Cause Of Cobalamin Deficiency Research Articles

Pernicious anemia is a common cause of cobalamin deficiency-caused megaloblastic anemia in Hainan, China

ABSTRACT Background Pernicious anemia (PA) is believed to be highly prevalent in Western countries but has rarely been reported in China. The study explores whether PA, an autoimmune disease, is an uncommon cause of cobalamin (vitamin B12) deficiency anemia in China. Methods Clinical and hematological data were collected from 90 cobalamin deficiency-caused megaloblastic anemia (MA) patients between July 2014 and December 2021. Through anti-intrinsic factor antibody (IFA) and anti-parietal cell antibody (PCA) testing, PA was distinguished from other causes of cobalamin deficiency leading to MA. Meanwhile, 30 healthy controls (HCs) were included to estimate the positive rates of IFA and PCA. Results Of the 30 HCs, only one tested positive for IFA, and all 30 tested negative for PCA. Among the 90 patients with cobalamin deficiency-caused MA, 76.7% were positive for IFA, and 47.8% were positive for PCA; a total of 76 patients (84.4%) were diagnosed with PA. The mean follow-up time was 41.0 ± 16.3 months. During the follow-up period, no case relapsed among the continuous cobalamin-supply treatment patients, while 24.4% of patients relapsed due to the interruption of maintenance cobalamin-supplement therapy (the median recurrence time was 54.0 ± 17.7 months). Conclusions The proportion of PA in cobalamin deficiency-caused MA patients in Hainan province was higher than 80%, which was more common than expected. Therefore, screening for IFA, PCA, endoscopic biopsy, and thyroid-related parameters are recommended for all cobalamin deficiency-caused MA patients. Furthermore, maintenance cobalamin-supplement therapy is important for PA patients.

A mother's deficiency, a baby's challenge: vitamin B12 deficiency-related seizures and pancytopenia in an infant

Anemia is prevalent in pediatric age and it stems from diverse factors. While iron deficiency is a common cause above six months of age, other nutritional deficits contribute to the disease burden. During pregnancy, anemia due to nutritional deficits is associated with adverse outcomes for the newborn. Precise diagnosis of dietary deficits in the pediatric population is vital to avert negative health consequences. We describe the case of a six-month-old exclusively breastfed infant with a mother having unspecified anemia under folic acid supplementation. The infant presented with neurological symptoms, including paroxysmal events and developmental regression. Laboratory analysis revealed pancytopenia and severe vitamin B12 deficiency. The patient’s mother's serum level of vitamin B12 was also low and ant parietal cell antibodies were positive, suggesting maternal autoimmune gastritis. Treatment with hydroxocobalamin led to clinical and analytical improvement. Maternal deficiency is the major cause of cobalamin deficiency in infants. It is paramount to raise awareness to this issue to prevent its avoidable repercussions.

An Exceptional Case of Cobalamin Deficiency that Presented with Extremely High Indirect Bilirubin Levels

Cobalamin deficiency anemia is a type of anemia that present with weakness, fatigue, icteric sclera and neuropathy. Main causes of cobalamin deficiency are low intake or decreased absorption (gastric and intestinal causes). In present case, we report a 65-year-old male who presented to the emergency department with signs and symptoms of cobalamin deficiency including bilateral peripheral neuropathy, icteric skin and sclera, and abdominal pain in right upper quadrant. He had low cobalamin and extremely high bilirubin levels (8mg/dL) in serum. After the diagnosis of cobalamin deficiency established, 1mg daily cobalamin treatment initiated for five days which would follow weekly and monthly intramuscular injections consequently. Hemolysis and other causes of elevated indirect bilirubin levels were excluded in differential diagnosis. Clinical and laboratory improvements were achieved after the treatment. In conclusion, physicians should kept in mind cobalamin deficiency even in subjects with unusual high levels of indirect bilirubin.

Neurological disorders in vitamin B12 deficiency.

