scholarly journals Holotranscobalamin – An Early Marker for Laboratory Diagnosis of Vitamin B12 Deficiency

2009 ◽  
Vol 03 (01) ◽  
pp. 7
Author(s):  
Wolfgang Herrmann ◽  
Rima Obeid ◽  
◽  

Vitamin B12deficiency is widespread. Among the population groups at risk are older people, vegetarians, pregnant women and patients with renal or intestinal diseases. The neurological symptoms of vitamin B12deficiency are unspecific and can be irreversible. Early detection is therefore important. This article reviews the diagnostic performance of the different laboratory markers for vitamin B12status. Total serum vitamin B12is a relatively insensitive and unspecific biomarker of deficiency that does not reflect recent variations in cobalamin status. Holotranscobalamin (holoTC), the metabolically active portion of vitamin B12, is the earliest laboratory parameter that becomes decreased in case of a vitamin B12negative balance. Concentration of methylmalonic acid (MMA) is a functional vitamin B12marker that will increase when the vitamin B12stores are depleted. Isolated lowering of holoTC shows vitamin B12depletion (negative balance), while lowered holoTC plus elevated MMA (and homocysteine) indicates a metabolically manifested vitamin B12deficiency, although there still may be no clinical symptoms. The diagnostic use of holoTC allows the initiation of therapeutic measures before irreversible neurological damage develops. Because the clinical manifestations of vitamin B12deficiency are unspecific, people at risk should be identified and should regularly test their holoTC with or without MMA.

2018 ◽  
Vol 119 (6) ◽  
pp. 629-635 ◽  
Author(s):  
Sadanand Naik ◽  
Namita Mahalle ◽  
Vijayshri Bhide

AbstractThe prevalence of a sub-clinical vitamin B12 deficiency in the vegetarians is high. Total serum vitamin B12 concentration alone does not reliably reflect vitamin B12 status. Holotranscobalamin (holo-TC) II is a bioactive B12 fraction promoting specific uptake of B12 by cells and the circulating concentration reflects the intake of B12, whereas total homocysteine (tHcy) indicates the metabolic ability. In this study, we investigated the diagnostic value of circulating holo-TC, B12, folate and homocysteine in vegetarians who were at risk of B12 deficiency. B12-related biomarkers were measured in 119 young, healthy graduate vegetarians. None was folate deficient. As per reported definition, half were B12 deficient; 70 % of males and 50 % of females had low plasma holo-TC concentrations; and 92 % of males and half of females had hyperhomocysteinaemia. None had any clinical signs of B12 deficiency. Receiver operating characteristic curve analysis demonstrated similar AUC at the B12 concentration of 100 and 150 pmol/l when holo-TC (0·777 and 0·784) and homocysteine (0·924 and 0·928) were used as variables. Cut-off value of 100 pmol/l resulted in the highest sensitivity of 77·78 % and specificity of 71·05 % with a predictive value of 19·6 pmol/l for holo-TC and a sensitivity of 82·72 % and specificity of 89·7 % with a predictive value of 21·7 µmol/l for homocysteine. The combination of B12, holo-TC and tHcy improves the diagnostic accuracy at these cut-offs, and we suggest that for the young Indian vegetarians the cut-off for plasma B12 and holotrancobalamin is 100 pmol/l and 19·6 pmol/l, respectively, and for homocysteine it is 17·6 (females) and 27 µmol/l (males) for identifying B12 deficiency.


2011 ◽  
Vol 81 (5) ◽  
pp. 328-334 ◽  
Author(s):  
Oya Halicioglu ◽  
Sezin Asik Akman ◽  
Sumer Sutcuoglu ◽  
Berna Atabay ◽  
Meral Turker ◽  
...  

Aim: Nutritional vitamin B12 deficiency in infants may occur because the maternal diet contains inadequate animal products. Clinical presentations of the infants who had nutritional vitamin B12 deficiency were analyzed in this study. Subjects and Methods: Patients with nutritional vitamin B12 deficiency were enrolled in the study between 2003 and 2010. The diagnosis was based on a nutritional history of mothers and infants, clinical findings, hematological evaluation, and low level of serum vitamin B12. Results: Thirty children aged 1 - 21 months constituted the study group. Poverty was the main cause of inadequate consumption of animal products of the mothers. All infants had predominantly breastfed. The most common symptoms were developmental delay, paleness, apathy, lethargy, anorexia, and failure to thrive. Hematological findings were megaloblastic anemia (83.3 %), thrombocytopenia (30 %), and severe anemia (13.3 %). All of the mothers had low serum B12 levels; eight of them had megaloblastic anemia. Conclusion: The unusual clinical manifestations of vitamin B12 deficiency may also be seen apart from neurological and hematological findings. Nutritional vitamin B12 deficiency due to maternal deficiency might be a serious health problem in infants. Therefore, screening and supplementation of pregnant and lactating women to prevent infantile vitamin B12 deficiency should be considered.


