Here’s an extensive list of B12 & Pernicious Anemia research references:
Pernicious anemia (also known as Biermer’s disease) is an autoimmune atrophic gastritis, predominantly of the fundus, and is responsible for a deficiency in vitamin B12 (cobalamin) due to its malabsorption. Its prevalence is 0.1% in the general population and 1.9% in subjects over the age of 60 years. Pernicious anemia represents 20%–50% of the causes of vitamin B12 deficiency in adults.Optimal management of pernicious anemia.
Anti-intrinsic factor or anti-parietal gastric cells antibodies were found in 87.5% and 62% of the patients (at least one antibody, in 96%).Update of pernicious anemia. A retrospective study of 49 cases.
It is important to be aware that failure of CBLA assays to detect cobalamin deficiency can occur, especially in cases of pernicious anemia where IF‐blocking antibodies have been implicated in causing assay interference. In addition, early or subclinical cases of cobalamin deficiency may not be detected with current testing platforms and standard reference ranges.Laboratory testing for cobalamin deficiency in megaloblastic anemia.
We describe a case of functional vitamin B12 deficiency where the repeated measurement of a serum B12 level within the normal range led to delay in the diagnosis of subacute combined degeneration of the spinal cord, and possibly permanent neurological damage as a result. Failure of intracellular transport of B12 by transcobalamin-2 can lead to functional B12 deficiency but with apparently normal serum levels, and is suggested by raised levels of either serum methylmalonic acid or homocysteine, associated with low levels of transcobalamin-2. Such patients may respond to repeated high-dose injections of B12.Functional vitamin B12 deficiency.
Two types of autoantibodies to intrinsic factor have been described in the serum of certain patients with pernicious anemia. One type, termed the blocking antibody, inhibits the combination of intrinsic factor and vitamin B12; it can be detected by various technics in approximately 60 percent of patients with pernicious anemia. The second type, binding or precipitating antibody, also interacts with intrinsic factor but does not prevent the subsequent combination of intrinsic factor and vitamin B12, and is present in approximately 30 percent of these patients. The binding autoantibody almost always coexists with the blocking antibody, but not vice versa.The Autoimmune Aspects of Pernicious Anemia.
For practical purposes, the presence of autoantibodies to intrinsic factor represents strong evidence in favor of the diagnosis of pernicious anemia.
Although autoantibody to gastric parietal cell is found in up to 90 per cent of patients with pernicious anemia, this autoantibody is not considered diagnostic of the disease. It is known to occur in 5 to 8 per cent of the random population between the ages of thirty and sixty years and in 14 per cent of women over the age of sixty. Moreover the antibody is present in 60 per cent of patients simple atrophic gastritis and in a variable but significant percentage of patients with thyroid disease. Nonetheless, this antibody is found so frequently in pernicious anemia that its absence should make the clinical suspect another diagnosis.
Steroids are immunosuppressants capable of reversing or retarding certain immune-mediated phenomena. Investigators both in the United States and abroad have clearly demonstrated that administration of steroids to patients with pernicious anemia results in regeneration of the atrophic gastric mucosa with subsequent production of intrinsic factor, that is, steroids appear to reverse the histologic and laboratory evidence of this disease. Furthermore, this therapy can also decrease the titer of serum autoantibodies to intrinsic factor, although the appearance of gastric intrinsic factor appears to precede rather than to coincide with or follow the diminution of serum antibodies. The beneficial effect of steroids, however, has also been observed in patients with pernicious anemia who have no detectable antibodies to intrinsic factor. With discontinuation of steroid therapy the disease state (atrophic gastric mucosa with absent intrinsic factor) recurs. These observations have suggested that immune phenomena may play important roles in the pathogenesis of pernicious anemia; however, other therapeutic properties of steroids, such as their anti-inflammatory activity, might also be responsible for their remarkable effect in this disorder. The effect of steroids is both fascinating and provocative and may well offer a fruitful avenue for further delineation and understanding of the autoimmune mechanisms in pernicious anemia.
Cobalamin (vitamin B12) assays have been central to the diagnosis of clinical cobalamin deficiency such as pernicious anemia because the diagnostic sensitivities of older assays have been approximately 95%. However, the competitive-binding luminescence assay (CBLA) replaced older microbiologic and radioisotope-dilution assays during the past decade. Few studies have compared these methods, and cobalamin CBLA has received less-focused scrutiny than older methods have received in the past.
