Treatment Of Vitamin B12 Deficiency Research Articles

Vitamin B12 Metabolism: A Network of Multi-Protein Mediated Processes

The water-soluble vitamin, vitamin B12, also known as cobalamin, plays a crucial role in cellular metabolism, particularly in DNA synthesis, methylation, and mitochondrial functionality. Its deficiency can lead to hematological and neurological disorders; however, the manifestation of these clinical outcomes is relatively late. It leads to difficulties in the early diagnosis of vitamin B12 deficiency. A prolonged lack of vitamin B12 may have severe consequences including increased morbidity to neurological and cardiovascular diseases. Beyond inadequate dietary intake, vitamin B12 deficiency might be caused by insufficient bioavailability, blood transport disruptions, or impaired cellular uptake and metabolism. Despite nearly 70 years of knowledge since the isolation and characterization of this vitamin, there are still gaps in understanding its metabolic pathways. Thus, this review aims to compile current knowledge about the crucial proteins necessary to efficiently accumulate and process vitamin B12 in humans, presenting these systems as a multi-protein network. The epidemiological consequences, diagnosis, and treatment of vitamin B12 deficiency are also highlighted. We also discuss clinical warnings of vitamin B12 deficiency based on the ongoing test of specific moonlighting proteins engaged in vitamin B12 metabolic pathways.

Clinical case of funicular myelosis in combination with a concomitant genetic predisposition to folate cycle disorder

Funicular myelosis (sub­acute combined degeneration) is a disease characterized by the development of degeneration of the posterior and lateral cords of the spinal cord. Funicular myelosis is a neurological complication of vitamin B12 deficiency, which occurs as a result of reduced intake of vitamin B12 with food, malabsorption, in connection with taking some drugs (metformin, proton pump inhibitors, and nitrous oxide), with invasion by Diphyllobothrium latum. The disease is usually characterized by the presence of paresthesias, the development of sensitive ataxia, and impaired gait. The aim of the work was to demon­strate a clinical case of funicular myelosis in a young patient in order to improve the diagnostic process, paying attention to the genetic profile and identifying a concomitant predisposition to folate cycle disorder. A clinical case of funicular myelosis in a 39-year-old woman is described. The patient came to the neurology department with complaints of numbness in the upper and lower limbs, periodic shooting pains along the spine when the head is tilted forward. During the neurological examination, the following was observed: a decrease in vibrational, muscle-joint, discrimination sensitivity in the upper limbs, paresthesias in the distal parts of the limbs, and sensitive ataxia. According to the results of the magnetic resonance imaging (MRI) of the spinal cord, a lesion of the posterior cords on the long segment (C2-Th1) was found, which corresponds to the subacute degeneration of the spinal cord, which arose due to the deficiency of holotranscobalamin (active B12). The patient received appropriate treatment and was discharged home. Subsequently, the patient was found to have a concomitant genetic predisposition to folate cycle disorder and the development of thrombophilia. A year later, the woman again came to the neurological department. We carried out a repeated examination, evaluation of the results of the MRI of the cervical spine and other examinations in dynamics. According to the results of the literature analysis, additional markers for the diagnosis of funicular myelosis (in particular, homocysteine), the causes of hyper­homocysteinemia and its effects on the body were described. Timely detection and treatment of vitamin B12 deficiency is quite important, since in severe cases the development of spastic paraplegia is possible. Recovery of lost functions depends on the extent of spinal cord damage and the duration of the disease. If anemia is observed together with neurological symptoms, it is necessary to be especially attentive to possible funicular myelosis and to carry out appropriate diagnostic searches. And when detecting hyperhomocysteinemia, it is advisable to take into account other factors that can cause an increase in the level of homocysteine, in addition to a deficiency of vitamins B6, B12 and folic acid.

A Brief Overview of the Diagnosis and Treatment of Cobalamin (B12) Deficiency.