2018 ◽  
Vol 7 (10) ◽  
pp. 304 ◽  
Author(s):  
Emmanuel Andrès ◽  
Abrar-Ahmad Zulfiqar ◽  
Khalid Serraj ◽  
Thomas Vogel ◽  
Georges Kaltenbach

The objective of this review is to provide an update on the effectiveness of oral and nasal vitamin B12 (cobalamin) treatment in gastrointestinal (GI) disorders. Relevant articles were identified by PubMed and Google Scholar systematic search, from January 2010 and June 2018, and through hand search of relevant reference articles. Additional studies were obtained from references of identified studies, the Cochrane Library and the ISI Web of Knowledge. Data gleaned from reference textbooks and international meetings were also used, as was information gleaned from commercial sites on the web and data from CARE B12 research group. For oral vitamin B12 treatment, 4 randomized controlled trials (vs. intramuscular), 4 narrative and 4 systematic reviews, and 13 prospective studies fulfilled our inclusion criteria. These studies concerned patients with vitamin B12 deficiency related to: food-cobalamin malabsorption (n = 6), Biermer’s disease (n = 3), veganism or vegetarianism (n = 1), total gastrectomy after Roux-en-Y gastric bypass (n = 2) and Crohn’s disease (n = 1). Four prospective studies include patients with vitamin B12 deficiency related to the aforementioned etiologies, except veganism or vegetarianism. The systematic present review documents that oral vitamin B12 replacement, at a daily dose of 1000 μg (1 mg), was adequate to normalize serum vitamin B12 levels and cure main clinical manifestations related to vitamin B12 deficiency, in GI disorders, and thus, with safety profile. For nasal vitamin B12 treatment, only one preliminary study was available. We conclude that oral vitamin B12 is an effective alternative to intramuscular vitamin B12 (except in patients presenting with severe neurological manifestations). Oral vitamin B12 treatment avoids the discomfort, contraindication (in patients with anticoagulation), and cost of monthly injections.


CNS Spectrums ◽  
2008 ◽  
Vol 13 (S3) ◽  
pp. 7-10 ◽  
Author(s):  
Steven T. DeKosky

Alzheimer's disease (AD) is a progressive disorder in which neurodegeneration begins decades before clinical symptoms appear. Detecting AD during this preclinical phase presents both the enormous challenge of identifying at-risk patients prior to symptom onset and the potential reward of treating patients early enough to prevent or slow disease progression. Given that a 5-year delay in the onset of the clinical manifestations of AD could result in almost a 50% reduction in disease prevalence, early detection of AD is a major focus of clinical research. Several objective, measurable indicators of preclinical and clinical characteristics of AD are currently available or in development. These biomarkers are promising because they promote identification of individuals at risk for AD onset and disease progression; diagnostic accuracy and treatment during the early stages of AD; and the development of disease-modifying therapies that may potentially slow or prevent disease progression during the preclinical phase of AD.