The diagnostic failures with all three CBLAs suggest widespread CBLA malfunction; The advice becomes untenable when assay failure rates are 22 to 35%. Manufacturers, who have access to proprietary information, must instead transparently identify and permanently correct the defect or defects.Failures of Cobalamin Assays in Pernicious Anemia.
The clinical picture is the most important factor in assessing the significance of test results assessing cobalamin status because there is no ‘gold standard’ test to define deficiency.Guidelines for the diagnosis and treatment of cobalamin and folate disorder.
There is no ideal test to define deficiency and therefore the clinical condition of patients is of the utmost importance.
There is evidence that new techniques such as the measurement of holotranscobalamin and methylmalonic acid levels seem useful in more accurately defining deficiency.
If the clinical features suggest deficiency then it is important to treat patients to avoid neurological impairment even if there may be discordance between the results and clinical features.Vitamin B12 Deficiency.
We can only speculate the reasons behind lack of response to oral vitamin B12 and it may be that cobalamin somehow undergoes a transformation in the portal circulation so is made less able to be internalized by the cells and only when cobalamin is able to bypass portal circulation, the cells internalize it. This seems to be a saturable process since a minority of patients responds clinically to oral therapy.Re: Vitamin B12 Deficiency.
Among 141 consecutive patients with neuro-psychiatric abnormalities due to cobalamin deficiency, we found that 40 (28 percent) had no anemia or macrocytosis.Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis.
We therefore consider that a massive dose methyl vitamin B12 therapy may be useful as an adjunct to immunosuppressive treatment for chronic progressive MS.Vitamin B12 metabolism and massive-dose methyl vitamin B12 therapy in Japanese patients with multiple sclerosis.
Pernicious Anemia primarily affects people of northern European ancestry. It’s rare in children and infants. Onset typically occurs after age 35, and incidence increases with age. It affects about 2% of people older than age 60.Professional Guide to Diseases.
There are too many cases recorded from this hospital and from outside sources who have been treated solely with Vitamin B12 with great success for it to be denied that this substance has a significant influence on the growth rate of neuroblastoma.Neuroblastoma: An Evaluation of Its Natural History and the Effects of Therapy, with Particular Reference to Treatment by Massive Doses of Vitamin B12.
While low serum cobalamin levels do not necessarily imply deficiency, an abnormally high serum cobalamin level forms a warning sign requiring exclusion of a number of serious underlying pathologies. Functional cobalamin deficiency can thus occur at any serum level.The pathophysiology of elevated vitamin B12 in clinical practice.
Vitamin B12 (cobalamin) is a cobalt-containing compound synthesized by bacteria and an essential nutrient in mammals, which take it up from diet. The absorption and distribution of dietary vitamin B12 to the organism is a complex process involving several gene products including carrier proteins, plasma membrane receptors and transporters. Disturbed cellular entry, transit or egress of vitamin B12 may lead to low vitamin B12 status or deficiency and eventually hematological and neurological disorders.Vitamin B12 absorption: mammalian physiology and acquired and inherited disorders.
Pernicious anaemia is an autoimmune atrophic gastritis inducing vitamin B12 deficiency by malabsorption. This disease may be diagnosed in the absence of any anaemia, on a neuropathy or when one or several autoimmune disorders co-exist. Typically, pernicious anaemia is revealed by macrocytic megaloblastic anaemia. Diagnosis is done on low serum vitamin B12, raised serum homocysteine, parietal cell and, intrinsic factor antibodies.Biermer’s disease.
Pernicious anemia is the end stage of type A chronic atrophic (autoimmune) gastritis. The gastritis results in the loss of parietal cells in the fundus and body of the stomach. The loss of these cells is associated with the failure of intrinsic-factor production and results in vitamin B12 deficiency and megaloblastic anemia.
The identification of gastric H+/K+–ATPase as the target of parietal-cell autoantibodies was a major breakthrough in our understanding of the molecular and immunologic basis of autoimmune gastritis. The immunologic mechanisms that allow the initiation and progression of the T-cell response to this enzyme, leading to autoimmune gastritis, remain to be established. Pernicious anaemia is an autoimmune atrophic gastritis inducing vitamin B12 deficiency by malabsorption. This disease may be diagnosed in the absence of any anaemia, on a neuropathy or when one or several autoimmune disorders co-exist. Typically, pernicious anaemia is revealed by macrocytic megaloblastic anaemia. Diagnosis is done on low serum vitamin B12, raised serum homocysteine, parietal cell and, intrinsic factor antibodies.