The review discusses thesteps of vitamin B12 metabolism and its role in maintaining of neurological functions. The term "vitamin B12 (cobalamin)" refers to several substances (cobalamins) of a very similar structure. Cobalamin enters the body with animal products. On the peripherу cobalamin circulates only in binding with proteins transcobalamin I and II (complex cobalamin-transcobalamin II is designated as "holotranscobalamin"). Holotranscobalamin is absorbed by different cells, whereas transcobalamin I-binded vitamin B12 - only by liver and kidneys. Two forms of cobalamin were identified as coenzymes of cellular reactions which are methylcobalamin (in cytoplasm) and hydroxyadenosylcobalamin (in mitochondria). The main causes of cobalamin deficiency are related to inadequate intake of animal products, autoimmune gastritis, pancreatic insufficiency, terminal ileum disease, syndrome of intestinal bacterial overgrowth. Relative deficiency may be seen in excessive binding of vitamin B12 to transcobalamin I. Cobalamin deficiency most significantly affects functions of blood, nervous system and inflammatory response. Anemia occurs in 13-15% of cases; macrocytosis is an early sign. The average size of neutrophils and monocytes is the most sensitive marker of megaloblastic hematopoiesis. The demands in vitamin B12 are particularly high in nervous tissue. Hypovitaminosis is accompanied by pathological lesions both in white and gray brain matter. Several types of neurological manifestations are described: subacute combined degeneration of spinal cord (funicular myelinosis), sensomotor polyneuropathy, optic nerve neuropathy, cognitive disorders. The whole range of neuropsychiatric disorders with vitamin B12 deficiency has not been studied well enough. Due to certain diagnostic difficulties they are often regarded as "cryptogenic", "reactive", "vascular» origin. Normal or decreased total plasma cobalamin level could not a reliable marker of vitamin deficiency. In difficult cases the content of holotranscobalamin, methylmalonic acid / homocysteine, and folate in the blood serum should be investigated besides carefully analysis of clinical manifestations.

Thrombotic thrombocytopenic purpura or cobalamin deficiency? A case report and review

Introduction: The classic presentation of cobalamin deficiency consists of a macrocytic anemia with or without neurologic manifestations. A common cause of cobalamin deficiency is pernicious anemia, an autoimmune condition in which anti-intrinsic factor antibodies are present. We present a case of pernicious anemia masked by features consistent with thrombotic thrombocytopenic purpura, as well as a review of similar cases in the literature. Case presentation: A 31 year old male presented to the Emergency Department with symptomatic anemia and altered mental status. Laboratory data was significant for microangiopathic hemolytic anemia and thrombocytopenia. A clinical diagnosis of thrombotic thrombocytopenic purpura was made and plasma exchange was initiated. Due to the lack of improvement with plasma exchange, additional laboratory studies were obtained which showed cobalamin deficiency, intrinsic factor antibodies, and ADAMTS13 levels within normal limits. The patient’s clinical and laboratory status improved with parenteral cobalamin replacement and discontinuation of plasma exchange. Discussion: Severe cobalamin deficiency can present as a severe microangiopathic hemolytic anemia that responds rapidly to cobalamin replacement. Key differentiating considerations from thrombotic thrombocytopenic purpura are markedly elevated lactate dehydrogenase, low reticulocyte count, six-lobed polymorphonuclear white blood cells on the peripheral blood smear, and markedly low serum cobalamin.

Beware of the Ailments of Vitamin B12 Deficiency

Vitamin B12 or cobalamin deficiency is a common problem in adult patients, which is however frequently missed. The most common cause of cobalamin deficiency is the food cobalamin malabsorption syndrome (> 60% of all cases). Neuropsychiatric manifestations can be the presenting and only early sign of cobalamin deficiency even in the absence of hematologic abnormalities. The deficiency can occur despite serum cobalamin levels at low normal values; thus, normal vitamin B12 levels have been revised upward to >350 pg/ml. Early detection and treatment are important to prevent structural and irreversible damage. The causes and ailments of vitamin B12 deficiency are herein overviewed and a diagnostic and therapeutic strategy is outlined.

