Polycythemia Vera Masked by Megaloblastic Anemia.

Polycythemia vera (PV) is a chronic myeloproliferative disorder characterized by uncontrolled red blood cell production. Megaloblastic anemia is caused by deficiency of cobalamin (vitamin B12) and/or folate (vitamin B9). While B12 deficiency may be caused by insufficient dietary intake or impairment of its utilization, its association with PV is described without exact knowledge of the physiopathology. We herein report the occurrence of megaloblastic anemia due to Vitamin B12 deficiency in an 85-year-old North African woman patient with PV. This case highlights this atypical presentation of PV and challenges that comes with it causing the delay of diagnosis and the complexity of its diagnosis and treatment. Keywords: megaloblastic anemia, polycythemia vera, association, case report.

Nitrous Oxide-induced Myeloneuropathy Due to Recreational Abuse.

BACKGROUND: The recreational use of nitrous oxide (N2O) has increased in recent years with a noticeable surge in the incidence of nitrous oxide-related myeloneuropathy. OBJECTIVES: To raise awareness of increasing myeloneuropathy due to recreational nitrous oxide misuse in Israel. METHODS: We conducted a case series documenting the clinical and investigative features of eight patients presenting with nitrous oxide-induced myeloneuropathy who were admitted to our departments. RESULTS: Paresthesia was the chief complaint in all patients, with sensory gait ataxia being a common feature, which was often accompanied by Romberg's sign and mild lower limb weakness. Vitamin B12 levels were below the normal range in seven patients, accompanied by elevated homocysteine and methylmalonic acid levels. Magnetic resonance imaging scans revealed hyperintense signals in the dorsal columns of the cervical spine. All patients improved following vitamin B12 injections. CONCLUSIONS: Enhancing awareness, prompting the use of appropriate investigations, and advocating for timely treatment are needed to overcome the risks associated with nitrous oxide misuse.

Characterizing Vitamin B12 Deficiency in Neurology Outpatients: A Retrospective Observational Study.

OBJECTIVES: Clinical manifestations of vitamin B12 deficiency are varied and may result in missed or delayed diagnosis. This investigation explores the diverse clinical manifestations and demographic characteristics of vitamin B12 deficiency in neurology outpatients, aiming to enhance timely diagnosis and outcomes. METHODS: The severity of vitamin B12 deficiency was classified as absolute (≤150 pg/mL) or borderline deficiency (150-300 pg/mL). We conducted a retrospective analysis of 165 outpatients with vitamin B12 deficiency at the department of neurology between May 2020 and May 2021. RESULT: Absolute vitamin B12 deficiency was found in 23.0% of the patients. The most common age range was 50-60 years, the most common cause was vegetarianism, and the most common symptom was headache. Epileptiform symptoms were more likely to occur in younger patients (<20 years old) with vitamin B12 deficiency, whereas psychiatric symptoms were more likely to occur in older patients (>70 years old). Vegetarians, salivation, and nonmegaloblastic anemia were more obvious in patients with absolute vitamin B12 deficiency, whereas headaches often showed borderline B12 deficiency. CONCLUSIONS: The clinical characteristics of vitamin B12 deficiency are complex and nonspecific. The diagnosis should be based on multiple factors.

Vitamin B12 deficiency presenting as neck pain and cervical radiculopathy.

Vitamin B12 is required for the formation of haematopoietic cells and the synthesis of myelin. Deficiency typically presents with fatigue and megaloblastic anaemia. Prolonged deficiency can cause neurological symptoms such as paresthesia, which can progress to subacute combined degeneration of the spinal cord. We describe an unusual presentation of B12 deficiency in a young man who was initially diagnosed and treated for cervical radiculopathy. This case highlights the challenges of diagnosing B12 deficiency in patients with neurologic but without haematologic, abnormalities. While the current incidence of B12 deficiency in developed countries is low, cases are likely to rise with the increased adoption of veganism. Clinicians should be aware of the variable presentations of B12 deficiency because delayed diagnosis and treatment increases morbidity and can cause irreversible neurological deficits.