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

Association of Maternal Vitamin B12 and Folate Levels with Gestational Diabetes Mellitus and Insulin Resistance

Background: The incidence of gestational diabetes mellitus (GDM) has increased in recent decades. Established prevention methods for GDM include diet and exercise. Recent interest has focused on the roles of vitamin B12 and folate in the development of GDM. These micronutrients are essential for one-carbon metabolism, which is involved in many metabolic pathways. However, the study results were conflicting and varied by geographic area. Objectives: The aim of this study was to evaluate the relationship between GDM and vitamin B12 levels in our region. Methods: This case-control study enrolled 180 pregnant women at 24 - 28 weeks of gestation. Half of the participants had GDM, and the other half were healthy individuals. All participants attended outpatient pregnancy care clinics at Shiraz University of Medical Sciences from June 2020 to April 2021. Gestational age, age, and body mass index were matched between the two groups. Vitamin B12, folate, insulin, and homocysteine levels were measured in both groups and insulin resistance was calculated. The results were compared between the two groups, and the relationship between vitamin B12 levels and insulin resistance in each group was investigated. Results: Vitamin B12 deficiency was present in 15.6% of the women with GDM. There were no cases of vitamin B12 deficiency in the control group. The GDM group had lower vitamin B12 levels (365.22 ± 136.82 pg/mL vs. 496.08 ± 156.46 pg/mL, P = 0.001). There was a negative correlation between serum vitamin B12 level and insulin resistance index (P = 0.001, r = -0.62). Folate levels were higher in the GDM group (17.93 ± 3.66 ng/mL vs. 14.60 ± 5.32 ng/mL, P = 0.001), but these levels did not significantly relate to insulin resistance or GDM. Conclusions: In our region, there is a significant relationship between low levels of vitamin B12 and both insulin resistance and GDM, which suggests the need for larger studies and attention to the detection and treatment of vitamin B12 deficiency during pregnancy.

Managing Vitamin B12 deficiency: A Comprehensive Guide

Vitamin B12 represents a group of water soluble vitamin which is necessary for the production of red blood cells and other functions such as DNA synthesis and neurologic functions. Cyanocobalamin is a man-made form of vitamin B12 used to prevent and treat low blood levels of vitamin B12. Most people receive enough vitamin B12 from their diet. However serious vitamin B12 deficiency in some cases may result in a low number of red blood cells (anemia), stomach/intestine problems and permanent nerve damage. B12 deficiency could be seen in certain health conditions such as intestinal/stomach problems, poor nutrition, cancer, HIV infection, pregnancy, old age, alcoholism and in people who follow a strict vegetarian (vegan) diet. Accordingly early diagnosis and treatment of vitamin B12 deficiency is important to avoid any serious health problems. The diagnosis of vitamin B12 deficiency includes both clinical assessment and laboratory tests to ensure an accurate diagnosis and treatment afterward.

Consensus of the Brazilian Association of Nutrology on diagnosis, prophylaxis, and treatment of vitamin B12 deficiency

Introduction: Vitamin B12 deficiency is quite prevalent in all age groups and all regions of the country, however, there is a need for standardization of clinical management recommendations. Objective: It was to achieve a consensus on the diagnosis, prophylaxis, and treatment of vitamin B12 deficiency. Methods: An integrative review of the scientific literature was carried out in Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases and on governmental and regulatory websites. Results: According to the literary search carried out by the authors of this study, 84 scientific works were selected. Based on these findings, in the timeline from 1999 to 2022, randomized controlled clinical studies represented the majority, and prospective and retrospective studies with significant sample sizes were elucidated in this consensus on the vitamin B12 administration for all patient populations. The basis of this scientific evidence was determined by appropriate clinical trials, with additional endpoints including patient clinical symptoms and biochemical parameters in addition to serum and marginal B12 level. Conclusions: Based on the scientific literature, the recommendations of the Brazilian Association of Nutrology for diagnosis, prophylaxis, and treatment of vitamin B12 deficiency were presented.

