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.
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.
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 B12metabolism: eight complementation groups – eight genes.
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.
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.
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.
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.
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.