the patient’s blood pressure control, baroreflex sensitivity (4.82 ms/mmHg) and quality of life. Conclusions We report an unusual case of both masked arterial hypertension and primary aldosteronism. Elevated blood pressure values were masked in home and office measurements by coexisting hypotension which resulted most probably from deteriorated baroreflex sensitivity. Baroreflex sensitivity increased following treatment, including unilateral adrenalectomy. Hypertension can be masked by coexisting baroreceptor dysfunction which may derive from structural but also functional reversible changes.

Background: Low serum cobalamin concentrations have been associated with ileal malabsorption in dogs with chronic enteropathy. Increased serum methylmalonic acid (MMA) concentrations indicate cobalamin deficiency on a cellular level. Few studies have evaluated serum cobalamin concentrations or methylmalonic acid concentrations in juvenile dogs with parvoviral enteritis or nonparvoviral acute enteropathies. Objectives: Evaluate serum cobalamin and methylmalonic acid concentrations in juvenile dogs (6 weeks to 10 months old) with parvoviral enteritis or nonparvoviral acute enteropathy. Animals: Thirty‐one juvenile dogs with parvoviral enteritis, 29 dogs with nonparvoviral acute diarrhea (NPVAD), and 40 healthy juvenile control dogs. Methods: Single‐center, prospective, observational, cross‐sectional study. Serum cobalamin and, when sufficient serum was available, MMA concentrations were measured. Results: Most serum cobalamin concentrations were within the adult reference interval. Serum cobalamin concentrations in healthy dogs (median, 848 ng/L; range, 293‐1912 ng/L) were significantly higher than in dogs with parvoviral enteritis (P =.0002; median, 463 ng/L; range, <150‐10 000 ng/L) or dogs with NPVAD (P =.02; median, 528 ng/L; range, 160‐8998 ng/L). Serum MMA concentrations were not significantly different between groups (healthy dogs: median, 796 nmol/L; range, 427‐1933 nmol/L; parvoviral enteritis: median, 858 nmol/L; range, 554‐3424 nmol/L; NPVAD: median, 764 nmol/L; range, 392‐1222 nmol/L; P =.1). Conclusions and Clinical Importance: Juvenile dogs with parvoviral enteritis or NPVAD had lower serum cobalamin concentrations than healthy juvenile dogs. However, based on serum MMA concentrations cellular cobalamin deficiency was not apparent. [ABSTRACT FROM AUTHOR]

Abstract Background Recent studies have shown similar efficacy of oral supplementation of cobalamin compared to injectable supplementation in dogs, but few prospective, randomized studies have been published. Objectives To evaluate efficacy of oral or injectable supplementation with cobalamin in normalizing serum cobalamin and methylmalonic acid (MMA) concentrations in dogs with hypocobalaminemia caused by either chronic enteropathy (CE) or exocrine pancreatic insufficiency (EPI). Animals Forty‐six client owned dogs with hypocobalaminemia. Methods Prospective randomized clinical trial. Dogs were divided into 2 groups (CE or EPI), and randomized to receive oral or injectable supplementation of cobalamin. Each dog had 3 visits and serum cobalamin and MMA concentrations were measured at each visit. Results In dogs with CE, serum cobalamin concentrations increased with oral (P = .02; median 149 [range 149‐231] to 733 [166‐1467] ng/L, median difference 552 [95% CI: 181‐899] ng/L) or injectable (P

Background: There is a paucity of studies reporting the presence of systemic symptoms and micronutrient deficiency in patients with chronic urticaria, and these data are lacking in a Canadian population. Objective: To report the prevalence of gastrointestinal symptoms and vitamin B12 (cobalamin) deficiency in a Canadian patient population diagnosed with chronic urticaria. Methods: A retrospective chart review of 100 adult patients with chronic urticaria was conducted. Demographic characteristics, medications, presence of gastrointestinal symptoms, and laboratory findings were abstracted from electronic medical records. Results: Seventy percent of patients with chronic urticaria reported experiencing gastrointestinal symptoms. The most common symptom identified was gastroesophageal reflux (42%). Vitamin B12 (cobalamin) deficiency, defined as serum vitamin B12 level ≤ 250 pmol/L, was identified in 31.7% of the patients. Among those patients with urticaria and vitamin B12, 68% reported gastrointestinal symptoms. Conclusions: This is the first study to provide data on the high prevalence of gastrointestinal symptoms and vitamin B12 (cobalamin) deficiency in a Canadian population diagnosed with chronic urticaria. Early recognition and management of systemic symptoms and micronutrient deficiency may lead to a more comprehensive approach to management of these patients. Trial registration Not applicable [ABSTRACT FROM AUTHOR]