Serum homocysteine and methylmalonic acid concentrations in Chinese Shar-Pei dogs with cobalamin deficiency

Cobalamin deficiency is suspected to be hereditary in Chinese Shar-Pei dogs (Shar-Peis), and inherited causes of cobalamin deficiency may affect the cellular processing of cobalamin. In humans, a defect of the two main cobalamin-dependent intracellular enzymes (i.e., methionine synthase and methylmalonyl-CoA mutase) may lead to hyperhomocysteinemia and hypermethylmalonic acidemia. The aim of this retrospective study was to evaluate serum homocysteine (HCY) and methylmalonic acid (MMA) concentrations in cobalamin-deficient Shar-Peis and dogs of six other breeds. Serum samples (n=297) from cobalamin-deficient dogs (Shar-Peis, German Shepherd dogs, Labrador Retrievers, Yorkshire Terriers, Boxers, Cocker Spaniels, and Beagles) were analyzed for serum HCY and MMA concentrations. A Fisher’s exact test was used to evaluate if cobalamin deficiency in Shar-Peis is associated with hyperhomocysteinemia.Serum HCY and MMA concentrations were higher in cobalamin-deficient Shar-Peis compared to cobalamin-deficient dogs of the six other breeds (P<0.0001). Hyperhomocysteinemia was associated with cobalamin deficiency in Shar-Peis (P=0.009). In addition, serum HCY and MMA concentrations did not differ between cobalamin-deficient German Shepherd dogs with and without exocrine pancreatic insufficiency (EPI), a potential cause of secondary cobalamin deficiency. These findings suggest that the function of the two intracellular cobalamin-dependent enzymes is impaired in Shar-Peis with cobalamin deficiency.

Undetected vitamin B12 deficiency due to false normal assay results.

Cobalamin metabolism is complex and involves a series of processes any of which, if absent, may lead to cobalamin deficiency. The main causes of cobalamin deficiency are food-cobalamin malabsorption (53%), pernicious anaemia (33%), insufficient nutritional vitamin B12 intake (2%) and post-surgical malabsorption (1%)1,2. Dietary causes of the deficiency are limited to elderly people who are already malnourished or to strict vegetarians while malabsorption occurs in patients suffering from several gastrointestinal conditions3. Vitamin B12 is an important co-enzyme required for tetra-hydrofolate production which itself is necessary for normal DNA synthesis. B12 deficiency, therefore, results in impaired DNA formation. The consequent slowing down of cell division leads to the formation of megaloblastic cells especially of those cells with a rapid turnover such as haematopoietic cells and intestinal epithelial cells1. Although measurement of vitamin B12 levels is the gold standard for the diagnosis of B12 deficiency some reports do exist concerning difficulties in its assay4–8. During the 1970s and 1980s vitamin B12 was measured using a 57Co-based radioisotope; since the 1990s, however, with the introduction of automated analysers, most methods are based on solid-phase competitive chemiluminescence enzyme immunoassays9,10. The principal problems with these more recent assays are caused by the presence of intrinsic factor antibodies and heterophilic antibodies in the test sample. Obviously, this is a significant limitation to B12 assays in pernicious anaemia and raises the need to find more sensitive and specific tests to confirm vitamin B12 deficiency11,12. Despite these specificity restrictions and controversy about sensitivity, measurement of plasma cobalamin is still the gold standard for diagnosing vitamin B12 deficiency and its determination can provide intriguing, but misleading information in clinical practice13.

The Syndrome of Food-Cobalamin Malabsorption: A Personal View in a Perspective of Clinical Practice

This article presents recent findings on cobalamin deficiencies due to food-cobalamin malabsorption or nondissociation of vitamin B12 from its carrier proteins syndrome. These findings might be of interest to medical practitioners. This disorder, for which a definitive consensus on the criteria for diagnosis is not yet available, is the leading cause of cobalamin deficiency in the elderly. In practice, food-cobalamin malabsorption is a diagnosis of exclusion, and requires the deductive elimination of all other causes of cobalamin deficiencies, particularly pernicious anaemia. The causes or associated disorders of food-cobalamin malabsorption are multiple and include gastric pathologies, Helicobacter pylori infections and certain drugs (biguanides and proton pump inhibitors). Depending on the disease aetiology, treatment of food-cobalamin malabsorption involves oral supplementation of doses lower than those required for pernicious anaemia.

Early Diagnosis and Treatment of Cobalamin Deficiency of Infancy Owing to Occult Maternal Pernicious Anemia

We report case of an infant who presented with failure to thrive and developmental delay at 4 months of age. He was diagnosed to have vitamin B12 deficiency and antibodies to intrinsic factor secondary to undiagnosed maternal pernicious anemia. The child was treated with hydroxocobalamin and now at 2 years of age, he is developing and growing within normal range. We review the literature on this rare cause of cobalamin deficiency in infants. We highlight the factors determining the outcome and situations where raised index of suspicion could help in recognizing this preventable cause of developmental delay and learning difficulties.

