Intrinsic Factor Deficiency Research Articles

Oral vitamin B12 supplementation in pernicious anemia: a prospective cohort study

BackgroundThe absorption of vitamin B12 is hindered in pernicious anemia (PA) owing to intrinsic factor deficiency. Traditionally, intramuscular vitamin B12 injections were the standard treatment, bypassing the impaired absorption. Although there is potential for oral vitamin B12 supplementation through passive enteral absorption, it is not commonly prescribed in PA owing to limited studies assessing its efficacy. ObjectivesWe aimed to assess the efficacy of oral vitamin B12 supplementation in PA. MethodsWe enrolled participants diagnosed with incident vitamin B12 deficiency related to PA. The diagnosis of PA was based on the presence of classical immune gastritis and of anti-intrinsic factor and/or antiparietal cell antibodies. To evaluate the vitamin B12 status, we measured total plasma vitamin B12, plasma homocysteine, and plasma methylmalonic acid (pMMA) concentration and urinary methylmalonic acid–to–creatinine ratio. Participants were treated with oral cyanocobalamin at a dosage of 1000 μg/d throughout the study duration. Clinical and biological vitamin B12 deficiency related features were prospectively and systematically assessed over the 1-y study duration. ResultsWe included 26 patients with vitamin B12 deficiency revealing PA. Following 1 mo of oral vitamin B12 supplementation, 88.5% of patients were no longer deficient in vitamin B12, with significant improvement of plasma vitamin B12 [407 (297–485) compared with 148 (116–213) pmol/L; P < 0.0001], plasma homocysteine [13.5 (10.9–29.8) compared with 18.6 (13.7–46.8) μmol/L; P < 0.0001], and pMMA [0.24 (0.16–0.38) compared with 0.56 (0.28–1.09) pmol/L; P < 0.0001] concentrations than those at baseline. The enhancement of these biological parameters persisted throughout the 12-month follow-up, with no patients showing vitamin B12 deficiency by the end of the follow-up period. The median time to reverse initial vitamin B12 deficiency abnormalities ranged from 1 mo for hemolysis to 4 mo for mucosal symptoms. ConclusionsOral supplementation with 1000 μg/d of cyanocobalamin has been shown to improve vitamin B12 deficiency in PA.

Pro- and anti-inflammatory cytokines: the hidden keys to autoimmune gastritis therapy.

Autoimmune gastritis (AIG) is an autoimmune disorder characterized by the destruction of gastric parietal cells and atrophy of the oxyntic mucosa which induces intrinsic factor deficiency and hypo-achlorhydria. AIG predominantly affects the antral mucosa with AIG patients experiencing increased inflammation and a predisposition toward the development of gastric adenocarcinoma and type I neuroendocrine tumors. The exact pathogenesis of this autoimmune disorder is incompletely understood although dysregulated immunological mechanisms appear to major contributors. This review of autoimmune gastritis, an unmet medical need, summarizes current knowledge on pro- and anti-inflammatory cytokines and strategies for the discovery of novel biomarkers and potential pharmacological targets.

Primary Neurologic Symptoms: Have You Considered Pernicious Anemia?

BackgroundVitamin B12, or cobalamin, is a nutrient that is vital for metabolic function. Absorption of ingested B12 is dependent on intrinsic factor, which is secreted by parietal cells within the stomach. Pernicious anemia is caused by an intrinsic factor deficiency or autoantibodies against intrinsic factor. The presence of parietal cell antibodies can destroy parietal cells, which can also lead to a deficiency in intrinsic factor. Both lead to megaloblastic anemia caused by vitamin B12 deficiency. The typical presentation of pernicious anemia includes fatigue, pale appearance, tingling sensation, depression, alterations to vision and smell, urinary incontinence, psychotic episodes, and weakness. The most effective treatment for pernicious anemia is intramuscular B12. Case ReportA 27-year-old woman with a history of vitiligo presented to the emergency department (ED) with bilateral lower extremity weakness, clumsiness, numbness, and tingling. Physical examination revealed ataxia, no sensation below her umbilicus, decreased strength, and hyperreflexia in both lower extremities. Complete blood count in the ED revealed low hemoglobin and hematocrit and elevated mean corpuscular volume, concerning for pernicious anemia. Further laboratory testing upon inpatient admission revealed a low vitamin B12 level and parietal cell antibodies in the blood. The patient's pernicious anemia was treated with intramuscular vitamin B12 injections, which led to near complete resolution of her symptoms. Why Should an Emergency Physician Be Aware of This?Early suspicion and detection of pernicious anemia in the ED can prevent serious and permanent hematologic and neurologic damage and the development of other autoimmune disorders.