Disorders of vitamin B12 (cobalamin) metabolism in children can be manifested by numerous symptoms. They result from the dysfunction of many systems, including the central nervous system. The most common cause of cobalamin deficiency in infants is inadequate supplementation of the vitamin with food. This mainly affects children who are exclusively breastfed by mothers who follow a diet with insufficient supplementation of vitamin B12, including an imbalanced vegetarian or vegan diet. Adequate vitamin B12 supplementation is essential for the proper growth and development of a child. However, attempts to compensate for severe vitamin B12 deficiency can paradoxically B12 deficiency with megaloblastic anemia. The boy developed pathological neurological signs after intramuscular injections of vitamin B12. The symptoms included muscle tremors of the upper extremities, head, tongue, and lips. A broad differential diagnosis including inborn errors of metabolism and other genetic disorders is discussed. We describe treatment that led to the complete resolution of symptoms related to the side effects of the B12 therapy. The patient's psychomotor development during over 1 year of clinical follow-up is also analyzed. [ABSTRACT FROM AUTHOR]

Primary aldosteronism is one of the most frequent causes of secondary arterial hypertension, and whether primary aldosteronism is associated with masked hypertension is unknown. We describe a 64-year-old man with a history of hypothyroidism, recurring hypokalaemia, and normal home and office blood pressure values. Ambulatory blood pressure monitoring revealed masked hypertension with strikingly high systolic blood pressure variability and typical hypertension-mediated organ damage. The patient required gradual escalation of antihypertensive medication to four drugs. During the diagnostic process we identified primary aldosteronism, cobalamin deficiency, severe obstructive sleep apnoea, and low baroreflex sensitivity (1.63 ms/mmHg). Following unilateral adrenalectomy, cobalamin supplementation and continuous positive airway pressure, we observed a spectacular improvement in the patient's blood pressure control, baroreflex sensitivity (4.82 ms/mmHg) and quality of life. We report an unusual case of both masked arterial hypertension and primary aldosteronism. Elevated blood pressure values were masked in home and office measurements by coexisting hypotension which resulted most probably from deteriorated baroreflex sensitivity. Baroreflex sensitivity increased following treatment, including unilateral adrenalectomy. Hypertension can be masked by coexisting baroreceptor dysfunction which may derive from structural but also functional reversible changes. [ABSTRACT FROM AUTHOR]

Cobalamin (vitamin B12) deficiency is one of the major factors causing degenerative changes in the nervous system and, thus, various neurological and psychiatric symptoms. The underlying cellular mechanism of this phenomenon is not yet fully understood. An accumulation of senescent astrocytes has been shown to contribute to a wide range of pathologies of the nervous system, including neurodegenerative disorders. This study aimed to investigate whether cobalamin deficiency triggers astrosenescence. After inducing cobalamin deficiency in normal human astrocytes in vitro, we examined biomarkers of cellular senescence: SA-β-gal, p16INK4A, and p21Waf1/Cip1 and performed cell nuclei measurements. The obtained results may contribute to an increase in the knowledge of the cellular effects of cobalamin deficiency in the context of astrocytes. In addition, the presented data suggest a potential causative agent of astrosenescence that has not been proven to date. [ABSTRACT FROM AUTHOR]

Acquired vitamin B12 (vB12) deficiency (vB12D) of newborns is relatively frequent as compared with the incidence of inherited diseases included in newborn screening (NBS) of different countries across the globe. Infants may present signs of vB12D before 6 months of age with anemia and/or neurologic symptoms when not diagnosed in asymptomatic state. The possibility of identifying vitamin deficient mothers after their pregnancy during the breastfeeding period could be an additional benefit of the newborn screening. Vitamin supplementation is widely available and easy to administer. However, in many laboratories, vB12D is not included in the national screening program. Optimized screening requires either second-tier testing or analysis of new urine and blood samples combined with multiple clinical and laboratory follow ups. Our scope was to review the physiologic fate of vB12 and the pathobiochemical consequences of vB12D in the human body. Particular emphasis was put on the latest approaches for diagnosis and treatment of vB12D in NBS. [ABSTRACT FROM AUTHOR]