Macro-B12 and Unexpectedly High Levels of Plasma B12: A Critical Review.

A low total plasma vitamin B12 supports a clinical suspicion of B12 deficiency, while the interpretation of an unexpectedly normal/high level is marred by controversies. Here, we critically review current knowledge on B12 in blood plasma, including the presence of the so-called "macro-B12". The latter form is most often defined as the fraction of B12 that can be removed by precipitation with polyethylene glycol (PEG), a nonspecific procedure that also removes protein polymers and antibody-bound analytes. Plasma B12 includes B12 attached to transcobalamin and haptocorrin, and an increased concentration of one or both proteins almost always causes an elevation of B12. The total plasma B12 is measured by automated competitive binding assays, often incorrectly referred to as immunoassays, since the binding protein is intrinsic factor and not an antibody. An unexpectedly high level of B12 may be further explored using immunological measurements of haptocorrin and transcobalamin (optionally combined with e.g., size-exclusion chromatography). Nonspecific methods, such as PEG precipitation, are likely to give misleading results and cannot be recommended. Currently, the need for evaluation of a high B12 of unknown etiology is limited since other tests (such as measurements of methylmalonic acid) may better guide the diagnosis of B12 deficiency.

New data supporting that early diagnosis and treatment are possible and necessary in intracellular cobalamin depletion: the case of transcobalamin II deficiency.

OBJECTIVES: 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. CASE PRESENTATION: 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. CONCLUSIONS: 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.

Severe Hemolytic Anemia: Atypical Presentation of Cobalamin Deficiency.

Two severe cases of hemolytic anemia are described in different pediatric age groups, both linked to severe cobalamin deficiency from distinct causes. The first case refers to an exclusively breastfed infant with vitamin deficit secondary to maternal impaired absorption. Apart from the neurological deficits present at diagnosis, he also presented with infantile epileptic spasms syndrome a few months after treatment while having normal cobalamin serum levels. The second case refers to an adolescent with long-term inadequate intake. The occurrence of severe hemolytic anemia in cobalamin deficiency is exceptionally rare.

Nitrous oxide induced subacute combined degeneration of the spine cord: A case report.

RATIONALE: In recent years, recreational use of inhaled nitrous oxide (N2O) is on the increase among young people, accompanied by a corresponding rise in reports about its toxicity. Subacute combined degeneration of the spine cord (SCD) is the typical clinical picture of the nervous system disorder caused by N2O intoxication, as a result of metabolic disturbance of vitamin B12. PATIENT CONCERNS, DIAGNOSES, INTERVENTIONS AND OUTCOMES: We report a 28-year-old female of SCD due to prolonged use of N2O, presented with paresthesia and unsteady in walking progressing within 1 month. Symptoms gradually improved with the treatment of intramuscular injections of hydroxocobalamin combined with N2O abstinence, and the patient recovered completely with normal neurological examination after 4 months of follow-up. LESSONS: Clinicians should be aware of the clinical features and pathogenesis of SCD caused by N2O intoxication in order to lead effective treatment as soon as possible. Recreational N2O use should always be considered as an etiology when dealing with patients presented with myelopathy and/or neuropathy suspected of vitamin B12 deficiency.

Not a Laughing Matter: When Nitrous Oxide Causes Functional Vitamin B12 Deficiency.

Subacute combined degeneration (SCD) is an acquired neurologic complication from prolonged vitamin B12 deficiency. As a result of dorsal and lateral spinal cord column degeneration, patients present with a range of neurological symptoms, including paresthesias, ataxia, and muscle weakness. Without prompt treatment, irreversible nerve damage occurs. Here we present a young man who developed progressive ascending paresthesias and lower extremity weakness after escalated nitrous oxide use. This case highlights the importance of considering SCD from nitrous oxide toxicity when patients present with progressive ataxia, paresthesia, and lower extremity weakness.

Vitamin B12 is associated negatively with anemia in older Chinese adults with a low dietary diversity level: evidence from the Healthy Ageing and Biomarkers Cohort Study (HABCS).