Pernicious Anemia: The Hematological Presentation of a Multifaceted Disorder Caused by Cobalamin Deficiency.

Pernicious anemia is still a neglected disorder in many medical contexts and is underdiagnosed in many patients. Pernicious anemia is linked to but different from autoimmune gastritis. Pernicious anemia occurs in a later stage of autoimmune atrophic gastritis when gastric intrinsic factor deficiency and consequent vitamin B12 deficiency may occur. The multifaceted nature of pernicious anemia is related to the important role of cobalamin, which, when deficient, may lead to several dysfunctions, and thus, the proteiform clinical presentations of pernicious anemia. Indeed, pernicious anemia may lead to potentially serious long-term complications related to micronutrient deficiencies and their consequences and the development of gastric cancer and type 1 gastric neuroendocrine tumors. When not recognized in a timely manner or when pernicious anemia is diagnosed with delay, these complications may be potentially life-threatening and sometimes irreversible. The current review aimed to focus on epidemiology, pathogenesis, and clinical presentations of pernicious anemia in an attempt to look beyond borders of medical specialties. It aimed to focus on micronutrient deficiencies besides the well-known vitamin B12 deficiency, the diagnostic approach for pernicious anemia, its long-term complications and optimal clinical management, and endoscopic surveillance of patients with pernicious anemia.

Inherited defects of cobalamin metabolism.

Cobalamin (vitamin B12) is required for activity of the enzymes methylmalonyl-CoA mutase and methionine synthase in human cells. Inborn errors affecting cobalamin uptake or metabolism are characterized by accumulation of the substrates for these enzymes, methylmalonic acid and homocysteine, in blood and urine. Inborn errors affecting synthesis of the adenosylcobalamin coenzyme required by methylmalonyl-CoA mutase (cblA and cblB) result in isolated methylmalonic aciduria; inborn errors affecting synthesis of the methylcobalamin coenzyme required by methionine synthase (cblE and cblG) result in isolated homocystinuria. Combined methylmalonic aciduria and homocystinuria is seen in patients with impaired intestinal cobalamin absorption (intrinsic factor deficiency, Imerslund-Gräsbeck syndrome) and with defects affecting synthesis of both cobalamin coenzymes (cblC, cblD, cblF and cblJ). A series of disorders caused by pathogenic variant mutations affecting gene regulators (transcription factors) of the MMACHC gene have recently been described (HCFC1 [cblX disorder] and deficiencies of THAP11, and ZNF143 [the cblK disorder]).

Intrinsic factor autoantibodies by luminescent immuno-precipitation system in patients with corpus atrophic gastritis

BackgroundCorpus atrophic gastritis (CAG) may lead to intrinsic factor (IF) deficiency and vitamin B12 malabsorption. Intrinsic factor autoantibodies (IFA) are considered markers of pernicious anemia, but their clinical utility in CAG has not been evaluated. This study aimed to assess IFA in CAG patients and controls using a luciferase immunoprecipitation system (LIPS). MethodsRecombinant nanoluciferase-tagged IF secreted from transfected Expi293F cells was used as antigen in an IFA-LIPS assay. IFA IgG were measured in sera from subjects undergoing gastroscopy and biopsy (updated Sydney system) mainly for anemia (57%) or dyspepsia (34%). This cohort comprised 105 patients with histologically-proven-CAG (cases: median age 64 years, 68% females) and 110 subjects with suspected CAG that were histologically negative (controls: median age 67 years, 54% females). Cut-off values were selected by Q-Q-plot analysis (negative: <2.5 arbitrary units). ResultsIFA levels were higher in cases than in controls (Mann-Whitney:p < 10−5). The ROC-AUC was 0.67 (95%CI 0.60–0.73, p < 0.0001). The IFA LIPS sensitivity and specificity for CAG were 32% (95% CI 24–42) and 95% (95% CI 90–99). This diagnostic performance remained similar after stratification for the presence/absence of anemia, dyspepsia or vitamin B12 deficiency. IFA levels were higher in females compared with males (p = 0.0127). In females aged <65 years, IFA-positives were more prevalent than in males (43.5% vs 6.6%, p = 0.011). ConclusionsThe IFA-LIPS assay discriminated between CAG patients and controls showing a good specificity (95%) at the cost of sensitivity (32%). IFA-positivity occurred independently from anemia and vitamin B12 deficiency, but was more frequent in younger females. IFA testing should be considered in patients at high clinical suspicion of CAG.