Combining IFA and PCA testing significantly increases their diagnostic performance for ABG and PA, yielding a 73% sensitivity for PA. The non-invasive combined PCA and IFA assessment may be useful in selecting patients at risk for autoimmune gastritis to be confirmed by gastroscopic-histologic examination.Reassessment of intrinsic factor and parietal cell autoantibodies in atrophic gastritis with respect to cobalamin deficiency
Serum concentrations of vitamin B12 were ultra-high during treatment due to the lack of urinary excretion. After 6 months of treatment, the patients’ pain or paresthesia had lessened, and the ulnar motor and median sensory nerve conduction velocities showed significant improvement. There were no side effects.Intravenous methylcobalamin treatment for uremic and diabetic neuropathy in chronic hemodialysis patients.
The genes and proteins corresponding to all eight complementation groups defined in patients have provided most of the elements required to describe the intracellular processing of vitamin B12 (Fig. 2)Genetic disorders of vitamin B12 metabolism: eight complementation groups – eight genes.
Although all eight genes predicted through complementation analysis have been identified, additional genes are anticipated. Most notably, the mechanism of the mitochondrial transport of B12 remains unknown. The involvement of cblD defects in both the cytosolic and mitochondrial pathways suggests that the MMADHC protein is an accessory to the mitochondrial uptake of vitamin B12.
The discovery that high-dose vitamin B12 can overcome pathway deficits in some patients has given new life to individuals with an otherwise potentially severe or fatal disease. The early discovery that OHCbl is effective in the treatment of cblC disorder while CNCbl is not is a powerful illustration of the complexity of vitamin B12 biochemistry. The more recent finding that AdoCbl or MeCbl may have a significant stabilising effect on MMACHC protein, despite ultimately being hydrolysed to cob(II)alamin, reminds us that there is still much to be learned on behalf of the patient. Strikingly, the most recent success with gene therapy to treat mice with knockout of the Mut gene (Ref. 151) has opened up a new avenue for treatment that might ultimately benefit patients with metabolically ‘unresponsive’ disorders. The application of widespread newborn screening for homocysteine and methylmalonate underscores the opportunity to identify and treat these patients before the onset of potentially irreversible disease.
APCA can be found in 85-90% of patients with PA. Their presence is not sufficient for diagnosis, because they are not specific for PA as they are also found in the circulation of individuals with other diseases. APCA are more prevalent in the serum of patients with T1D, autoimmune thyroid diseases, vitiligo, celiac disease. People with autoimmune diseases should be closely screened for AAG/PA. The anemia develops longitudinally over many years in APCA-positive patients, symptomless, slowly promotes atrophy of the gastric mucosa and parietal cells. APCA are present in 7.8-19.5% of the general healthy adult population. A fraction of these sero-positive people, will never develop AAG or PA. An interesting and not fully explained question is whether APCA presence is related to Helicobacter pylori infection. APCA are found in up to 20.7% of these patients. H. pylori is implicated as one of the candidates causing AAG.Anti-parietal Cell Antibodies – Diagnostic Significance.
Intrinsic factor and parietal cell antibodies are useful surrogate markers of PA, with 73% sensitivity and 100% specificity. PA is mainly considered a disease of the elderly, but younger patients represent about 15% of patients.
PA is frequently associated with autoimmune thyroid disease (40%) and other autoimmune disorders, such as diabetes mellitus (10%), as part of the autoimmune polyendocrine syndrome. PA is the end-stage of ABG. Long-standing Helicobacter pylori infection probably plays a role in many patients with PA, in whom the active infectious process has been gradually replaced by an autoimmune disease that terminates in a burned-out infection and the irreversible destruction of the gastric body mucosa. Human leucocyte antigen-DR genotypes suggest a role for genetic susceptibility in PA. PA patients should be managed by cobalamin replacement treatment and monitoring for onset of iron deficiency.