Background: Hypoadrenocorticism in cats is uncommonly reported. Most reports consist of cats with hyponatremia, hyperkalemia, or both., Hypothesis/objectives: To describe clinical findings, treatment response, and outcome in cats diagnosed with hypoadrenocorticism, including cats with abnormal and normal serum sodium and potassium concentrations., Animals: Forty-one cats with hypoadrenocorticism; 36 with and 5 without abnormal serum sodium and potassium concentrations., Methods: Multicenter retrospective observational study. Data for the entire cohort were assessed using descriptive statistics and differences between cats with and without abnormal serum sodium and potassium concentrations were evaluated., Results: Median age was 5.7 years (range, 0.2-13.8). Twenty-three (56%) cats were male and 18 (44%) were female. Cats with hyponatremia, hyperkalemia, or both were less likely to have a history of vomiting (P = .01) but more likely to be hypothermic (P = .03), dehydrated (P = .04) or weak (P = .04) on examination, compared with nonhyponatremic and nonhyperkalemic cats. Frequency of hypercalcemia was 31.7%. Exocrine pancreatic insufficiency (EPI) was diagnosed in 4/7 cats tested; all 4 had concurrent cobalamin deficiency. Thirty-five (85.4%) cats survived to discharge. In 2 cats, hypoadrenocorticism occurred secondary to lymphoma. Median survival time (MST) for all-cause mortality was 2035 days (95% confidence interval [CI], 294-4380 days); MST for disease-specific mortality was not reached., Conclusions and Clinical Importance: Approximately one-third of cats with hypoadrenocorticism had hypercalcemia. In some cases, hyponatremia and hyperkalemia were not observed. Cats with nonneoplastic associated hypoadrenocorticism that survive initial hospitalization can have a favorable long-term prognosis. Testing for EPI may be warranted in cats with hypoadrenocorticism., (© 2024 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Vitamin B12 deficiency can present with hematological and neuropsychiatric manifestations and is most commonly due to pernicious anemia in adults. A rare presentation is pseudo-thrombotic microangiopathy, which mimics thrombotic microangiopathies and may result in unwarranted treatment, including plasmapheresis. This condition must be considered in patients presenting with features of microangiopathic hemolytic anemia, and prompt treatment with vitamin B12 supplementation should be initiated. Although the laboratory findings of pseudo-thrombotic microangiopathy are similar to those of thrombotic thrombocytopenic purpura, there are some significant differences, such as in the reticulocyte production index. This report presents the case of a patient with pseudo-thrombotic microangiopathy caused by vitamin B12​​​​​​​ deficiency., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: Ana Azevedo declare(s) personal fees from Alexion, AstraZeneca, Sanofi and Lilly . Ana Azevedo has received fees from Alexion, AstraZeneca, Sanofi and Lilly for participating in expert meetings and teaching courses. Andreia Ribeiro declare(s) personal fees from ViiV Healthcare. Andreia Ribeiro has received fees from ViiV Healthcare for participating in expert meetings and teaching courses. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Tavares Pereira et al.)

Context: Cobalamin and folate are essential for the synthesis of nucleic acids and in the maintenance of myelin. They are required during the period of the rapid growth of infancy and childhood. Their deficiency may result in nutritional anemia and neurological manifestations. There is paucity of literature regarding the prevalence of cobalamin and folate deficiency among North Indian children aged 6–59 months. Aim: The aim of this study was to estimate the prevalence of serum cobalamin and folate deficiency among children aged 6–59 months, attending a secondary care hospital. Settings and Design: Children were recruited from pediatrics OPD of the sub-district hospital (SDH), Ballabgarh, Haryana, through systematic random sampling. Hemoglobin was measured by an automated analyzer. Serum cobalamin and serum folate were estimated using enhanced chemiluminescence based immunoassay. Results: A total of 420 children were recruited, of which 392 provided a blood specimen. Prevalence of cobalamin, folate deficiency, and anemia were 22.3% (95% CI: 18.3–26.7), 10.9% (95% CI: 8.2–14.6), and 81.9% (95% CI 77.7–85.4), respectively. The proportion of children with cobalamin deficiency who had anemia was 97.7% compared to 95.7% among those with no cobalamin deficiency (P = 0.396). Similarly, the proportion of children with folate deficiency who had anemia was 95.2% compared to 96.2% among those with no folate deficiency (P = 0.765). Conclusion: We found that almost one in five children aged 6–59 were deficient in cobalamin, and one in ten were deficient in folate.

Background: Recent studies have shown similar efficacy of oral supplementation of cobalamin compared to injectable supplementation in dogs, but few prospective, randomized studies have been published. Objectives: To evaluate efficacy of oral or injectable supplementation with cobalamin in normalizing serum cobalamin and methylmalonic acid (MMA) concentrations in dogs with hypocobalaminemia caused by either chronic enteropathy (CE) or exocrine pancreatic insufficiency (EPI). Animals: Forty‐six client owned dogs with hypocobalaminemia. Methods: Prospective randomized clinical trial. Dogs were divided into 2 groups (CE or EPI), and randomized to receive oral or injectable supplementation of cobalamin. Each dog had 3 visits and serum cobalamin and MMA concentrations were measured at each visit. Results: In dogs with CE, serum cobalamin concentrations increased with oral (P =.02; median 149 [range 149‐231] to 733 [166‐1467] ng/L, median difference 552 [95% CI: 181‐899] ng/L) or injectable (P <.01; 168 [149‐233] to 563 [234‐965] ng/L, 367 [187‐623] ng/L) supplementation. In dogs with EPI, serum cobalamin concentrations increased with oral (P =.01; 162 [149‐214] to 919 [643‐3863] ng/L, 705 [503‐3356] ng/L) or injectable (P =.01; 177 [149‐217] to 390 [243‐907] ng/L, 192 [89‐361] ng/L) supplementation. Serum MMA concentrations decreased with oral or injectable supplementation in dogs with CE, but only with oral supplementation in dogs with EPI. Conclusions and Clinical Importance: Oral supplementation is an alternative for cobalamin supplementation in dogs with hypocobalaminemia caused by CE or EPI. [ABSTRACT FROM AUTHOR]