Subacute Combined Degeneration of Spinal Cord - The Only Manifestation in an Otherwise “Normal” Vitamin B12 Deficient Patient

Sub-acute combined degeneration (SACD) is a myelopathy associated with vitamin B12 deficiency. Vitamin B12 deficiency may be asymptomatic or present with neurological and/or hematological features - neurological features such as myelopathy, neuropathy, dementia/neuropsychiatric abnormalities and rarely optic atrophy commonly presenting at a later stage than hematological changes. We present a case of a 15-year-old female who presented with ataxia, paresthesia and learning disability but no clinical symptoms or hematological evidence suggesting vitamin B12 deficiency. Our case report highlights the importance of early diagnosis and prompt treatment of vitamin B12 deficiency in a patient having only SACD as the disease’s manifestation.

Sublingual spray treatment of vitamin B12 deficiency in children

Objective: Vitamin B12 deficiency can lead to serious health problems both in children and adult. Intramuscular injection therapy is applied as the gold standard in the treatment of vitamin B12 deficiency. There are also oral, nasal, and sublingual spray treatment methods. In this study, we aimed to show the efficacy of sublingual spray treatment of vitamin B12 deficiency in children. Materials and Methods: Forty-five pediatric patients (25 boys, 20 girls), aged 9-36 months with serum cobalamin concentrations less than 200 pg/mL, were treated with sublingual vitamin B12 (methylcobalamin) spray. All patients were treated for four months by giving 500 μg oral spray daily for the first week, every other day for the next one week, two days a week for the next two weeks and then once a week for four months. Vitamin B12 levels were checked after four months. Results: Post-treatment vitamin B12 values were significantly higher than pre-treatment values (p<0.001). Vitamin B12 levels increased from 161.58±32.98 pg/mL to 427.44±148.58 pg/mL. After the treatment, the vitamin B12 level of all patients was found to be >200 pg/mL, except for only two patients. Vitamin B12 levels returned to normal in 96% of the patients with a sublingual spray treatment. Conclusions: Data from this study indicate that sublingual vitamin B12(methylcobalamin) spray (500μg) for four months is effective for treatment of children with vitamin B12 deficiency. Sublingual spray that is easier and more practical to use can be preferred for children with vitamin B12 deficiency instead of parenteral and oral vitamin B12 therapy.

Genel Pediatri Polikliniği Vakalarında B12 Vitamini Eksikliği

Objective: This study aims to determine the frequency of vitamin B12 deficiency in children and how it varies according to age groups. Vitamin B12 is an essential vitamin that has an important role in nucleic acid synthesis, erythrocyte maturation, and nervous system development. Vitamin B12 deficiency commonly causes anemia. However, severe deficiency in children can cause permanent neurological damage. Therefore, early detection and treatment of vitamin B12 deficiency make it possible to prevent its permanent effects. In addition, determining the age groups at risk allows early diagnosis. Material and Method: The study included children aged 0-18 years admitted to anambulatory pediatric outpatient clinic. Serum vitamin B12 values of children were examined. Vitamin B12 levels below 200 pg/mL were considered a deficiency and between 200-300 pg/mL a marginal level. Descriptive methods, Chi-square, and Independent Samples T-Test were used in the statistical analysis of the data. Results: The study evaluated data from 3115 children. 49.6% of the participants were girls, and 50.4% were boys. The mean age was 8.2±5.4 years. The mean serum vitamin B12 level was 436 ± 174 pg/mL. This mean was 442±172 pg/mL in girls and 431±177 pg/mL in boys. Mean vitamin B12 levels did not differ by gender. The frequency of serum vitamin B12 deficiency was 4.1%. However, it was significantly higher in boys than in girls (5.2%-3.0%). The frequency of marginal level was 18.4%. The frequency of vitamin B12 deficiency differed according to age groups. Serum vitamin B12 deficiency was seen at the highest rate between 0-6 months, with 11%. This rate was 7.1% in the 6-24-month group. Conclusion: This study showed the frequency of serum vitamin B12 deficiency in children admitted to anambulatory pediatric outpatient clinic and in certain age groups. In addition, it was seen that vitamin B12 deficiency was common, especially in infancy and adolescence. However, multicenter prospective studies are needed to determine the prevalence and causes of deficiency in a wide area.