PA is an often silent and under-diagnosed autoimmune disease, because its onset and progression are very slow and patients may become used to their complaints. Nevertheless, the clinical consequences of undiagnosed PA may be serious, including gastric neoplastic lesions. Thus, gastroenterologists should increase their awareness of this disorder, whose definite histological diagnosis may be preceded by reliable noninvasive serological screening.Pernicious anemia: New insights from a gastroenterological point of view.
Since 1975 cells lines from patients with suspected inborn errors of vitamin B12 metabolism have been referred to our laboratory because of elevations of homocysteine, methylmalonic acid, or both.
The study of highly selected patients with suspected inborn errors of metabolism has consistently resulted in the discovery of previously unknown metabolic steps and has provided new lessons in biology.Lessons in biology from patients with inborn errors of vitamin B12 metabolism.
Cobalamin and holo-transcobalamin II levels are uninformative because they rise with cobalamin influx regardless of therapeutic effectiveness, the extent varying only with the timing in relation to injection.How I treat cobalamin (vitamin B12) deficiency.
Vitamin B12 is of singular interest in any discussion of vegetarian diets because this vitamin is not found in plant foods as are other vitamins. Many of the papers in the literature give values of vitamin B-12 in food that are false because as much as 80% of the activity by this method is due to inactive analogues of vitamin B12.Vitamin B-12: plant sources, requirements, and assay.
No adverse effects have been associated with excess B12 intake from food or supplements in healthy individuals.Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline.
Our results show that ABCD4 colocalizes with the lysosomal proteins LAMP1 and LMBD1, the latter of which is deficient in the cblF defect. Furthermore, we show that mutations altering the putative ATPase domain of ABCD4 affect its function, suggesting that the ATPase activity of ABCD4 may be involved in intracellular processing of vitamin B12.Mutations in ABCD4 cause a new inborn error of vitamin B12 metabolism.
We have shown the ultra-high-dose methylcobalamin (25 mg/day i.m.) slows down the progressive reduction of the CMAP (compound muscle action potential) amplitudes in ALS in the short term (4 weeks). The latencies of SSR (sympathetic skin response) were shorter after treatment (50 mg/day i.v., 2 weeks). In the long-term effect of methylcobalamin (50 mg/day i.m., twice a week), the survival time (or the period to become respirator-bound) was significantly longer in the treated group than in the untreated.Clinical trials of ultra-high-dose methylcobalamin in ALS.
In conclusion, genetic determinants affecting the cellular availability or MTRR-dependent reduction of B12 may increase the risk of spina bifida.Transcobalamin and methionine synthase reductase mutated polymorphisms aggravate the risk of neural tube defects in humans.
Derivatives of vitamin B12 (cobalamin) are essential cofactors for enzymes required in intermediary metabolism. Defects in cobalamin metabolism lead to disorders characterized by the accumulation of methylmalonic acid and/or homocysteine in blood and urine. The most common inborn error of cobalamin metabolism, combined methylmalonic acidemia and hyperhomocysteinemia, cblC type, is caused by mutations in MMACHC. However, several individuals with presumed cblC based on cellular and biochemical analysis do not have mutations in MMACHC. We used exome sequencing to identify the genetic basis of an X-linked form of combined methylmalonic acidemia and hyperhomocysteinemia, designated cblX. A missense mutation in a global transcriptional coregulator, HCFC1, was identified in the index case.An X-linked cobalamin disorder caused by mutations in transcriptional coregulator HCFC1.
Hydroxocobalamin is safe when administered in a 5 gram intravenous dose, and effectively decreases the low whole blood cyanide levels found in heavy smokers.Hydroxocobalamin as a cyanide antidote: safety, efficacy and pharmacokinetics in heavily smoking normal volunteers.
Based on these results we suggest that TC II deficiency due to lack of TC II protein/mRNA in these patients is due to heterogeneous types of nonsense mutations.Nonsense Mutations in Human Transcobalamin II Deficiency.
Juvenile “congenital” pernicious anemia is characterized by vitamin B12 deficiency appearing in early life as the result of a congenital lack of gastric intrinsic factor with no other apparent abnormality of the stomach or its secretions. This is in contrast to the far more frequent adult form of pernicious anemia, in which achlorhydria and gastric atrophy are uniformly present. Furthermore, serum antibodies to intrinsic factor and gastric parietal cells, commonly detected in the adult syndrome, are conspicuously absent in the patients with juvenile “congenital” pernicious anemia.Juvenile Congenital Pernicious Anemia — Clinical and Immunologic Studies.
