Role of (Glu → Arg, Q5R) mutation of the intrinsic factor in pernicious anemia and other causes of low vitamin B12

2008 ◽  
Vol 87 (7) ◽  
pp. 599-600 ◽  
Author(s):  
A. F. Remacha ◽  
E. Del Río ◽  
M. P. Sardà ◽  
C. Canals ◽  
M. Simó ◽  
...  
Keyword(s):  
Vitamin B12 ◽  
Pernicious Anemia ◽  
Intrinsic Factor

Cubilin, the Intrinsic Factor-Vitamin B12 Receptor in Development and Disease

2020 ◽  
Vol 27 (19) ◽  
pp. 3123-3150 ◽  
Author(s):  
Renata Kozyraki ◽  
Olivier Cases
Keyword(s):  
Vitamin B12 ◽  
Cancer Progression ◽  
Intrinsic Factor ◽  
Basic Research ◽  
Toxic Substances ◽  
Human Pathology ◽  
Peripheral Membrane Protein ◽  
Epidermal Growth ◽  
Fgf8 Signaling

Gp280/Intrinsic factor-vitamin B12 receptor/Cubilin (CUBN) is a large endocytic receptor serving multiple functions in vitamin B12 homeostasis, renal reabsorption of protein or toxic substances including albumin, vitamin D-binding protein or cadmium. Cubilin is a peripheral membrane protein consisting of 8 Epidermal Growth Factor (EGF)-like repeats and 27 CUB (defined as Complement C1r/C1s, Uegf, BMP1) domains. This structurally unique protein interacts with at least two molecular partners, Amnionless (AMN) and Lrp2/Megalin. AMN is involved in appropriate plasma membrane transport of Cubilin whereas Lrp2 is essential for efficient internalization of Cubilin and its ligands. Observations gleaned from animal models with Cubn deficiency or human diseases demonstrate the importance of this protein. In this review addressed to basic research and medical scientists, we summarize currently available data on Cubilin and its implication in renal and intestinal biology. We also discuss the role of Cubilin as a modulator of Fgf8 signaling during embryonic development and propose that the Cubilin-Fgf8 interaction may be relevant in human pathology, including in cancer progression, heart or neural tube defects. We finally provide experimental elements suggesting that some aspects of Cubilin physiology might be relevant in drug design.

scholarly journals Chronic Atrophic Gastritis with Negative Intrinsic Factor and Parietal Cell Antibody Presenting as a Severe Hemolytic Anemia

2020 ◽  
Vol 2020 ◽  
pp. 1-4
Author(s):  
G. F. Cittolin-Santos ◽  
S. Khalil ◽  
J. K. Bakos ◽  
K. Baker
Keyword(s):  
Vitamin B12 ◽  
Atrophic Gastritis ◽  
Pernicious Anemia ◽  
Hemolytic Anemia ◽  
Parietal Cell ◽  
Intrinsic Factor ◽  
Peripheral Blood Smear ◽  
Chronic Atrophic Gastritis ◽  
Cell Antibody ◽  
Parietal Cell Antibody

A 28-year-old Caucasian male with Hashimoto’s disease and vitiligo presented with two weeks of dizziness on exertion following pharyngitis which was treated with prednisone 40 mg by mouth once a day for five days. Initial workup revealed anemia, elevated lactate dehydrogenase (LDH), and low haptoglobin. He underwent workup for causes of hemolytic anemia which was remarkable for a peripheral blood smear with hypersegmented neutrophils and low vitamin B12 levels concerning for pernicious anemia. Parietal cell and intrinsic factor antibodies were negative, and he then underwent an esophagogastroduodenoscopy with biopsy. The biopsy was negative for Helicobacter pylori, and the immunohistochemical stains were suggestive of chronic atrophic gastritis. He was started on vitamin B12 1,000 mcg intramuscular injections daily. His hemoglobin, LDH, and haptoglobin normalized. Given the absence of the parietal cell antibody and intrinsic factor antibody, this is a rare case of seronegative pernicious anemia.

scholarly journals Absorption of Liver-bound Vitamin B12 in Relation to Intrinsic Factor

Blood ◽  
1968 ◽  
Vol 32 (2) ◽  
pp. 313-323 ◽  
Author(s):  
KUNIO OKUDA ◽  
ISAO TAKARA ◽  
TERUMI FUJII
Keyword(s):  
Vitamin B12 ◽  
Pernicious Anemia ◽  
Rat Liver ◽  
Intrinsic Factor ◽  
In Vitro Digestion ◽  
Enhanced Absorption ◽  
Biochemical Studies ◽  
Peptide Complexes ◽  
Liver Powder

Abstract Rat liver containing radioactive native B12 was prepared by repeated injections of 57Co-OH-B12, and absorption of liver B12 was measured in patients with pernicious anemia and in subjects without stomach, using physiologic doses. It was found that absorption of liver B12 was very poor, not superior to that of free OH-B12, and coadministration of IFC markedly enhanced absorption. In vitro digestion of rat liver with several enzymes, as determined from liberation of dialyzable radioactivity, suggested its easy digestibility. Biochemical studies of the dialyzable products of liver containing 57Co-B12 failed to demonstrate any detectable quantities of radioactivity other than free 57Co-OH-B12. A study in which cow liver powder mixed with a small quantity of 57Co-CN-B12 was fed to humans and digestion of liver was estimated from the reduction in absorption of radioactivity, indicated that most of the extractable liver B12 was liberated free in the intestine. Thus, no evidence has been obtained for the production of B12-peptide complexes from liver by digestion that require no IF for absorption.