Efficiency of the sublingual route in treating B12 deficiency in infants.

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

The Screening and Treatment of Vitamin B12 Deficiency

Vitamin B12 deficiency is now more prevalent than ever. It is a common cause of megaloblastic anemia, neuropsychiatric disorders, and other clinical manifestations. Screening is required in patients with single or multiple risk factors. Measurement of serum methylmalonic acid can be used to confirm deficiency in asymptomatic high-risk patients with low-normal levels of vitamin B12. Oral administration of high-dose vitamin B12 as well as intramuscular administration are effective as corrective therapy. This review briefs about the pharmacokinetics and pharmacodynamics of Vitamin B12, risk factors associated with its deficiency, screening methods and treatment options.

Long-term metformin therapy and vitamin B12 deficiency: An association to bear in mind.

To date, metformin remains the first-line oral glucose-lowering drug used for the treatment of type 2 diabetes thanks to its well-established long-term safety and efficacy profile. Indeed, metformin is the most widely used oral insulin-sensitizing agent, being prescribed to more than 100 million people worldwide, including patients with prediabetes, insulin resistance, and polycystic ovary syndrome. However, over the last decades several observational studies and meta-analyses have reported a significant association between long-term metformin therapy and an increased prevalence of vitamin B12 deficiency. Of note, evidence suggests that long-term and high-dose metformin therapy impairs vitamin B12 status. Vitamin B12 (also referred to as cobalamin) is a water-soluble vitamin that is mainly obtained from animal-sourced foods. At the cellular level, vitamin B12 acts as a cofactor for enzymes that play a critical role in DNA synthesis and neuroprotection. Thus, vitamin B12 deficiency can lead to a number of clinical consequences that include hematologic abnormalities (e.g., megaloblastic anemia and formation of hypersegmented neutrophils), progressive axonal demyelination and peripheral neuropathy. Nevertheless, no definite guidelines are currently available for vitamin B12 deficiency screening in patients on metformin therapy, and vitamin B12 deficiency remains frequently unrecognized in such individuals. Therefore, in this “field of vision” article we propose a list of criteria for a cost-effective vitamin B12 deficiency screening in metformin-treated patients, which could serve as a practical guide for identifying individuals at high risk for this condition. Moreover, we discuss additional relevant topics related to this field, including: (1) The lack of consensus about the exact definition of vitamin B12 deficiency; (2) The definition of reliable biomarkers of vitamin B12 status; (3) Causes of vitamin B12 deficiency other than metformin therapy that should be identified promptly in metformin-treated patients for a proper differential diagnosis; and (4) Potential pathophysiological mechanisms underlying metformin-induced vitamin B12 deficiency. Finally, we briefly review basic concepts related to vitamin B12 supplementation for the treatment of vitamin B12 deficiency, particularly when this condition is induced by metformin.

Comparison of Sublingual and Intramuscular Administration of Vitamin B12 for the Treatment of Vitamin B12 Deficiency in Children

In most countries, contrary to some disadvantages, such as pain, relatively higher cost, and poor adherence to treatment, intramuscular (IM) route is still the primary treatment method for Vitamin B12 (VB12) deficiency. In recent years, because of these difficulties, new treatment methods are being sought for VB12 deficiency. We aimed to compare sublingual (SL) and IM routes of VB12 administration in children with VB12 deficiency and to compare the efficacy of methylcobalamin and cyanocobalamin therapy in these children. This retrospective study comprised 129 patients with VB12 deficiency (serum Vitamin 12 level ≤ 200 pg/mL) aged 5-18 years. Based on the formulations of Vitamin 12, we divided the patients into three treatment groups as IM cyanocobalamin, SL cyanocobalamin, and SL methylcobalamin. After Vitamin 12 therapy, serum Vitamin 12 levels increased significantly in all patients, and there was a statistically significant difference between the treatment groups (p < 0.05). SL cyanocobalamin and methylcobalamin were found as effective as IM cyanocobalamin for children with Vitamin 12 deficiency in correcting serum Vitamin 12 level and hematologic abnormalities.