It was found that in patients with decreased serum folate concentration, urinary excretion of vitamin B12 was increased in a statistically highly significant way.The influence of serum folate on urinary excretion of vitamin B12
Congenital P.A.’s inheritance is thought to be autosomal recessive.CONGENITAL PERNICIOUS ANEMIA: EFFECTS ON GROWTH, BRAIN, AND ABSORPTION OF B12.
Growth retardation and acceleration appeared to be related to B12 deficiency and treatment. I.Q.’s of around 70 in each child may represent the effects of B12 deficiency on cerebral growth. An initial malabsorption of B12 was shown to improve markedly with B12 treatment. In diagnosis of megaloblastic anemia, only that due to B12 deficiency will respond to dosage of 2 to 5 µg B12 (intramuscular) daily. Early diagnosis and treatment may prevent brain damage.
We propose the designation cblG for the mutation in those patients with methylcobalamin deficiency and decreased synthase activity. The results of these studies suggest that the products of at least two loci are required for cobalamin-dependent methionine biosynthesis in mammalian cells.Genetic heterogeneity among patients with methylcobalamin deficiency. Definition of two complementation groups, cblE and cblG.
An increasing variety of hereditary disorders of intracellular cobalamin metabolism, usually first detected because of the presence of methylmalonic aciduria (cblA, cblB, and cblF mutations), homocystinuria (cblE and cblG mutations), or both (cbIC and cblDmutations), have been defined on the basis of complementation studies.Hereditary defect of cobalamin metabolism (cblG mutation) presenting as a neurologic disorder in adulthood.
The incidence of an antibody against gastric parietal cells was determined with an immunofluorescence method in relatives of 21 patients who suffered from pernicious anemia and had the antibody. It was found in 42 out of 220 of these relatives (20 per cent). In a group of 120 patients with pernicious anemia a positive result was obtained in 87 per cent. Three out of 78 allied relatives who were studied as a control group had the parietal cell antibody.A family study of pernicious anemia by an immunologic method.
Eight patients with Addisonian pernicious anaemia were given 20 mg of prednisolone daily for up to 20 weeks. Improvement in absorption of vitamin B12 as judged by the Schilling test occurred in six cases and was pronounced in four, and there was increased secretion of gastric intrinsic factor in four cases. Gastric biopsies showed regeneration of specialized gastric glands in four cases; chief cells were demonstrated histochemically and parietal cells by an immunofluorescent procedure using serum containing parietal cell antibody. There was no correlative change in titre of serum antibody to gastric parietal cells or gastric intrinsic factor. The improved absorption of vitamin B12 was not maintained after prednisolone was stopped, indicating that the regenerated gastric mucosa reverted to the atrophic state. These effects of corticosteroids on gastric function in pernicious anaemia are in keeping with their known capacity to modify damage resulting from antigen–antibody interaction.Prednisolone and gastric atrophy.
The effect of corticosteroids on the gastric mucusa in patients with pernicious anemia is of particular interest in view of the possibility that atrophic gastritis, the primary pathologic lesion in pernicious anemia, may result from destruction of gastric glands by an autoimmune process.The effect of prednisolone on gastric mucosal histology, gastric secretion, and vitamin B 12 absorption in patients with pernicious anemia.
This study indicates that the atrophic gastric mucosa in patients with pernicious anemia may retain its potential to regenerate parietal cells – that atrophy is not due to a loss of regenerative potential. Regeneration was seen in patients with the higher titers of parietal cell antibody and did not occur in patients with low titers who also exhibited extensive intestinal metaplasia. It is suggested that persisting high titers of gastric parietal cell antibody in patients with pernicious anemia may be stimulated by the release of antigen from degenerating cells in atrophic gastric glands.
Eleven out of twenty-three patients with thyroid disease and intrinsic-factor (I.F.) antibodies in serum had an atrophic gastritis which did not progress to pernicious anæmia over a period of 3-7 years. In these patients the absorption of vitamin B12 remained normal, and the amount of acid and I.F. in the gastric secretion remained unchanged.Intrinsic-factor Antibodies in Absence of Pernicious Anæmia. 3-7 Year FollowUp.
It is concluded that the patients with I.F. antibody and a non-progressive atrophic gastritis differ from patients with pernicious anæmia in that the I.F. antibody appears in serum at a relatively early phase in the evolution of gastritis when adequate amounts of I.F. are still being produced.