Objective: Primary headaches are common and benign discomforts both in children and adolescents. However, they have a negative influence on the quality of life. This retrospective study aimed to determine the relationship between vitamin B12 results and primary headaches in Turkish children. Methods: Demographical features, headache types, laboratory results, including vitamin B12, were assessed retrospectively. Headache types were categorized as tension-type headache, migraine, and unclassified headache according to the International Classification of Headache Disorders-beta version (ICD-3 beta). Patients with seconder headaches, anemia, and macrocytosis were excluded. Results: The study group consisted of 133 (86 female, 47 male) patients with headache and a control group of 103 (57 female, 46 male) healthy children. There was no significant difference in terms of age and gender between groups (p>0.05). Vitamin B₁₂ levels in tension-type headache, migraine, and unclassified headache groups were significantly lower (p

Abstract Background Pyoderma gangrenosum (PG) is an uncommon, idiopathic, ulcerative neutrophilic dermatosis. In many cases, PG is associated with a wide variety of different disorders but SLE in association with PG is relatively uncommon. In this article we present the case of a middle aged patient with PG as the initial clinical presentation of SLE. We also provide a brief review of cobalamin deficiency which occurred in our patient and evidence-based management options. Case presentation A 35 years old man presented with a 5 month history of debilitating painful lower limb and scrotal ulcers. This was associated with polyarthralgia and morning stiffness involving both hands. He also complained of swallowing difficulties. He had unintentional weight loss of 10 kg and fatigue. Physical examination revealed alopecia, multiple cervical lymphadenopathies, bilateral parotid gland enlargement and atrophic glossitis. There was Raynaud’s phenomenon noted over both hands and generalised hyper-pigmented fragile skin. Laboratory results disclosed anaemia, leukopenia, hyponatraemia and hypocortisolism. Detailed anaemic workup revealed low serum ferritin and cobalamin level. The autoimmune screen showed positive ANA, anti SmD1, anti SS-A/Ro 52, anti SSA/Ro 60, anti U1-snRNP with low complement levels. Upper gastrointestinal endoscopy with biopsies confirmed atrophic gastritis and duodenitis. Intrinsic factor antibodies and anti-tissue transglutaminase IgA were all negative. Punch biopsies of the leg ulcer showed neutrophilic dermatosis consistent with pyoderma gangrenosum. Based on the clinical findings and positive immunologic studies, he was diagnosed as systemic lupus erythematosus. His general condition improved substantially with commencement of corticosteroids, immunosuppressants and vitamin supplements. Conclusions We report a case of PG as the first manifestation of SLE which was treated successfully with immunosuppressants and vitamin supplements. Our report highlighted the need to consider connective tissue diseases such as SLE in a patient presenting with PG in order for appropriate treatment to be instituted thereby achieving a good outcome.

Context: Cobalamin and folate are essential for the synthesis of nucleic acids and in the maintenance of myelin. They are required during the period of the rapid growth of infancy and childhood. Their deficiency may result in nutritional anemia and neurological manifestations. There is paucity of literature regarding the prevalence of cobalamin and folate deficiency among North Indian children aged 6–59 months. Aim: The aim of this study was to estimate the prevalence of serum cobalamin and folate deficiency among children aged 6–59 months, attending a secondary care hospital. Settings and Design: Children were recruited from pediatrics OPD of the sub-district hospital (SDH), Ballabgarh, Haryana, through systematic random sampling. Hemoglobin was measured by an automated analyzer. Serum cobalamin and serum folate were estimated using enhanced chemiluminescence based immunoassay. Results: A total of 420 children were recruited, of which 392 provided a blood specimen. Prevalence of cobalamin, folate deficiency, and anemia were 22.3% (95% CI: 18.3–26.7), 10.9% (95% CI: 8.2–14.6), and 81.9% (95% CI 77.7–85.4), respectively. The proportion of children with cobalamin deficiency who had anemia was 97.7% compared to 95.7% among those with no cobalamin deficiency (P = 0.396). Similarly, the proportion of children with folate deficiency who had anemia was 95.2% compared to 96.2% among those with no folate deficiency (P = 0.765). Conclusion: We found that almost one in five children aged 6–59 were deficient in cobalamin, and one in ten were deficient in folate. [ABSTRACT FROM AUTHOR]

Autoimmune polyglandular syndromes (APS) are rare disorders characterized by auto‐destruction of endocrine and non‐endocrine organs by organ‐specific antibody‐directed T‐lymphocytic infiltration. This case highlights a 29‐year‐old Caucasian man with vitiligo found to have significant neurological abnormalities in the setting of newly diagnosed pernicious anemia and thyroid autoimmune disease. [ABSTRACT FROM AUTHOR]

Abstract Background Hereditary intrinsic factor deficiency is a rare disease characterized by cobalamin deficiency with the lack of gastric intrinsic factor because of gastric intrinsic factor (GIF) mutations. Patients usually present with cobalamin deficiency without gastroscopy abnormality and intrinsic factor antibodies. Case presentation A Chinese patient presented with recurrent severe anemia since age 2 with low cobalamin level and a mild elevation of indirect bilirubin. The hemoglobin level normalized each time after intramuscular vitamin B12 injection. Gene test verified a c.776delA frame shift mutation in exon 6 combined with c.585C > A nonsense early termination mutation in exon 5 of GIF which result in the dysfunction of gastric intrinsic factor protein. The hereditary intrinsic factor deficiency in literature was further reviewed and the ancestry of different mutation sites were discussed. Conclusions A novel compound heterozygous mutation of GIF in a Chinese patient of hereditary intrinsic factor deficiency was reported. It was the first identified mutation of GIF in East-Asia and may indicate a new ancestry.