Hereditary intrinsic factor deficiency in China caused by a novel mutation in the intrinsic factor gene\u2014a case report

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

Coagulation assessment with thromboelastography during abdominal endovascular aneurysm repair in a patient with hemophilia A

BackgroundAs both APTT and APTT-based coagulation method cannot distinguish heparin effect from intrinsic coagulation factor deficiency, we implemented thromboelastography (TEG) for the coagulation assessment in a patient with hemophilia A undergoing an endovascular surgery with heparinization.Case presentationA 68-year-old male with hemophilia A underwent endovascular aortic repair for abdominal aortic aneurism. TEG results showed recovery of coagulation time (R) in both kaolin assay (CK) and kaolin-heparinase assay (CKH) after factor VIII replacement before heparinization. Against our expectations, R-CKH was slightly prolonged (9.0 min) during heparinization. After the administration of protamine sulfate, R in both assays showed similar values within the normal ranges.ConclusionsThe combination of CK and CKH assays could be useful to estimate factor VIII (FVIII) level when heparin concentration is low or without heparin; however, caution should be necessary for estimation of FVIII level by TEG under the effect of medium- or high-dose heparin.

Pernicious Anaemia: Mechanisms, Diagnosis, and Management

Pernicious anaemia (PA) is an autoimmune disease of multifactorial aetiology involving environmental and immunological factors. It is the most common cause of cobalamin deficiency anaemia worldwide. The disease is a macrocytic anaemia caused by a vitamin B12 deficiency, which, in turn, is the result of intrinsic factor deficiency, a protein that binds avidly to dietary vitamin B12 and promotes its transport to the terminal ileum for absorption. Despite the advances in understanding the pathogenesis and molecular biology, diagnosis of PA is still challenging for clinicians because of its complexity, diverse clinical presentations, and the limitations of the available diagnostic tools for the evaluation of cobalamin status and the presence of chronic autoimmune atrophic gastritis. Asymptomatic autoimmune gastritis, a chronic inflammatory disease of the gastric mucosa, precedes the onset of corpus atrophy by 10–20 years. Diagnostic dilemmas could occur when patients with PA present with spuriously normal or high cobalamin levels, normocytic or microcytic anaemia, nonanaemic macrocytosis, autoimmune haemolytic anaemia, pseudo-thrombotic microangiopathy, hyperhomocysteinemia-associated thromboembolism, pseudoleukemia, bone marrow failure, and neurologic manifestations without anaemia or macrocytosis. Other autoimmune disorders, especially thyroid disease, Type 1 diabetes mellitus, and vitiligo, are also commonly associated with PA. The present review focusses on novel aspects regarding the pathogenesis, clinical presentation, and the diagnostic approach of PA; the true usefulness of serum vitamin B12 levels; and the risk of adenocarcinoma and gastric carcinoids as well as their treatment and monitoring strategies.