Disorders of intracellular cobalamin metabolism have a variable phenotype and age of onset that are influenced by the severity and location within the pathway of the defect. The prototype and best understood phenotype is cblC; it is also the most common of these disorders.Disorders of Intracellular Cobalamin Metabolism.
The primarily function of cobalt in humans is based on its role in cobalamin (Cbl, vitamin B12). Therefore, this chapter will focus on the physiological roles of Cbl and the importance of cobalt in human health. Cbl acts as the cofactor for two enzymes, i.e., methylmalonyl-CoA mutase and methionine synthase, in humans. Both enzymes are important for health. In addition, unlike other water-soluble vitamins, there is a unique absorption, delivery, and activation system for Cbl in mammals.Cobalt: its role in health and disease.
Studies had shown that about 70% of patients with pernicious anemia will produce detectable levels of such autoantibodies. The clinical symptoms of pernicious anemia developed slowly as B12 stores are sufficient for about 5 years before deficiency lead to the onset of clinical symptoms. Therefore, the full clinical picture of severe intramedullary hemolysis culminating in progressively severe chronic anemia, along with severe neurological symptoms with demyelinisation leading to weakness and paraplegia occurs only rarely. Treatment with parenteral vitamin B12 will lead to a rapid increase of reticulocytes (within 48–72 h) and subsequent correction of anemia.Megaloblastic Anemia.
It is more common in males than in females and has an age peak around 60 year. In pernicious anemia, the gastric mucosa is atrophic and the secretion of intrinsic factor is defective. Inflammatory infiltrate of the gastric submucosa is the earliest gastric lesion in patients with PA. A type A gastritis involving the fundus and sparing the antrum is the typical finding in a patient with autoimmune pernicious anemia. The autoantibodies both to parietal cells and intrinsic factor are detectable both in the serum and gastric secretions. These autoanti- bodies particularly target the H+/K+-ATPase in the parietal cell resulting to gastric atrophy and achlorhydria. Studies had shown that parietal cell autoantibody is detectable in 90% of patients with pernicious anemia and also in 30% of first degree relatives who do not have pernicious anemia, and only about 2–8% of the normal population have low titer of these autoantibodies.
Disorders of malabsorption (food cobalamin malabsorption, intrinsic factor deficiency and abnormal enterocyte cobalamin processing) and transport proteins (transcobalamin II deficiency, R-binder deficiency) mostly lead to disturbed function of the two cobalamin requiring enzymes, methylmalonyl CoA mutase and methionine synthase. Defects of early steps of intracellular cobalamin (cblF, cbl C/D) result in marked deficiencies of both cobalamin co-enzymes and homocystinuria combined with methylmalonic aciduria. Defective synthesis of adenosyl cobalamin in the cbl A/B defects leads to methylmalonyl CoA mutase. Isolated methionine synthase deficiency is also classified as a cobalamin disorder due to its associated deficient formation of methylcobalamin.Genetic defects of folate and cobalamin metabolism.
Breastfed infants of women who have had gastric or intestinal bypass procedures may develop nutritional deficiencies. We describe a 10-month-old exclusively breastfed white male infant who presented with vomiting, failure to thrive, and megaloblastic anemia. He was found to have vitamin B12 deficiency. His mother had undergone a gastric bypass procedure for morbid obesity 2 years prior to her pregnancy with this child. She had subclinical vitamin B12 deficiency, with an abnormal Schilling test that corrected with the addition of intrinsic factor. Therefore, we believe that the mother’s gastric bypass had caused a decrease in available intrinsic factor, resulting in subclinical vitamin B12 deficiency and decreased breast milk B12. Although she was asymptomatic, her breastfed infant developed symptomatic B12 deficiency. This is the first reported case of a maternal gastric bypass resulting in vitamin B12 deficiency in an infant. These mothers should receive vitamin supplements, including vitamin B12, during and after pregnancy, and may require parenterally administered vitamin B12.Nutritional vitamin B12 deficiency in a breastfed infant following maternal gastric bypass.
This entity is probably not as rare as originally thought. It must be considered in the differential diagnosis of low serum cobalamin levels, even among elderly patients, whose conditions often tend to be automatically diagnosed as pernicious anemia.R-Binder Deficiency: A Clinically Benign Cause of Cobalamin Pseudodeficiency.