Introduction: Clinical manifestations of vitamin B12 deficiency are mostly non-specific. An entity called subclinical deficiency has become popular where the need has arisen to perform costly investigations which indicate functional deficiency of vitamin B12 even when vitamin B12 levels are normal. These factors pose a challenge in planning management of patients. Aims and objectives : The study was conducted as an attempt to identify affordable and credible laboratory indicators of vitamin B12 deficiency which can be used as screening tests before choosing patients for further evaluation or treatment. Material and Methods : This was a time bound cross-sectional study where 100 adult patients who had undergone the following investigations were randomly chosen: Complete Blood Count with red cell indices, serum bilirubin and serum vitamin B12 levels. The sensitivity, specificity and predictive values (positive-PPV and negative-NPV) of the variables that could hypothetically identify vitamin B12 deficiency, both individually or in combinations were calculated and compared. Results and conclusion : Hemoglobin, MCV (Mean Corpuscular Volume), MCH (Mean Corpuscular Hemoglobin), platelets and bilirubin were not equally distributed between vitamin B12 deficient and normal groups(p values for these variables were 0.029, 0.000, 0.000, 0.003 and 0.029 respectively).When these variables were tested individually and in combination, the combination of [MCV=95 fl or MCH=30 pg or Platelets =1.4 lakh/µl or Bilirubin =1 mg/dl] had sensitivity of 68.2%, specificity of 85.7%, PPV of 78.9% and NPV of 77.4%. This proposed combination used as a screening test has potential for wide application considering its simplicity and cost advantage.

Introduction : Prevalence of vitamin B12 deficiency is believed to increase with aging. The wide and non-specific spectrum of clinical presentations in patients poses a tough challenge to physicians suspecting vitamin B12 deficiency. Objectives : This study was conducted to collect data on prevalence and clinical features of vitamin B12 deficiency in apparently healthy elderly population visiting hospitals, as the results could help rationalize and direct the appropriate management of vitamin B12 status in elderly. Methods : This was a time bound cross sectional study where apparently healthy individuals >50 years of age were interviewed, examined and investigated in order to study their vitamin B12 concentrations and associated clinical profile. Results: A total of 103 participants were included. The mean vitamin B12 level of the study population was 327.07 pg/ml (S.D= 268.00). In the study, 43.7% (n=45 patients) had low vitamin B12 levels (vitamin B12 deficiency) and 17.5 % (n=18 patients) had subnormal vitamin B12 levels. Among all the symptoms recorded neurological followed by cardiovascular symptoms were more commonly recorded in the patients with vitamin B12 deficiency. Distal dysesthesia was more commonly present in patients with deficient (p 0.044) than in patients with normal vitamin B12 levels. Ataxia and Romberg’s sign positivity were more common in patients with vitamin B12 deficiency when compares to normal vitamin B12 levels (p 0.002 and 0.006, respectively). Conclusion: The study shows that vitamin B12 deficiency is a common problem among elderly and the treating physician should have high index of suspicion when they present with neurological complaints.

Abstract Autoimmune polyglandular syndromes (APS) are rare disorders characterized by auto‐destruction of endocrine and non‐endocrine organs by organ‐specific antibody‐directed T‐lymphocytic infiltration. This case highlights a 29‐year‐old Caucasian man with vitiligo found to have significant neurological abnormalities in the setting of newly diagnosed pernicious anemia and thyroid autoimmune disease.

Background: Current guidelines prioritize monitoring and managing cobalamin (Cbl) deficiency but insufficiently address the issue of functional Cbl deficiency (decreased Cbl sensitivity). This study aims to investigate the prevalence burden of functional Cbl deficiency and to examine its prospective association with mortality risk, compared to Cbl deficiency, among United States (US) adults., Method: The cohort study included 22,513 US participants aged ≥20 years from 1999 to 2014 and was followed up through December 31, 2019. Cbl sensitivity was assessed using a combination of binary classifications for Cbl and methylmalonic acid (MMA) levels, with cutoff values set at 400 pg/mL for Cbl and 250 nmol/L for MMA. Functional Cbl deficiency was defined as elevated MMA and Cbl levels. Serum Cbl levels <148 pmol/L (200 pg/mL) were classified as Cbl deficiency., Results: In this study, approximately 2.1% of US adults had Cbl deficiency, while the age-adjusted prevalence of functional Cbl deficiency was 4.5%, corresponding to an estimated 10 million US adults. Over a median follow-up period of 10.7 years, there were 4636 recorded deaths. Compared to the MMA low Cbl low group (MMA ≤250 nmol/L, Cbl ≤400 pg/mL), the multivariable-adjusted hazard ratios for all-cause, cardiovascular, and cancer-related mortality in the MMA high Cbl high group were 1.76 (95% confidence interval [CI]: 1.53-2.02, p  < 0.001), 2.17 (95% CI: 1.78-2.67, p  < 0.001), and 1.38 (95% CI: 0.95-2.00, p  = 0.089). In contrast, the mortality risk associated with Cbl deficiency became insignificant after adjusting for similar confounders. While Cbl supplementation or dietary intake above recommended levels might alleviate Cbl deficiency, they do not appear to reduce the prevalence of functional Cbl deficiency or its associated mortality risk., Conclusion: Compared with Cbl deficiency, functional Cbl deficiency is more frequent and is significantly associated with increased mortality risk in the general population.