Vitamin B12 deficiency in a 15-year old boy due to mutations in the intrinsic factor gene, GIF

The discoveries of new genes involved in cobalamin assimilation and metabolism has increased our understanding of the rare inborn errors of cobalamin metabolism (Quadros 2009). The following case documents a compound heterozygote mutation in the gastric intrinsic factor (GIF) gene, with a previously described mutation (c.79+1G>A) and a novel mutation (c.290T>C; M97T) leading to a megaloblastic anaemia in an adolescent.

Prevalence and outcome of anemia after restorative proctocolectomy: a clinical literature review.

Iron and/or vitamin B12 deficiency anemias, which have adverse effects on patients' quality of life, are commonly observed and often overlooked complications after restorative proctocolectomy. We performed a systematic review of publications on the prevalence of anemia as well as on the impact of anemia on a range of clinical, functional, quality of life, and economic outcomes in restorative proctocolectomy patients. This information is important to help healthcare providers through a comprehensive overview to increase awareness about a condition that could require therapy to improve patient healthcare and quality of life. We reviewed the English language publications on the incidence of anemia and its adverse effect after restorative proctocolectomy The United States National Library of Medicine database (MEDLINE), the Excerpta Medica database (EMBASE), the Cochran Library, and the Google search engine were searched for published articles on the prevalence and impact of anemia in post-restorative proctocolectomy surgical patients. The long-term complication most frequently described after RPC is pouchitis. Pouchitis is significantly associated with iron deficiency anemia caused by pouch mucosal bleeding. Other causes are insufficient and/or impaired iron absorption. It has also been observed, however, that restorative proctocolectomy patients with underlying familial adenomatous polyposis rarely develop pouchitis yet show higher rates of iron deficiency anemia compared to those patients with underlying ulcerative colitis. Other causes shown as independent risk factors for iron deficiency anemia in restorative proctocolectomy patients are malignancy, desmoid tumors, and J-pouch configuration. Vitamin B12 deficiency anemia is also common after restorative proctocolectomy. About one-third of restorative proctocolectomy patients show abnormal Schilling test and 5 percent have low referenced serum cobalamin. It has been observed that the degree resection of the terminal-ileum, malabsorption, bacterial overgrowth, and dietary factors are among the known causes of cobalamin deficiency. Folate deficiency has not been reported in restorative proctocolectomy patients. Describing restorative proctocolectomy surgery and its outcomes, in patients without anemia, the quality of life is reported excellent regardless of operative technique. Anemia is not uncommon following restorative proctocolectomy and has been shown to have negative effects on the patient's quality of life and the economy and may substantially increase healthcare costs. The treatment of anemia and its underlying causes is important to improving clinical and economic outcomes.

Update of Food-Cobalamin Malabsorption and Oral Cobalamin Therapy

Cobalamin (vitamin B12) deficiency is particularly common in the elderly (>65 years of age), but is often un- recognized because its clinical manifestations are subtle; however, they are also potentially serious, particularly from a neuropsychiatric and hematological perspectives. In the general population, the main causes of cobalamin deficiency are pernicious anemia and food-cobalamin malabsorption. Food-cobalamin malabsorption syndrome, which has only recently been identified, is a disorder characterized by the inability to release cobalamin from food or its binding proteins. This syndrome is usually caused by atrophic gastritis, related or unrelated to Helicobacter pylori infection, and long-term in- gestion of antacids and biguanides. Management of cobalamin deficiency with cobalamin injections is currently well codi- fied, but new routes of cobalamin administration (oral and nasal) are being studied, especially oral cobalamin therapy for food-cobalamin malabsorption.