We conclude that Cbl malabsorption in these children is due to an abnormal IF that is markedly susceptible to acid and proteolytic enzymes which cause a decrease in its molecular weight and Cbl-binding ability and a loss of antigenic determinants that are recognized by the anti-human IF serum.Cobalamin malabsorption in three siblings due to an abnormal intrinsic factor that is markedly susceptible to acid and proteolysis.
Autoimmune diseases are characterized by tissue damage and loss of function due to an immune response that is directed against specific organs. This review is focused on the role of impaired intestinal barrier function on autoimmune pathogenesis.Leaky gut and autoimmune diseases.
This study reports reactions with gastric parietal cells of human and rat origin, of sera from the adult ‘normal’ population of Busselton, Western Australia (3492 sera) and from patients known to have autoimmune gastritis (43 sera). In the normal sera the prevalence of the ‘true’ autoantibody reactive with human gastric parietal cells was 4.8% and there was an age-related increase; the prevalence of heteroantibody reactive with only rat parietal cells was 3.1 %, with no age-related increase. The sera of 43 patients with known pernicious anaemia or atrophic gastritis all reacted with human parietal cells. Two further patients in whom only heteroantibody was demonstrable were shown to have intact gastric function and structure.The parietal cell heteroantibody in human sera: Prevalence in a normal population and relationship to parietal cell autoantibody.
The autoantibodies against gastric parietal cell H+/K+ ATPase had a sensitivity of 68.2% with a specificity of 91.7% for the diagnosis of pernicious anaemia. The respective rates for the autoantibodies against intrinsic factor were 40.9% and 98.6%. The combined sensitivity and specificity rates for both autoantibodies were 86.36% and 90.28%, respectively, the combined positive predictive value was 73.08% and the combined negative predictive value was 95.59%.Pernicious Anaemia–Diagnostic Benefit of the Detection of Autoantibodies Against Intrinsic Factor and Gastric Parietal Cells Antigen H+/K+ ATPase.
The detection of both autoantibodies is helpful in diagnosing pernicious anaemia and the combination of the two assays increases diagnostic sensitivity.
This study provides evidence that testing for gastric parietal cell antibodies is an appropriate screening test for pernicious anaemia, with intrinsic factor antibodies reserved for confirmatory testing or in patients with other autoantibodies that mask the GPC pattern; B12 levels are not related to autoantibody status.Limited Value of Testing for Intrinsic Factor Antibodies With Negative Gastric Parietal Cell Antibodies in Pernicious Anaemia.
Patients with vitamin B12 deficiency are exceedingly sensitive to neurologic deterioration following nitrous oxide anesthesia. If unrecognized, the neurologic deterioration becomes irreversible and may result in death.Neurologic degeneration associated with nitrous oxide anesthesia in patients with vitamin B12 deficiency.
Long-term metformin therapy is significantly associated with lower serum vitamin B12 concentration, yet those at risk are often not monitored for B12 deficiency. Because metformin is first line therapy for type 2 diabetes, clinical decision support should be considered to promote serum B12 monitoring among long-term metformin users for timely identification of the potential need for B12 replacement.Long-term Metformin Therapy and Monitoring for Vitamin B12 Deficiency Among Older Veterans.
A case of the exclusively breast-fed infant of a vegetarian mother is reported. Neurological deterioration commenced between three and six months of age, and progressed to a comatose premoribund state by the age of nine months. Investigations revealed a mild nutritional vitamin B12 deficiency in the mother, and a very severe nutritional B12 deficiency in the infant, with severe megaloblastic anaemia. Treatment of the infant with vitamin B12 resulted in a rapid clinical and haematological improvement, but neurological recovery was incomplete.Brain damage in infancy and dietary vitamin B12 deficiency.
Anti-parietal cell antibody has been reported in nearly all patients with pernicious anaemia in past studies, in contrast with anti-intrinsic factor (IF) antibody which occurs in only 50-70% of such patients. However, observations in the more diverse patient population at our hospital suggest that these prevalences, originally described in predominantly elderly, white patients of European origin, no longer apply. Anti-IF antibody was found in 70% of the 324 patients, with blacks (84%) and Latin Americans (69%) having a significantly higher prevalence than whites (55%). In contrast, only 55% of the 266 patients tested had anti-parietal cell antibody. It was noteworthy that this low rate was similar in all racial groups. However, patients lacking anti-parietal cell antibody were significantly younger than those who had the antibody. Overall, a striking 30% of all patients had anti-IF antibody but not anti-parietal cell antibody, while only 13% had the latter antibody without having anti-IF antibody.Reassessment of the relative prevalences of antibodies to gastric parietal cell and to intrinsic factor in patients with pernicious anaemia: influence of patient age and race.