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., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests., (© EFIM 2024.)

Acquired vitamin B12 (vB12) deficiency (vB12D) of newborns is relatively frequent as compared with the incidence of inherited diseases included in newborn screening (NBS) of different countries across the globe. Infants may present signs of vB12D before 6 months of age with anemia and/or neurologic symptoms when not diagnosed in asymptomatic state. The possibility of identifying vitamin deficient mothers after their pregnancy during the breastfeeding period could be an additional benefit of the newborn screening. Vitamin supplementation is widely available and easy to administer. However, in many laboratories, vB12D is not included in the national screening program. Optimized screening requires either second-tier testing or analysis of new urine and blood samples combined with multiple clinical and laboratory follow ups. Our scope was to review the physiologic fate of vB12 and the pathobiochemical consequences of vB12D in the human body. Particular emphasis was put on the latest approaches for diagnosis and treatment of vB12D in NBS.

Iron deficiency is known to aggravate the prognosis of patients with heart failure. Iron has functions in the mitochondrial respiratory chain. In patients with reduced mitochondrial respiration, the mitochondrial ratio between the level of nicotinamide adenine dinucleotide and its reduced form decreases. Due to the mitochondrial-lysosomal interplay, decreased mitochondrial respiration also leads to inhibition of lysosomal hydrolysis. As a result, cobalamin and iron will be trapped in lysosomes. This will, even if iron and cobalamin have been consumed and absorbed in sufficient amounts, lead to their functional deficiencies.1 Functional iron deficiency can further impede mitochondrial respiration. Increased plasma levels of methylmalonic acid were shown to predict all-cause and cardiovascular mortality in the general population. Treatments targeting mitochondrial and lysosomal function may correct the functional deficiencies and improve prognosis in a subgroup of patients with heart failure, notably those with skeletal muscle wasting. Methylmalonic acid levels may be used for monitoring response to treatment, thereby identifying patients of the subgroup in which disease outcome may improve.

Objective: To evaluate the clinical outcomes at age 1.5 ± 0.5 years of infants with vitamin B12 deficiency identified by newborn screening (NBS).Study Design: Prospective multicenter observational study on health outcomes of 31 infants with vitamin B12 deficiency identified by NBS. Neurodevelopment was assessed by the Denver Developmental Screening Test.Results: In 285 862 newborns screened between 2016 and 2019, the estimated birth prevalence of vitamin B12 deficiency was 26 in 100 000 newborns, with high seasonal variations (lowest in summer: 8 in 100 000). Infants participating in the outcome study (N = 31) were supplemented with vitamin B12 for a median (range) of 5.9 (1.1-16.2) months. All achieved age-appropriate test results in Denver Developmental Screening Test at age 15 (11-23) months and did not present with symptoms characteristic for vitamin B12 deficiency. Most (81%, n = 25) mothers of affected newborns had a hitherto undiagnosed (functional) vitamin B12 deficiency, and, subsequently, received specific therapy.Conclusions: Neonatal vitamin B12 deficiency can be screened by NBS, preventing the manifestation of irreversible neurologic symptoms and the recurrence of vitamin B12 deficiency in future pregnancies through adequate treatment of affected newborns and their mothers. The high frequency of mothers with migrant background having a newborn with vitamin B12 deficiency highlights the need for improved prenatal care. [ABSTRACT FROM AUTHOR]

Abstract Disorders of cobalamin (vitamin B12) metabolism are increasingly recognized in small animal medicine and have a variety of causes ranging from chronic gastrointestinal disease to hereditary defects in cobalamin metabolism. Measurement of serum cobalamin concentration, often in combination with serum folate concentration, is routinely performed as a diagnostic test in clinical practice. While the detection of hypocobalaminemia has therapeutic implications, interpretation of cobalamin status in dogs can be challenging. The aim of this review is to define hypocobalaminemia and cobalamin deficiency, normocobalaminemia, and hypercobalaminemia in dogs, describe known cobalamin deficiency states, breed predispositions in dogs, discuss the different biomarkers of importance for evaluating cobalamin status in dogs, and discuss the management of dogs with hypocobalaminemia.