Cobalamin in the complex treatment and prevention of cognitive impairment

Cognitive impairment (CI) develops not only in structural damage to the central nervous system, but also in encephalopathies of dysmetabolic and deficiency etiology. Recently, special attention is focused on the appearance of CI due to the deficiency of cobalamin (vitamin B12) and folic acid (FA), the change in the level of homocysteine (HC). To detect vitamin B12 deficiency is possible by examining key biomarkers in serum based on a decrease in the levels of vitamin B12 and holotranscobalamin, and levels of methylmalonic acid (MMA) and HC. The article presents an analysis of studies conducted in Norway, Korea, India, and other countries to assess the risks of CI in the presence of reduced levels of vitamin B12 in the elderly, which demonstrated a decrease in brain volume in the elderly (according to MRI data) in combination with altered test parameters that assess cognitive functions. In many studies, female patients with reduced levels of vitamin B12 predominated among the studied patients. Also, some studies have demonstrated the effectiveness of complex CI therapy with the inclusion of vitamin B12 (both for oral and intravenous administration). Oral vitamin B12 therapy at a dose of 1000 μg has been shown to be adequate for the treatment of vitamin B12 deficiency. Also, the administration of vitamin B12 for prophylactic purposes is recommended for patients with subnormal or borderline concentrations of vitamin B12 in the blood serum.

The effects of vitamin B12 deficiency

Vitamin B12 is one of the most important B vitamins. This vitamin has an important role in cellular metabolism and is also associated with folate and vitamin B6 metabolism. Vitamin B12 deficiency occurs as a result of some diseases, the use of certain medications, or inadequate nutrition. It primarily affects the elderly and women, but is also common among the pediatric population. The B12 deficiency mostly affects the functions of the nervous and hematopoietic systems but it can also affect the skin, heart, bones, and eyes. The treatment of vitamin B12 deficiency includes oral or intramuscular vitamin B12 supplementation according to different treatment regimens.

Treatment of vitamin B12 deficiency in elderly decreases the high levels of lipid parameters: A retrospective study

The majority of people around the world experience the effects of the inadequacy of vitamin B12. A cross-sectional study was carried out at the beginning of April to end of December 2019, to examine the impact of vitamin B12 inadequacy and its treatment in improving total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglyceride (TG). The data that contains the levels of vitamin B12, lipid parameters (total cholesterol, LDL, HDL and TG) were gathered from 400 patients (n =400) from various clinical research centres situated in the capital of Jordan, Amman. The patient’s samples were classified into multiple age groups. The data of both total cholesterol and LDL levels were gathered from thirty-five (n=35) patients, their age group is between 55-66 and have begun treatment of vitamin B12 deficiency by intramuscular infusion (1.0 mg) of vitamin B12. Almost 20.5% of the studied individuals (n=400) are found to be vitamin B12 deficient, as the level of vitamin B12 was equal to (&lt;190 ng/ml). The age group (56 - 66) years old was found to have a significant decrease in vitamin B 12 (p&lt; 0.01) and this results was associated with a critical increment in the levels of both total cholesterols (p &lt; 0.01) and LDL p&lt; 0.02) on contrast with other age groups. Our results did not reveal any significant changes in the levels of other lipid parameters in all age groups. Intramuscular injection treatment for thirty days reduces significantly (p&lt; 0.01) the level of vitamin B12. This treatment strategy leads to a decrease in both total cholesterols (p&lt; 0.01) and LDL levels (p&lt; 0.01) substantially.