An update on cobalamin deficiency in adults

Cobalamin (vitamin B12) deficiency is particularly common in the elderly (>65 years of age), but is often unrecognized because of its subtle clinical manifestations; although they can be potentially serious, particularly from a neuropsychiatric and hematological perspective. In the general population, the main causes of cobalamin deficiency are pernicious anemia and food-cobalamin malabsorption. Food-cobalamin malabsorption syndrome, which has only recently been identified, is a disorder characterized by the inability to release cobalamin from food or its binding proteins. This syndrome is usually caused by atrophic gastritis, related or unrelated to Helicobacter pylori infection, and long-term ingestion of antacids and biguanides. Besides these syndromes, mutations in genes encoding endocytic receptors involved in the ileal absorption and cellular uptake of cobalamin have been recently uncovered and explain, at least in part, the hereditary component of megaloblastic anemia. Management of cobalamin deficiency with cobalamin injections is currently well codified, but new routes of cobalamin administration (oral and nasal) are being studied, especially oral cobalamin therapy for food-cobalamin malabsorption.

Cobalamin Deficiency in Elderly Patients: A Personal View

Cobalamin (vitamin B12) deficiency is particularly common in the elderly (>65 years of age) but is often unrecognized because its clinical manifestations are subtle; however, they are also potentially serious, particularly from a neuropsychiatric and hematological perspective. In the elderly, the main causes of cobalamin deficiency are pernicious anemia and food-cobalamin malabsorption. Food-cobalamin malabsorption syndrome is a disorder characterized by the inability to release cobalamin from food or its binding proteins. This syndrome is usually caused by atrophic gastritis, related or unrelated to Helicobacter pylori infection, and long-term ingestion of antacids and biguanides. Management of cobalamin deficiency with cobalamin injections is currently well documented but new routes of cobalamin administration (oral and nasal) are being studied, especially oral cobalamin therapy for food-cobalamin malabsorption.

Novel and Established Markers of Cobalamin Deficiency: Complementary or Exclusive Diagnostic Strategies

New developments in diagnostic markers and a better understanding of the limitations of traditional diagnostic strategies have allowed diagnosis of earlier stages and atypical forms of cobalamin deficiency. Still, there are no generally accepted guidelines for the definition, diagnosis, treatment, and follow-up of cobalamin deficiency. The new trend toward defining cobalamin deficiency purely on the basis of biochemical test outcomes in the absence of overt clinical signs and symptoms could, however, be problematic and may result in overdiagnosis and overtreatment. Use of metabolic markers for the assessment of cobalamin deficiency allows the demonstration of tissue deficiency, but the establishment of the cause of deficiency should also be part of the diagnostic approach. Four groups of diagnostic tests are currently available and these include total cobalamin and cobalamin fractions (such as holo-transcobalamin), tests of gastrointestinal dysfunction, tests of metabolic function, and different gene tests. Among the available tests, only homocysteine, methylmalonic acid, holo-transcobalamin, and possibly methylcitric acid are considered to be useful in clinical practice to add to cobalamin. Gastrointestinal function tests may identify the cause of cobalamin deficiency, whereas the diagnostic usefulness of genetic testing needs to be evaluated. This article provides an overview of recent developments and a reappraisal of novel and established diagnostic markers for cobalamin deficiency.

Cobalamin-binding proteins in normal and cobalamin-deficient older subjects.

The causes of cobalamin (vitamin B(12)) deficiency in older people are only partly understood. We investigated the role of the cobalamin-binding proteins and tested the hypothesis that low saturated transcobalamin concentration is an early marker of cobalamin deficiency. We measured saturated (holo) and unsaturated (apo) transcobalamin and haptocorrin concentrations in healthy middle-aged volunteers, healthy older volunteers, cobalamin-deficient older volunteers and cobalamin-deficient older patients. Holo and apo concentrations of transcobalamin and haptocorrin were similar in healthy middle-aged and older subjects. Holotranscobalamin concentrations were significantly decreased in cobalamin-deficient subjects but did not differ between healthy volunteers and patients. Furthermore, the relative amount of cobalamin on transcobalamin (i.e. holotranscobalamin/holotranscobalamin + holohaptocorrin) was similar in all four groups. Abnormalities of the cobalamin-binding proteins are not a cause of cobalamin deficiency in the aged. Plasma holotranscobalamin concentration did not differ between stages of cobalamin deficiency in older persons. Therefore, plasma holotranscobalamin is not an early marker of cobalamin deficiency in older people and has no additional value in the diagnostic work-up of reduced plasma cobalamin concentrations in older people.

Predictors of Cobalamin Deficiency in Guatemalan School Children: Diet, Helicobacter pylori, or Bacterial Overgrowth?