Introduction:Cobalamin (Cbl) deficient infants are mostly outpatients. Medical literature is very limited concerning infants with severe Cbl deficiency requiring intensive care. The aim of this study was to describe infants requiring intensive care whose health issues were primarily related to Cbl deficiency.Methods:This is a single-center retrospective observational study performed at the pediatric intensive care unit at a children’s hospital. Patients aged 6-24 months with low serum Cbl level coexisting with cytopenia (s) and/or macrocytosis, high levels of iron, ferritin and transferin saturation and whose clinical symptoms necessitating intensive care at diagnosis and resolving after Cbl therapy were included. Infants with chronic diseases and birth asphyxia history were excluded.Results:Seven infants were included in the study. The mean age and Cbl level at presentation was 11±5 months and 50±27 pg/mL, respectively. The presenting complaints were diarrhea, vomiting, difficulty swallowing, seizure, respiratory distress and cyanosis after feeding. Three patients needed mechanical ventilation. Megaloblastic changes were detected in five patients who underwent bone marrow aspiration. Cerebral atrophy was found in six of the patients on cranial imaging. Only one patient developed neurological disability during long-term follow-up.Conclusion:This retrospective study was performed to emphasize the importance of Cbl deficiency in infants requiring intensive care or who had serious deterioration of organ functions. Cbl deficiency in children may lead to life-threatening complications such as respiratory failure or neurological disorders. Prompt diagnosis and immediate treatment may not only be life saving but also improves quality of life in long-term follow-up.

Cobalamin (vitamin B12) deficiency is one of the major factors causing degenerative changes in the nervous system and, thus, various neurological and psychiatric symptoms. The underlying cellular mechanism of this phenomenon is not yet fully understood. An accumulation of senescent astrocytes has been shown to contribute to a wide range of pathologies of the nervous system, including neurodegenerative disorders. This study aimed to investigate whether cobalamin deficiency triggers astrosenescence. After inducing cobalamin deficiency in normal human astrocytes in vitro, we examined biomarkers of cellular senescence: SA-β-gal, p16INK4A, and p21Waf1/Cip1 and performed cell nuclei measurements. The obtained results may contribute to an increase in the knowledge of the cellular effects of cobalamin deficiency in the context of astrocytes. In addition, the presented data suggest a potential causative agent of astrosenescence that has not been proven to date.

We present a 44-year-old male patient with new onset of right focal epilepsy and bilateral hand hypesthesia. Cerebral MRI showed bilateral T2w/DWI hyperintense subcortical lesions in the cingulate gyrus, insula, and amygdala, whereas spinal MRI revealed a cervical posterior column lesion, corresponding to subacute combined degeneration. Laboratory workup revealed a cobalamin deficiency due to type A gastritis, and no evidence of antibodies associated with limbic encephalitis. After sufficient cobalamin substitution, the cerebral and spinal lesions gradually regressed. Our case represents a unique cerebral subcortical MRI lesion pattern in a patient with epilepsy and cobalamin deficiency. Thus, the latter represents an important differential diagnosis for autoimmune encephalitis. [ABSTRACT FROM AUTHOR]

Pernicious anemia (PA) is the most common cause of vitamin B12 (cobalamin) deficiency anemia in the world. It is an autoimmune disease, comprising of salient features of autoimmune chronic atrophic gastritis (CAG) and cobalamin deficiency (CD). Although the anemia was first described as pernicious, it may well be controlled with vitamin B12 replacement. The onset and progression of PA is often insidious. Alternatively, patients may have no anemic symptoms since they become acclimatized to the subtle nature of the disease. Oftentimes, there is a possibility that the underlying disease may be missed unless a full blood count (FBC) is investigated, leading to hindrance in the treatment journey. Diagnostic challenges remain tangible for many practicing clinicians, since there is lack of reliable cobalamin assays to diagnose CD as well as clinical mimics, which simulate many other hematological conditions, such as myelodysplastic syndrome, acute leukemia, sideroblastic anemias, bone marrow failure states, thrombotic microangiopathy, and thromboembolism. Moreover, prompt recognition of the symptoms of CD is also vital, because some neurologic sequalae may become irreversible despite replenishing cobalamin. Herein, we discuss a literature review on the pathophysiology, challenging clinical presentations and diagnostic difficulties of PA. Since the cobalamin replacement therapy for PA is straightforward, it will not be discussed in this review. [ABSTRACT FROM AUTHOR]

Objective: Determine the frequency of vitamin cobalamin deficiency in macrocytic anemia cases reporting at tertiary care hospital. Study Design: Cross Sectional study. Setting: Faculty of Medicine and Allied Medical Sciences, Isra University, Hyderabad, Sindh Pakistan. Period: January 2017 to October 2018. Material & Methods: 450 cases of both genders, diagnosed as macrocytic- megaloblastic anemia were studied for the vitamin Cobalamin levels. Cases were collected through non- probability convenient sampling by inclusion and exclusion criteria. Consenting volunteers were asked for blood sampling. 5 mL blood was taken from ante - cubital fossa. Samples were centrifuged and sera were collected for the estimation of vitamin cobalamin by ELISA - assay kit. Continuous and categorical variables were entered in SPSS (version 21.0) and analyzed by Student t-test and Chi-square test respectively at 95% CI (P ≤ 0.05). Results: Male and female comprised 225 (43.3%) and 294 (56.6%) of 519 subjects. Male to female ratio was noted 1.30:1. MCV, MCH and MCHC show statistically significant difference between male and female (P<0.05). MCV in male was 96.8±9.92 fl vs. 105.5±12.04 fl in female (P=0.0001). Normal cobalamin was noted in 15.2% (n= 79) and any type of cobalamin deficiency was noted in 84.7% (n= 440) (P=0.0001). Conclusion: The present study reports frequency of 84.7% Cobalamin deficiency in macrocytic anemia reporting at Indus Medical College Hospital. Further studies are recommended by the treating physicians. [ABSTRACT FROM AUTHOR]