Pernicious Anaemia: Mechanisms, Diagnosis, and Management

Pernicious anaemia (PA) is an autoimmune disease of multifactorial aetiology involving environmental and immunological factors. It is the most common cause of cobalamin deficiency anaemia worldwide. The disease is a macrocytic anaemia caused by a vitamin B12 deficiency, which, in turn, is the result of intrinsic factor deficiency, a protein that binds avidly to dietary vitamin B12 and promotes its transport to the terminal ileum for absorption. Despite the advances in understanding the pathogenesis and molecular biology, diagnosis of PA is still challenging for clinicians because of its complexity, diverse clinical presentations, and the limitations of the available diagnostic tools for the evaluation of cobalamin status and the presence of chronic autoimmune atrophic gastritis. Asymptomatic autoimmune gastritis, a chronic inflammatory disease of the gastric mucosa, precedes the onset of corpus atrophy by 10–20 years. Diagnostic dilemmas could occur when patients with PA present with spuriously normal or high cobalamin levels, normocytic or microcytic anaemia, nonanaemic macrocytosis, autoimmune haemolytic anaemia, pseudo-thrombotic microangiopathy, hyperhomocysteinemia-associated thromboembolism, pseudoleukemia, bone marrow failure, and neurologic manifestations without anaemia or macrocytosis. Other autoimmune disorders, especially thyroid disease, Type 1 diabetes mellitus, and vitiligo, are also commonly associated with PA. The present review focusses on novel aspects regarding the pathogenesis, clinical presentation, and the diagnostic approach of PA; the true usefulness of serum vitamin B12 levels; and the risk of adenocarcinoma and gastric carcinoids as well as their treatment and monitoring strategies.

Autoimmune Gastritis.

Autoimmune gastritis (AG) is a corpus-restricted chronic atrophic gastritis associated with intrinsic factor deficiency, either with or without pernicious anemia. Autoimmune gastritis is a microscopic disease because patients present with no or vague symptoms, and clinicians rarely find endoscopic changes. Autoimmune gastritis only becomes a clinical disease when pathologists diagnose it in gastric biopsies performed for a variety of clinical indications. Unfamiliarity with this disease can result in misdiagnosis of patients, and thus inadequate patient management. To review the pathogenesis, clinical features, diagnostic criteria, differential diagnoses, sequelae, and surveillance recommendations for AG. The sources of the study include a review of the pertinent literature for AG. Autoimmune gastritis is an important disease characterized by a loss of oxyntic mucosa and presence of metaplastic epithelium and enterochromaffin-like cell hyperplasia. Awareness and proper diagnosis are critical to prevent mismanagement of patients.

The investigation of the positive rate of intrinsic factor antibody and deficiency rate of vitamin B(12) in normal physical examination population

目的观察健康查体人群血清内因子抗体（IFAb）阳性率、维生素B12缺乏率，并分析其与年龄、性别、HGB、RBC、平均红细胞体积（MCV）等的相关性。方法以2015年5−6月北京协和医院健康查体人群共计1 427人为研究对象，采用化学发光免疫学方法，使用Beckman DxI800全自动免疫分析仪及其配套试剂检测上述个体血清IFAb和维生素B12水平，比较查体人群中不同性别、不同年龄个体IFAb阳性（IFAb≥1.2 Au/ml）率和维生素B12缺乏（≤145 ng/L）率的差异与相关性。结果1 427例正常查体人群中，共检出IFAb阳性者66例（4.63%）；≥40岁人群IFAb阳性率显著高于<40岁人群（5.66%对1.48%，χ2=7.46，P=0.006）。≤40岁、40~59岁和≥60岁组维生素B12缺乏率分别为2.22%、2.51%和5.50%（χ2=8.55，P=0.014）。查体人群中男性和女性组IFAb阳性率（5.15%对4.04%，χ2=0.99，P=0.320）和维生素B12缺乏率（3.83%对2.69%，χ2=1.44，P=0.230）差异均无统计学意义。多元线性回归结果显示IFAb阳性者HGB比IFAb阴性者平均低3.05 g/L，但是IFAb对RBC和MCV均无影响。而维生素B12是否缺乏与查体人群的HGB、RBC和MCV均无明显相关性。结论查体人群中IFAb阳性率和维生素B12缺乏率均随着年龄的增长而增加，但维生素B12缺乏的发生晚于IFAb阳性的出现。IFAb阳性与否对HGB有显著影响，可以一定程度上弥补维生素B12检测的局限性。在中、老年人群中开展IFAb和维生素B12水平筛查是必要的。

Association of combined GIF290T>C heterozygous mutation/FUT2 secretor variant with neural tube defects.