ABSTRACTObjectivesThe authors investigated whether low vitamin B12 intake, impaired gastric function, Helicobacter pylori infection, and bacterial overgrowth were risk factors for the high prevalence of cobalamin deficiency observed in Guatemalan children.MethodsThe plasma cobalamin concentration of 556 school children was measured and classified as low, marginal, or adequate. In 60 children from each of these three groups, concentrations of serum methylmalonic acid (MMA), plasma homocysteine, and plasma holotranscobalamin II were measured, and usual dietary B12 intake was estimated. Serum gastrin and pepsinogen I concentrations were measured, and H. pylori and bacterial overgrowth were diagnosed using 13C‐urea and 13C‐xylose breath tests, respectively.ResultsH. pylori infection was present in 83% (144 of 174) of children, and bacterial overgrowth was found in 25% (28 of 113). Children with H. pylori infection had higher serum gastrin and pepsinogen I. There were no significant differences among the plasma cobalamin groups in the prevalence of H. pylori infection, bacterial overgrowth, serum gastrin, or pepsinogen I concentrations. However, there was a significant positive correlation between serum MMA and gastrin concentrations. The average daily consumption of dietary B12 was 5.5 ± 5.2 μg/day, but intakes for 23% of children were &lt;1.8 μg/day. B12 intake from fortified snacks added an additional 0.3 ± 0.2 μg/day. B12 intake was not significantly different among the plasma cobalamin groups, but it was significantly correlated with plasma cobalamin.ConclusionsThe specific cause of cobalamin deficiency in this population remains unclear, but these results suggest that low dietary B12 intake is a risk factor and alterations in gastric secretions may also play a role.

Predictors of cobalamin deficiency in Guatemalan school children: diet, Helicobacter pylori, or bacterial overgrowth?

The authors investigated whether low vitamin B12 intake, impaired gastric function, infection, and bacterial overgrowth were risk factors for the high prevalence of cobalamin deficiency observed in Guatemalan children. The plasma cobalamin concentration of 556 school children was measured and classified as low, marginal, or adequate. In 60 children from each of these three groups, concentrations of serum methylmalonic acid (MMA), plasma homocysteine, and plasma holotranscobalamin II were measured, and usual dietary B12 intake was estimated. Serum gastrin and pepsinogen I concentrations were measured, and and bacterial overgrowth were diagnosed using C-urea and C-xylose breath tests, respectively. infection was present in 83% (144 of 174) of children, and bacterial overgrowth was found in 25% (28 of 113). Children with infection had higher serum gastrin and pepsinogen I. There were no significant differences among the plasma cobalamin groups in the prevalence of infection, bacterial overgrowth, serum gastrin, or pepsinogen I concentrations. However, there was a significant positive correlation between serum MMA and gastrin concentrations. The average daily consumption of dietary B12 was 5.5 +/- 5.2 microg/day, but intakes for 23% of children were <1.8 micro g/day. B12 intake from fortified snacks added an additional 0.3 +/- 0.2 microg/day. B12 intake was not significantly different among the plasma cobalamin groups, but it was significantly correlated with plasma cobalamin. The specific cause of cobalamin deficiency in this population remains unclear, but these results suggest that low dietary B12 intake is a risk factor and alterations in gastric secretions may also play a role.

The patient that changed my practice: A rare case of organic psychosis

Correspondence Address Jaime Moya, Psychiatry Resident, University Clinic, University of Navarra, Avda. Pio XII N8 36 CP: 31080 Pamplona, Navarra, Spain E-mail: jmoya@unav.es This article presents a patient with a history of depression, progressive impairment of brain functions, diarrhoea and faecal incontinence. A cobalamin deficiency, without megaloblastic anaemia was detected, and an abnormal Schilling test not due to intrinsic factor deficiency was obtained. Once other causes of cobalamin deficiency were ruled out, it was considered caused by blind-loop syndrome. Treatment with vitamin B complex and long-term oral antibiotic therapy led to a complete resolution of neurological and digestive symptoms. This case illustrates B12 deficiency as a possible cause of reversible dementia, as well as the importance of considering B12 screening in a patient with a history of gastric surgery. Given the depressive history of the patient, the case also emphasizes the relevance of distinguishing a dementia from the cognitive symptoms of depression. (Int J Psych Clin Pract 2003; 7: 147 /150)