Nitrous oxide (N 2 O) has been thought to be a harmless recreational substance by public perception, but it has been linked to subacute combined degeneration (SACD) due to induction of a functional vitamin B12 deficiency via oxidation and inactivation of the cobalt ion in its molecular structure. N 2 O has been rising in popularity due to several factors including accessibility, low cost, and low perceived risk, leading otherwise healthy people to develop what used to be a neurological disease experienced by select patient populations with dietary restrictions or medical conditions leading to low levels of vitamin B12. Vitamin B12 plays a crucial role in many cellular processes, and loss of functional vitamin B12 cannot be detected by measuring it directly. Substrates from its metabolic pathways such as homocysteine and methylmalonic acid must be measured to check its functional status. Vitamin B12 deficiency also leads to a hypercoagulable state due to the build-up of homocysteine in the blood. We present the case of a 26-year-old male who had reportedly used N 2 O for six months leading to SACD and a popliteal deep vein thrombosis. The options for treatment are abstaining from substance use and vitamin B12 supplementation; however, full recovery after SACD develops is unlikely and patients may be left with permanent neurological dysfunction from N 2 O use., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Arrowhead Regional Medical Center Institutional Review Board issued approval 24-15. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Lander et al.)

Pancytopenia is a complex medical condition characterized by decreased levels of red blood cells (RBCs), white blood cells (WBCs), and platelets (PLTs). It can arise from impaired production, peripheral destruction, or a combination of both. The causes of pancytopenia range from reversible factors like infections and medication reactions to irreversible conditions. Vitamin B12 deficiency is a notable reversible cause that can take years to manifest in adults due to stored reserves. However, deficiencies caused by impaired absorption, especially due to the lack of intrinsic factors (IFs), can lead to rapid deterioration within two to five years. A healthy 39-year-old male with an athletic lifestyle presented with symptoms such as dizziness, nausea, vomiting, palpitations, and fainting over a few days. These symptoms were preceded by weeks of persistent body aches, headaches, weakness, daily fevers, chills, and night sweats. Vital signs were stable. The physical examination revealed conjunctival pallor and lymphadenopathy in the submandibular and superficial cervical regions. Initial blood tests showed normocytic anemia (Hgb 4.9, MCV 80), leukopenia (2.99), thrombocytopenia (142), and elevated liver enzymes (AST 199, ALT 96, and total bilirubin of 2.04). The peripheral smear showed tear-drop cells and hypochromic cells. The initial impression was hematologic malignancy, including but not limited to leukemia, lymphoma, or myelofibrosis given clinical findings such as B-symptoms like night sweats, neck lymphadenopathy, and subjective daily fever, along with pancytopenia. The patient received a bolus of normal saline and a transfusion of two units of packed RBCs. CT scans of the chest, abdomen, and pelvis showed no adenopathy or splenomegaly. Although initial clinical assessment pointed toward a potential hematologic malignancy, comprehensive testing, including SPEP, reticulocyte count/fraction, serum folate, and serum vitamin B12, revealed only severe vitamin B12 deficiency, with a level of less than 150, with the presence of IF antibodies. Treatment involved intensive in-patient vitamin B12 injections followed by a detailed outpatient regimen. The patient completed a daily dose of vitamin B12 injections for seven consecutive days, followed by weekly injections for the next four weeks. Subsequent laboratory results demonstrated an increase in WBC count to 8.39, Hgb level to 13.2, and PLT count of 249, indicating a continued positive response to the vitamin B12 replacement therapy. In summary, pancytopenia poses a diagnostic challenge that demands careful evaluation of patient data and comprehensive testing. Vitamin B12 deficiency, which encompasses pernicious anemia (PA), is among the reversible factors to consider. This aspect holds significance before opting for more invasive measures like a bone marrow biopsy. Nutritional deficiencies need to be considered first as differentials in pancytopenia, even in the absence of typical signs of vitamin B12 deficiency (like macrocytosis and hypersegmented neutrophils) and in the presence of compelling clinical indications pointing to a hematologic malignancy., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Choi et al.)

Hyperpigmentation is a recognized sign of vitamin B12 deficiency that resolves after vitamin repletion. We present the case of a 58-year-old female with neuropsychiatric symptoms who developed progressive darkening of her hands and feet. A diagnosis of vitamin B12 deficiency secondary to pernicious anemia was made and her symptoms and hyperpigmentation resolved following vitamin repletion. Clinicians should consider vitamin B12 deficiency in the differential diagnosis of palmoplantar hyperpigmentation, as early treatment can avert permanent disability in these patients., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Yakubu et al.)