1974 ◽  
Vol 32 (2) ◽  
pp. 219-228 ◽  
Author(s):  
R. C Siddons

1. The development of vitamin B12 deficiency, as indicated by the serum and liver vitamin B12 levels and the excretion of methylmalonic acid, was studied over a 2-year period in baboons (Papio cynocephalus) given a diet deficient in vitamin B12. The effects of partial hepatectomy and the inclusion of either ampicillin or sodium propionate in the diet on the rate of development of the deficiency were also studied.2. The baboons had previously been fed on a mainly vegetarian diet. Their serum vitamin B12 levels were less than 100 ng/l and the mean liver vitamin B12 concentration was 0·56 μ/g. Similar serum and liver vitamin B12 levels were found in baboons given a purified diet supplemented with 1 μg vitamin B12/d, and marked increases in the serum and liver vitamin B12 levels occurred when the daily intake was increased to 2 μg.3. The serum vitamin B12 levels decreased to less than 20 ng/l in all baboons given a vitamin B12-deficient diet.4. The liver vitamin B12 concentration also decreased in all baboons given a deficient diet. At 9 months the lowest levels (0·20 μ/g) were found in partially hepatectomized baboons but subsequently baboons given the diet containing ampicillin had the lowest levels (0·11 μ/g).5. The excretion of methylmalonic acid after a valine load was found to be inversely related to the liver vitamin B12 concentration. In the early part of the study, partially hepatectomized baboons excreted the highest amount but subsequently baboons given a diet containing ampicillin excreted the highest amount.6. Increased formiminoglutamic acid excretion after a histidine load was observed in two baboons given a vitamin B12-deficient diet and in both baboons the liver folic acid concentration was low.7. No haematological or neurological symptoms of the vitamin B12 deficiency were observed.


Neurology ◽  
1998 ◽  
Vol 51 (2) ◽  
pp. 622-624 ◽  
Author(s):  
LaRoy P. Penix

A 45-year-old woman sustained two ischemic cerebral infarctions 16 years after ileal resection for Crohn's disease. Her evaluation showed an elevated random serum homocystine level, a low serum vitamin B12 level, and an increased mean corpuscular volume (MCV) without anemia. A methionine-loading test resulted in a marked increase in the homocystine levels 2, 4, and 6 hours after the load. A Schilling test demonstrated a malabsorption of vitamin B12. Vitamin B12 injections normalized her fasting homocystine level and her MCV. She has had no recurrent strokes during a year follow-up.


1967 ◽  
Vol 113 (496) ◽  
pp. 241-251 ◽  
Author(s):  
R. Shulman

For many years, cases of pernicious anaemia associated with mental symptoms have been described, and interest in these symptoms was renewed following the introduction of liver therapy (Richardson, 1929; Phillips, 1931). Interest later appeared to decline, so that MacDonald Holmes (1956), almost 20 years after the last important clinical review of the subject, could comment with justification that although the cerebral lesions of pernicious anaemia had been recognized for more than a century they were still much less familiar than the lesions which occurred in the spinal cord and peripheral nerves. Since then vitamin B12 deficiency as a cause of mental symptoms has given rise to increasing interest, and this is reflected in recent suggestions that serum vitamin B12 assays should be carried out routinely in psychiatric patients and might be more informative nowadays than the routine Wassermann reaction (Strachan and Henderson, 1965; Hunter and Matthews, 1965).


2019 ◽  
Author(s):  
Jiwei Jiang ◽  
Xiuli Shang

Abstract Background: A number of recent studies have reported subacute combined degeneration (SCD) induced by nitrous oxide (N2O) abuse. However, none have reported the association between the dynamic neuroimaging evolution and clinical manifestations of a patient with N2O-induced SCD. Case presentation: We describe a 24-year-old man who developed SCD with inverted V-sign hyperintensities over the posterior aspect of the spinal cord caused by frequent, excessive N2O inhalation. One month after treatment, his weakness and paresthesia resolved and his serum vitamin B12 level had improved above normal, but the hyperintensities on T2-weighted images had extended horizontally and longitudinally, compared to the initial magnetic resonance images (MRI). Two months after treatment, the patient had some remaining distal limb numbness and normal serum homocysteine level; however, the abnormal signals seen on cervical T2-weighted images had only slightly decreased compared to those seen on the one-month follow-up MRI. The evolution of conventional MRI findings lagged behind the clinical manifestation, suggesting a clinical-radiological dissociation. Conclusions: The clinical-radiological dissociation may have occurred in this case because the T2-weighted imaging did not have sufficient sensitivity to reveal cytotoxic edema. Additionally, the serum vitamin B12 level was not a good indicator of cellular vitamin B12. Clinicians should, therefore, recognize this phenomenon, comprehensively assess the condition of patients with N2O-induced SCD, and avoid terminating treatment based on the resolution of clinical symptoms and serological results.


2006 ◽  
Vol 76 (2) ◽  
pp. 95-99 ◽  
Author(s):  
Sandra Hirsch ◽  
Laura Leiva ◽  
Pía de la Maza ◽  
Vivian Gattás ◽  
Gladys Barrera ◽  
...  