Folate and vitamin B12 are needed for the proper embryo-fetal development possibly through their interacting role in the 1-carbon metabolism. Folate fortification reduces the prevalence of complex birth defects, and more specifically neural tube defects (NTDs). GIF and FUT2 are 2 genes associated with the uptake and blood level of vitamin B12. We evaluated GIF and FUT2 as predictors of severe birth defects, in 183 aborted fetuses compared with 375 healthy newborns. The GIF290C allele frequency was estimated to 0.4% in healthy newborns and to 8.1% in NTD fetuses (odds ratio 17.8 [95% confidence interval CI: 4.0-77.6]). The frequency of FUT2 rs601338 secretor variant was not different among groups. The GIF 290C heterozygous/FUT2 rs601338 secretor variant combined genotype was reported in 6 of the 37 NTD fetuses, but not in other fetuses and healthy newborns (P < .0001). This GIF/FUT2 combined genotype has been previously reported in children with congenital gastric intrinsic factor (GIF) deficiency, with respective consequences on B12 binding activity and GIF secretion. In conclusion, a genotype reported in congenital GIF deficiency produces also severe forms of NTD. This suggests that vitamin B12 delivery to neural tissue by the CUBN/GIF pathway could play a role in the neural tube closure mechanisms.

Atrophic Body Gastritis: Clinical Presentation, Diagnosis, and Outcome

Atrophic body gastritis is a chronic disorder characterised by atrophy of the oxyntic glands leading to reduced gastric acid and intrinsic factor secretion. Serological studies reported yearly prevalence and incidence rates between 3–9% and 0–11%, respectively. In atrophic body gastritis, the presence of parietal cells and/or intrinsic factor autoantibodies, and autoimmune diseases, such as autoimmune thyroid disease or Type 1 diabetes mellitus, are often observed. These cases are often diagnosed as autoimmune gastritis. This association has been included as part of the autoimmune polyendocrine syndrome. A frequent clinical presentation of atrophic body gastritis is pernicious anaemia, considered an autoimmune condition, arising from vitamin B12 malabsorption as a consequence of intrinsic factor deficiency. Another presentation may be an otherwise unexplained iron deficiency anaemia, as a result of iron malabsorption and consequence of reduced gastric acid secretion. To date, no universally accepted criteria are available to define autoimmune gastritis and to distinguish this clinical entity from chronic, Helicobacter pylori-driven, multifocal atrophic gastritis. In contrast with the classical perception of a silent condition, patients with atrophic body gastritis may complain of a spectrum of gastrointestinal symptoms, ranging from dyspepsia as early satiety, postprandial fullness, and epigastric pain, to gastro-oesophageal reflux symptoms such as regurgitation and heartburn. The timely diagnosis of atrophic body gastritis is important, as this condition puts patients at an increased risk of gastric cancer and other Type 1 carcinoids that may lead to micronutrient deficiencies crucial for erythropoiesis. The present review provides an update on epidemiological and clinical aspects as well as diagnosis and outcome of the disease.

Methylmalonic Acidemia and Megaloblastic Anemia due to Congenital Intrinsic Factor Deficiency

Methylmalonic Acidemia and Megaloblastic Anemia due to Congenital Intrinsic Factor Deficiency

Usefulness of the second-derivative curve of activated partial thromboplastin time on the ACL-TOP coagulation analyzer for detecting factor deficiencies

Usefulness of the second-derivative curve of activated partial thromboplastin time on the ACL-TOP coagulation analyzer for detecting factor deficiencies

Pernicious anemia: diagnosis and course in Burkina Faso

Pernicious anemia (also known as Biermer disease or anemia, Addison or Addisonian anemia, and Addison-Biermer anemia) is an autoimmune atrophic gastritis responsible for vitamin B12 malabsorption due to a deficiency of intrinsic factor. We report eight cases of pernicious anemia in Burkina Faso, collected over a 44-month period. The three criteria for diagnosis of pernicious anemia were: vitamin B12 deficiency, gastric disease (gastric histology) with presence of anti-intrinsic factor, and/or anti-gastric parietal cell antibodies in serum. All patients had anemia, with a mean hemoglobin level of 8.75 g/100mL. The average mean corpuscular volume (MCV) was 122.1 fL the average mean corpuscular hemoglobin (MCH) 39.3 pg, the mean reticulocyte count 12.069 10(9)/L reticulocytes, and the mean rate of megaloblast marrow cells 17.2%. The serum vitamin B12 level ranged from 35 to 71 pmol/L. Antibodies against intrinsic factor were found in all eight patients. All ABO blood groups were present with a predominance (4 cases) of group O. Endoscopy found a normal fundic mucosa in three patients. Histology showed gastric atrophy and intestinal metaplasia for six patients (85.7%). Under B12 vitamin therapy, the course was favorable in all patients; seven patients also had 10 days of iron therapy. We recommend a gastric biopsy even in the absence of macroscopic gastric lesions on the upper gastrointestinal endoscopy.