Taken together, the data indicates an enhanced detection rate by ELISA over immunofluorescence and validates it as a robust diagnostic assay for parietal cell antibody. As parietal cell antibody marks asymptomatic autoimmune gastritis that may progress to end stage gastric atrophy and haematological complications, and as autoimmune gastritis is associated with autoimmune thyroiditic and type 1 diabetes mellitus, early detection of parietal cell antibody by a sensitive ELISA will enable early follow-up of at risk subjects.Parietal Cell Antibody Identified by ELISA Is Superior to Immunofluorescence, Rises With Age and Is Associated With Intrinsic Factor Antibody.
Antibodies of type I, so-called blocking antibodies, were detected in 66% of cases where the diagnosis of pernicious anemia was made. Type II, so-called precipitating antibodies, were found in 47% of patients with antibodies of type I and only in the latter. Certain etiological factors, already noted in the world literature, were found, in particular the link with the female sex and with blood group A. The specificity of these antibodies is very great and false positives are exceptional. We did not find them in any of the 104 controls. They were observed, however, in 5 of the 56 patients where the diagnosis of pernicious anemia was not definite, but it is likely that, in these 5 cases, pernicious anemia existed with some other disease. Our study also showed the limits of other methods of investigation of this disease; hypovitaminimia B12 is often corrected by treatment without proper inductions and B12 malabsorption on the Schilling test may not be corrected by the addition of intrinsic factor.Search for Anti-Intrinsic Factor Antibodies in the Diagnosis of Biermer’s Anemia.
The sensitivity and specificity of the IF Ab test was compared to the Schilling test with regard to making a diagnosis of PA in patients presenting with megaloblastic anaemia and low serum vitamin B12 levels.The Value of the Intrinsic Factor Antibody Test in Diagnosing Pernicious Anaemia.
Relevant statistical analysis showed that in the correct clinical setting, a confident diagnosis of PA could be made without Schilling tests in patients with megaloblastic anaemia, vitamin B12 deficiency and positive IF Ab tests. In a small proportion of patients in whom the IF Ab is negative, Schilling tests still need to be performed.
With the increased concern over rising medical costs and where limited facilities are available, the IF Ab, in the correct clinical setting, is a cost effective and reliable test for diagnosis of PA.
A variety of autoantibodies can be detected in serum samples from patients with pernicious anemia, including antibodies to gastric parietal cells and to intrinsic factor (IF). Antiparietal cell antibodies may have a causative role in the autoimmune gastritis of pernicious anemia and are present in about 85% of affected patients. Antiparietal cell antibodies are nonspecific; they are often present in patients with autoimmune endocrinopathies and are present in 3% to 10% of healthy persons, depending on age.Laboratory Diagnosis of Vitamin B12 and Folate Deficiency.
Compared with the antiparietal cell assay, the anti–IF antibody test is relatively insensitive; only about half of the patients with pernicious anemia have detectable anti-IF antibody. However, anti-IF antibody is highly specific; it is rarely present in healthy patients or in patients with other autoimmune disorders, although it may be detected in some patients with Graves disease. In such cases, a nonprogressive atrophic gastritis (with normal production of IF) has been described.
Vitamin B12 or cobalamin deficiency occurs frequently (> 20%) among elderly people, but it is often unrecognized because the clinical manifestations are subtle; they are also potentially serious, particularly from a neuropsychiatric and hematological perspective. Causes of the deficiency include, most frequently, food-cobalamin malabsorption syndrome (> 60% of all cases), pernicious anemia (15%-20% of all cases), insufficient dietary intake and malabsorption.Vitamin B12 (cobalamin) deficiency in elderly patients.
We would like to thank each and every scientist who takes part in Pernicious Anemia research in any way, shape or form. Your contribution to the the bank of knowledge regarding PA causes, signs, diagnosis and treatment is much appreciated.