Elevated Homocysteine after Elevated Propionylcarnitine or Low Methionine in Newborn Screening Is Highly Predictive for Low Vitamin B12 and Holo-Transcobalamin Levels in Newborns.

Early diagnostics and treatment of vitamin B12 deficiency (B12D) in infants, mainly maternally conditioned, is crucial in preventing possible developmental delay and neurological deficits. Currently, B12D is rarely listed in regular newborn screening panels and mostly regarded as an incidental finding. The aim of this study was to evaluate a targeted newborn screening strategy for detection of suspected B12D. A decision strategy based on the primary parameters propionylcarnitine and methionine for selection of samples to be analyzed for total homocysteine by mass spectrometry was established. Therefore, 93,116 newborns were initially screened. Concentrations of vitamin B12 and holotranscobalamin in serum were obtained from clinical follow-up analyses of recalled newborns. Moreover, an extremely sensitive mass spectrometric method to quantify methylmalonic acid from the dried blood spots was developed. Overall, 0.15% of newborns were screened positive for suspected B12D, of which 64% had vitamin B12 concentrations below 148 pM. We also determined a cutoff value for methylmalonic acid in dried blood spots indicative for B12D in infants. Overall, we calculated a prevalence of 92/100,000 for suspected B12D in the Austrian newborns. In conclusion, we present a screening algorithm including second-tier measurement of total homocysteine that allows detection of low B12 serum concentrations with a high detection rate and low false-positive rate.

Role of Pernicious Anemia in Patients Admitted to Internal Medicine with Vitamin B12 Deficiency and Oral Replacement Therapy as a Treatment Option.

To determine the role of vitamin B12 deficiency in pernicious anemia and the efficacy of oral vitamin B12 replacement therapy given regardless of the etiology, and to compare the endoscopic and pathological findings in patients diagnosed with vitamin B12 deficiency. The study included 216 patients, aged 18 - 65 years, diagnosed with vitamin B12 level < 200 pg/mL between May 2015 and May 2016. Evaluation was made of the demographic characteristics of the patients, diseases, drugs used, dietary habits, previous use of vitamin B12 replacement therapy, family history of vitamin B12 deficiency, laboratory test values, and neurological symptoms present at the time of presentation. Endoscopy was applied to all the patients included in the study. Anti-parietal cell antibody (APCA) and anti-intrinsic factor antibody (AIFA) analyses were applied to all patients. Evaluation was made of a total of 216 patients diagnosed with vitamin B12 deficiency, comprising 145 (67.1%) females and 71 (32.9%) males. The mean vitamin B12 level of the patients was determined as 127 pg/mL at the time of presentation and 334 pg/mL after treatment. APCA positivity was determined in 40 (18.5%) patients, and AIFA positivity in 5 (2.3%) patients. Atrophy was determined endoscopically in 53 (24.5%) patients and pathologically in 90 (41.7%). Helicobacter pylori positivity was determined in 196 (90.7%) patients. A diagnosis of pernicious anemia (PA) was made in 4 (1.9%) patients (patients with AIFA positivity or APCA accompanied by corpus atrophy). APCA positivity was determined but not corpus atrophy in 36 (16.7%) patients and these cases were accepted as suspected pernicious anemia. In this study of 216 patients with vitamin B12 deficiency, stomach pathologies which could cause vitamin B12 deficiency (atrophic gastritis, HP, PA) and the responses to oral replacement therapy were investigated. As vitamin B12 absorption plays a role in the pathogenesis. Vitamin B12 deficiency can lead to atrophic gastritis, and this was determined with biopsy in 41.7% of the patients. APCA positivity was determined in 18.5% of the patients investigated with respect to autoimmune atrophic gastritis (pernicious anemia) and AIFA positivity in 2.3%. A diagnosis of PA was made in 4 (1.9%) patients from autoimmune marker positivity and the presence of corpus atrophic gastritis. HP was determined in 90.7% of the patients with vitamin B12 deficiency, and although no correlation was determined between HP and atrophy, HP positivity was determined in 84 (93.3%) of the patients with pathological atrophy. From the time of diagnosis, the patients in the study were prescribed 1,000 µg/day vitamin B12. At the 40-day follow-up examination, a significant increase was observed in the vitamin B12 levels of 92.5% of the patients. At the end of the study, as oral replacement therapy was seen to be effective to a great extent, even in patients with PA, it was concluded that for patients not responding to oral replacement therapy, it would be appropriate to apply parenteral vitamin B12 treatment. In developing countries such as Turkey, the role of HP infection in vitamin B12 deficiency must be kept in mind. The incidence of atrophic gastritis and pernicious anemia is higher than expected in vitamin B12 deficiency. Thus, it can be concluded that it is appropriate to investigate patients with vitamin B12 deficiency with respect to atrophic gastritis and PA, and oral replacement therapy should be the first stage in the treatment of vitamin B12 deficiency.