Investigation of adverse effects of interactions between herbal drugs and natural blood clotting mechanism.

Throughout the world, herbal medicines are consumed by most of the patients without considering their adverse effects. Many herbal medicines/plant extracts have been reported to interact with the natural blood clotting system. In continuation to this effort, thirty medicinal plant extracts were allowed to interact with citrated human blood and the clotting time was measured after re-calcification in vitro using Lee and White method. The aq. leaf ext. of Syzygium cumini and Camellia sinensis significantly prolonged the clotting time. In response to the prothrombin time and activated partial thromboplastin time tests, the ext. of C. sinensis showed normal APTT and marginally prolonged the PT to 16.7 s (control-15.2 s) while S. cumini showed normal PT but significantly prolonged the APTT to 66.9 s (control-20.7 s). This suggests that, C. sinensis acts on the extrinsic pathway while S. cumini on the intrinsic pathway. There are some common herbal formulations that are frequently used by the patients which contain above plant materials, like, Syzygium cumin in anti-diabetic formulations, while the ext. of C. sinensis is consumed frequently as beverage in many part of the world. Hence, patients having known bleeding tendency or haemophilia disease should take into account the interaction potential of these plants with the natural blood clotting system while taking herbal formulations containing above plants; specially, the patients suffering from intrinsic pathway factor deficiency should keep a limit on the consumption of S. cumini while extrinsic pathway factor deficiency patients should limit C. sinensis. Also, the medical practitioners should consider the patient's food consumption history before doing any major surgical procedures.

Intestinal uptake and transport of vitamin B12-loaded soy protein nanoparticles.

Intestinal absorption of vitamin B12 (VB12) is a major challenge in combating pernicious anemia due to intrinsic factor (IF) deficiency. The aim of this study was to explore the feasibility of using soy protein isolates (SPI) nanoparticles to improve the intestinal transport and absorption of VB12. Three different sized VB12-loaded SPI nanoparticles were produced by modulating preparation conditions using a cold-gelation method. The intestinal uptake and transport mechanisms of SPI nanoparticles for VB12 delivery were investigated and related to particle size. SPI nanoparticles were not cytotoxic to Caco-2 cells and were effectively internalized into the cytoplasm via multiple endocytosis pathways including clathrin- and/or caveolae-mediated endocytosis and macropinocytosis routes. VB12 transport across the Caco-2 cell monolayers was increased to 2-3 times after nanoencapsulation, which was dependent on particle size, in the increasing order of 30 > 100 > 180 nm. Using inhibitor block method, the transport of 30 and 100 nm SPI nanoparticles appeared to be clathrin-mediated transcytosis and macropinocytosis routes. The intestinal transport of VB12, assessed using rodent jejunum in Ussing chambers, was improved up to 4-fold after being encapsulated into 30 nm SPI nanoparticles. The findings suggest that SPI nanoparticles could be a promising carrier to facilitate the oral delivery of VB12.

Frequency of intrinsic factor antibody in megaloblastic anaemia.

To evaluate the presence of intrinsic factor antibody in vitamin B12 deficient patients. Cross-sectional, observational study. Fauji Foundation Hospital, Foundation University Medical College and Armed Forces Institute of Pathology, Rawalpindi, from January 2011 to June 2012. A total of 120 patients of megaloblastic anaemia were selected on the basis of low serum vitamin B12 level. The intrinsic factor antibody tests were performed by ELISA method. The patients were considered positive or negative on the basis of presence or absence of intrinsic factor antibody respectively. The data was analyzed by using SPSS version 14. Pernicious anaemia with intrinsic factor deficiency was found in 13.3% in 120 vitamin B12 deficient patients. The mean age of patients of pernicious anaemia was 41.5 years, with a male to female ratio of 1:2.5. It was relatively more common in older age (17% in age more than 60 years) as compared to other age groups. Frequency of pernicious anaemia in megaloblastic anaemia was 13.3%. The male to female ratio was 1:2.5 and it was relatively more common in age group of more than 60 years.