Vitamin B-12 deficiency is prevalent among the elderly population but it is often unrecognized because the clinical manifestations are not present. Objective: To evaluate the effects of a nutritional supplement fortified with vitamin B-12 on well nourished, free-living elderly subjects. Patients and methods: Healthy elderly subjects attending two of four clinics were allocated to receive, over six months’ duration, a nutritional supplement with 3.8 µg of vitamin B-12. Subjects attending the other two clinics served as controls. Serum vitamin B-12 levels were measured at baseline and 6 months after the supplementation was started. Results: After 6 months of consuming the supplement fortified with vitamin B-12, serum B-12 concentration increased from 350.1 ± 166.5 pmol/L to 409.0 ± 166.1 and decreased in the control group from 319.4 ± 129.1 to 290.1 ± 135.7 (ANOVA, p < 0.005). Conclusion: A supplementation with 3.8 µg /day of vitamin B-12 led to significant improvements in the serum concentrations of vitamin B-12 in older persons.


Author(s):  
G.S. Dzhambekova ◽  
S. Katsamaki ◽  
V.F. Garib

Молекулярная аллергодиагностика позволяет выявлять сенсибилизацию к большому спектру респираторных аллергенов, что является важным в диагностике аллергической астмы. Более того, на основании IgEреактивного профиля, выявляемого в раннем возрасте, можно прогнозировать развитие аллергических респираторных заболеваний еще на доклиническом этапе. Целью пилотного проекта явилось создание паспорта сенсибилизации школьника с использованием мультиплексной панели для возможности выявления группы риска по развитию астмы у детей раннего школьного возраста. Материалы и методы. Родители 33 учеников, обучающихся во втором классе гимназии города Ташкента, были опрошены по вопроснику ISAAC на наличие клинических проявлений респираторных заболеваний у их детей. Сыворотки крови их детей были протестированы на наличие IgE к различным аллергенным молекулам при помощи исследовательского аллергочипа MeDALL. Результаты. 30 детей были сенсибилизированы как минимум к одному аллергену, и из этого числа 30 родились путем операции кесарева сечения. Всего было распознано 68 аллергенных молекул из 176, расположенных на микрочипе MeDALL. 80 сенсибилизированных детей имели подлинную полисенсибилизацию к 3 и более мажорным аллергенам. У 18 детей были выявлены IgE к бытовым молекулам риска развития астмы, таким как Alt a 1, Bla g 1, Bla g 2, Can f 1, Fel d 1. Заключение. В целом клинические проявления в виде хрипов и обструкции были выявлены у 60 сенсибилизированных детей, но только 40 таких детей находились под наблюдением аллерголога или получали симптоматическое лечение. У 20 уже сенсибилизированных детей клиническая симптоматика отсутствовала. Молекулярное тестирование профиля IgEсенсибилизации и создание аллергопаспорта позволяют определить группу детей с риском развития астмы. Данная информация может быть использована для своевременного назначения терапии и вторичной профилактики астмы уже в ранние школьные годы.Molecular allergy diagnosis allows to identify sensitization to a large range of respiratory allergens, which is important in the diagnosis of allergic asthma. Moreover, based on the reactive IgE profile detected at an early age, it is possible to predict the development of allergic respiratory diseases even at the preclinical stage. The goal of the pilot project was to create a childrens passport sensitization using a multiplex panel to be able to identify groups at risk for the development of asthma in children of early school age. Materials and methods. Parents of 33 students studying in the second grade of the Tashkent gymnasium were questioned using the ISAAC questionnaire for the clinical manifestations of respiratory diseases in their children. Their childrens sera were tested for the presence of IgE to various allergenic molecules using the MeDALL research method. Results. 30 of children were sensitized to at least one allergen, and 30 of them were born by Caesarean section. and 30 of them were born by Caesarean section. In total, 68 of the 176 allergenic molecules located on the MeDALL microchip were recognized. 80 of sensitized children had a genuine polysensitization to 3 or more major allergens. In 18 of children, IgE to household molecules of the risk of developing asthma, such as Alt a 1, Bla g 1, Bla g 2, Can f 1, Fel d 1, were detected. Conclusions. In general, clinical manifestations in the form of wheezing and obstruction were detected in 60 of sensitized children, but only 40 of these children were under the supervision of an allergist or received symptomatic treatment. In 20 of already sensitized children, clinical symptoms were absent. Molecular testing of the profile of IgE sensitization and the creation of an allergic passport allows us to identify a group of children at risk for developing asthma. This information can be used to assign therapy and secondary prevention of asthma in the early school years.


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