Investigation of the incidence of vitamin B12 deficiency in leukopenia and neutropenia secondary to infection

Background: Infections and nutritional deficiencies are the most common causes of the leucopenia and neutropenia. In this study, we aimed to find the incidence of vitamin B12 deficiency in patients with leukopenia and neutropenia secondary to infection.Methods: Between September 2018 and December 2018, patients who were referred to Diyarbakır Children Hospital's Pediatric Hematology and Oncology Clinic for leukopenia and/ or neutropenia were thought to develop secondary to infection retrospectively evaluated.Results: Of the 60 patients that evaluated, 23(38.3%) were female and 37(61.7%) were male. The mean age±SD was 4.75±4.5 years. Severe neutropenia was detected in 5(8.3%), moderate neutropenia in 31(51.7%) and mild neutropenia in 17(28.3%) patients. Neutrophil counts were within normal limits in 7(11.7%) patients. When vitamin B12 levels were examined, 17(28.3%) patients had B12 deficiency.Conclusions: Investigation and treatment of vitamin B12 deficiency in patients with leukopenia and neutropenia may shorten the duration of cytopenia and prevent the development of secondary complications.

Newborn Screening for Vitamin B12 Deficiency in Germany—Strategies, Results, and Public Health Implications

To evaluate a systematic newborn screening (NBS) strategy for vitamin B12 deficiency. In a prospective single-center NBS study, a systematic screening strategy for vitamin B12 deficiency was developed and evaluated. Tandem-mass spectrometry screening was complemented by 2 second-tier strategies, measuring methylmalonic/3-OH-propionic/methylcitric acid, and homocysteine from dried blood spots. In a cohort of 176 702 children screened over 27months, 33 children were detected by NBS in whom (maternal) vitamin B12 deficiency was confirmed. Homocysteine was the most sensitive marker for vitamin B12 deficiency, but only combination with a second-tier strategy evaluating methylmalonic acid allowed for detection of all 33 children. Mothers were of various ethnic origins, and 89% adhered to a balanced diet. Treatment in children was performed predominantly by oral vitamin B12 supplementation (84%), and all children remained without clinical symptoms at short-term follow-up. Vitamin B12 deficiency is a treatable condition but can cause severe neurologic sequelae in infants if untreated. The proposed screening strategy is feasible and effective to identify moderate and severe cases of vitamin B12 deficiency. With an incidence of 1:5355 newborns, vitamin B12 deficiency is more frequent than inborn errors of metabolism included in NBS panels. Treatment of vitamin B12 deficiency is easy, and additional benefits can be achieved for previously undiagnosed affected mothers. This supports inclusion of vitamin B12 deficiency into NBS but also stresses the need for increased awareness of vitamin B12 deficiency in caregivers of pregnant women.