OBJECTIVE: The associations between plasma vitamin B12 level and anemia under different dietary patterns in elderly Chinese people are poorly understood. We aimed to examine the associations between plasma vitamin B12 levels and anemia under different dietary patterns in adults aged 65 years and older in nine longevity areas in China. METHODS: A total of 2405 older adults completed a food frequency questionnaire at the same time as a face-to-face interview. The dietary diversity score (DDS) was assessed based on the food frequency questionnaire, with the low DDS group referring to participants with a DDS score ≤ 4 points. Vitamin B12 levels were divided into two groups of high (>295 pg/mL) and low (≤ 295 pg/mL) with the median used as the cut-off point. Sub-analyses were also performed on older adults divided into tertiles of vitamin B12 levels: low (< 277 pg/mL), medium (277-375 pg/mL) and high (> 375 pg/mL) to study the association of these levels with anemia. RESULTS: Six hundred ninety-five (28.89%) of these people were diagnosed with anemia and had a mean age of 89.3 years. Higher vitamin B12 levels were associated with a decreased risk of anemia (multi-adjusted OR, 0.59, [95% CI, 0.45 ~ 0.77] P < 0.001) in older adults with a low DDS, whereas no significant association between vitamin B12 levels and anemia was found in older adults with a high DDS in a full-model after adjustment for various confounding factors (multi-adjusted OR, 0.88, [95% CI, 0.65 ~ 1.19], P = 0.41). CONCLUSION: The relationship between vitamin B12 levels and the prevalence of anemia was significant only when the level of dietary diversity in the older adults was relatively low. The dietary structure of the population should be taken into consideration in combination in order to effectively improve anemia status by supplementing vitamin B12.

A new perspective on vitamin B12 deficiency in rheumatology: a case-based review.

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

Preliminary evaluation of the diagnostic performance of Roche Elecsys® active vitamin B12 versus total vitamin B12 for vitamin B12 deficiency screening.

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

Vitamin B12 deficiency after total gastrectomy for gastric cancer, prevalence, and symptoms: a systematic review and meta-analysis.

PURPOSE: Nutrient deficiency is one of the common complications in patients who undergo gastrectomy, especially those vitamins and minerals absorbed in the stomach or by substances in the gastric juice, such as vitamin B12. Hence, this systematic review and meta-analysis were conducted for the first time to investigate the prevalence of vitamin B12 deficiency and its symptoms in gastric cancer (GC) patients who underwent gastrectomy. METHOD: PubMed, Scopus, Google Scholar, and Web of Science databases were searched to find related studies. After screening, studies were selected based on the abstract and title of related studies. The heterogeneity and inconsistency between studies were evaluated using Cochran's Q, I 2 tests. Egger's test analyzed publication bias for studies. A 95% confidence interval (95% CI) was used to estimate the overall prevalence of vitamin B12 deficiency. RESULTS: Fourteen studies, including 2627 GC patients who underwent surgery, were included in the study. The mean age of the patients in this study was 61.2 ±â€…4.93 years. The pooled estimate of meta-analysis results showed that the prevalence of vitamin B12 deficiency after gastrectomy in patients with GC was 48.8% (95% CI:32.4, 65.2%, I 2 : 98.85, τ 2  = 0.05, Q (13) = 1127.8, P  < 0.001). The most important symptoms were anemia, fatigability, cold feet or legs, numbness, and dizziness. CONCLUSION AND RECOMMENDATION: Vitamin B12 deficiency has a high prevalence among patients who have undergone gastrectomy, and it is necessary to pay enough attention to treating these patients after surgery to prevent its complications.

Evaluation of vitamin B12 values at time of diagnosis in 0- to 36-month-old children with food allergies.

OBJECTIVES: The relationship between food allergies and vitamin B12 deficiency in young children remains unclear despite extensive studies on the nutritional status of affected children. The aim of this study was to compare vitamin B12 levels in children with recently diagnosed food allergies and healthy children ages 0 to 36 mo. METHODS: A retrospective study at Baskent University Hospital analyzed 773 patients ages 0 to 36 mo. Participants were divided into two groups: food allergy and healthy. Vitamin B12 deficiency (<300 ng/mL) was assessed using χ2 tests and regression analyses. RESULTS: The sample comprised 773 children ages 0 to 36 mo, with a mean age of 16 ± 9 mo (range: 1-36). Among the participants, 399 (52%) were healthy children, whereas 374 (48%) had food allergies. The prevalence of vitamin B12 deficiency was higher in children with food allergies (38%) than in healthy children (21%; P < 0.001). According to both univariate and multivariate regression analyses, formula feeding showed a negative association with vitamin B12 deficiency (ß = -0.54; 95% confidence interval [CI], 0.35-0.97; P = 0.038). On the other hand, having allergic diseases (ß = 0.69; 95% CI, 0.30-0.83; P = 0.040) and breastfeeding for <6 mo (ß = 1.35; 95% CI, 1.41-10.50-0.50; P = 0.009) exhibited a positive association with vitamin B12 deficiency. CONCLUSION: Food-allergic children ages 0 to 36 mo were at higher risk for vitamin B12 deficiency. Formula feeding had a protective effect, whereas allergic diseases and breastfeeding for <6 mo were risk factors. Further investigation is needed to understand the underlying mechanisms. Monitoring B12 levels and interventions are crucial for the nutritional well-being of food-allergic children.

A case of functional vitamin B12 deficiency after recreational nitrous oxide use.

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

Evaluation of Neurodevelopmental Screening Test Scores in Children with Vitamin B12 Deficiency.

INTRODUCTION: Vitamin B12 deficiency can lead to hematological findings, neurological symptoms, and neurodevelopmental delay. The aim of this study was to investigate the impact of vitamin B12 deficiency on the neurodevelopment of children. MATERIALS AND METHODS: This study included 89 children aged between 6 and 24 months without any complaints; 44 of these were evaluated in the study group (serum vitamin B12 <300 pg/mL) and 45 in the control group (serum vitamin B12 ≥300 pg/mL). Denver Developmental Screening Test II (DDST-II) and the Social Communication Area Screening Test (SCAST) were evaluated in each participant. RESULTS: The mean vitamin B12 level in the study group was 206.11 ± 9.1 pg/mL, and in the control group, it was 540.65 ± 24.1 pg/mL. When DDST-II results were analyzed, the rate of getting suspicious and abnormal results in the study group was significantly higher compared with the control group (p = 0.001). The rate of the "risky" SCAST results of the cases was found to be statistically significantly higher in the study group than in the control group (p = 0.003). Vitamin B12 values of patients with suspicious or abnormal DDST-II results and with risky SCAST results were found to be statistically significantly lower than those with normal neurodevelopmental screening tests results (p = 0.001 and p = 0.001, respectively). CONCLUSION: Vitamin B12 deficiency can lead to neurodevelopmental delay in children, even in the absence of neurological and hematological symptoms or complaints, which highlights the importance of early detection and intervention of vitamin B12 deficiency.

Coexistence and clinical implications of anemia and depression in the elderly population. / Wspólwystepowanie i implikacje kliniczne anemii i depresji u osób w podeszlym wieku.

Anemia and depression are common in the elderly and they are important medical, social and economic problems for the world. Both disorders are associated with a lower quality of life, multimorbidity and a higher risk of death. The connections between anemia and depression have been reported, but the mechanism and clinical consequences of their co-existence are not fully understood. Several links can be found between anemia and depression in the elderly: common etiological factors, low socioeconomic status of patients, poor education and less physical activity. Both conditions are associated with the occurrence of the same pathological changes: age-related (especially with the presence of inflammation, oxidative stress, degenerative changes in organs and tissues), nutritional deficiencies (iron, vitamin B12, folic acid) and hormonal disorders (especially thyroid gland disorders, sex hormone deficiencies). Anemia and depression are not sufficiently diagnosed in the elderly and, as a result, are often left untreated. The diagnosis and treatments of these conditions in the elderly differ from those in other age groups. The study provides an overview of the literature regarding the co-existence of anemia and depression in elderly patients and clinical recommendations.