scholarly journals Vitamin B12 Malabsorption Due to Intrinsic Factor Deficiency in Indian Subjects

Blood ◽  
1972 ◽  
Vol 40 (5) ◽  
pp. 747-753 ◽  
Author(s):  
H. G. Desai ◽  
F. P. Antia
Keyword(s):  
Vitamin B12 ◽  
Pernicious Anemia ◽  
Indian Population ◽  
Intrinsic Factor ◽  
Subacute Combined Degeneration ◽  
Factor Deficiency ◽  
Vitamin B12 Absorption ◽  
Intrinsic Factor Deficiency ◽  
Intrinsic Factor Antibody ◽  
Vitamin B12 Malabsorption

Abstract Sixteen patients (from Bombay) with severe vitamin B12 malabsorption due to intrinsic factor deficiency, presenting as subacute combined degeneration of the cord (7), tropical sprue (3), anemia (2), thyrotoxicosis (2), diabetes mellitus (1), and pain in the abdomen (1), are reported. The difficulties of establishing a definite diagnosis of pernicious anemia in Indian population are described. The lower incidence of circulating intrinsic factor antibody (IFA) in Indian patients with histamine-fast achlorhydria and poor vitamin B12 absorption is emphasized. The necessity of separating atrophic gastritis, with severely impaired vitamm B12 absorption, from pernicious anemia on the basis of absence or presence of IFA in serum and/or gastric juice cannot be overemphasized.

Effect of Rat Intrinsic Factor on Vitamin B12 Absorption in Pernicious Anemia

Science ◽  
1957 ◽  
Vol 126 (3273) ◽  
pp. 558-558 ◽  
Author(s):  
J. ABELS ◽  
M. G. WOLDRING ◽  
J. J. M. VEGTER ◽  
H. O. NIEWEG
Keyword(s):  
Vitamin B12 ◽  
Pernicious Anemia ◽  
Intrinsic Factor ◽  
Vitamin B12 Absorption

scholarly journals Total Body Counting in the Assessment of Vitamin B12 Absorption in Patients with Pernicious Anemia, Achlorhydria Without Pernicious Anemia and in Acid Secretors

Blood ◽  
1970 ◽  
Vol 36 (1) ◽  
pp. 20-27 ◽  
Author(s):  
W. J. IRVINE ◽  
D. R. CULLEN ◽  
LAURA SCARTH ◽  
J. D. SIMPSON ◽  
S. H. DAVIES
Keyword(s):  
Vitamin B12 ◽  
Pernicious Anemia ◽  
Intrinsic Factor ◽  
Body Counting ◽  
Acid Secreting ◽  
Vitamin B12 Absorption ◽  
Upper Level ◽  
Equivocal Result ◽  
Total Body ◽  
Cent Error

Abstract The absorption of 58Co-vitamin B12 was assessed by the method of total body counting in 25 patients with frank P.A., five with latent P.A., 47 with achlorhydria but without malabsorption of vitamin B12 and 47 acid-secreting patients. A total of 192 tests was done. With or without prior stimulation of intrinsic factor secretion by pentagastrin the upper level of absorption of vitamin B12 in patients with frank or latent P.A. was 25 per cent. Taking an equivocal result to be 21-25 per cent inclusive, the total body counting method was able to distinguish P.A. patients from those with achlorhydria without P.A. with 87 per cent accuracy and one per cent error and from non-P.A. achlorhydric patients and acid secretors combined with 91 per cent accuracy and 0.5 per cent error. Pentagastrin stimulation did not improve the separation between achlorhydric patients with and without P.A. but raised the lower limit of retention of vitamin B12 from 24 to 44 per cent in the acid secreting patients. The method of total body counting is recommended as a method of assessing vitamin B12 absorption.

scholarly journals The Effect of Various Metabolites on the Growth of Marrow Cells in Vitro

Blood ◽  
1955 ◽  
Vol 10 (7) ◽  
pp. 735-752 ◽  
Author(s):  
HAROLD T. SWAN ◽  
EDWARD H. REISNER ◽  
MORRIS SILVERMAN
Keyword(s):  
Vitamin B12 ◽  
Pernicious Anemia ◽  
Folinic Acid ◽  
Intrinsic Factor ◽  
Suspension Cultures ◽  
Normal Serum ◽  
Red Cell ◽  
Inhibitory Effects ◽  
Glass Surfaces

Abstract Marrow was cultured on chick plasma clots, glass surfaces and in suspension and the influence of various metabolites and antimetabolites on the growth and differentiation of red cell precursors was studied. Vitamin B12 appeared to stimulate cell growth in cultures grown on clots and to convert megaloblastic hematopoiesis to normoblastic in cultures grown on glass. In suspension cultures of megaloblastic marrows in pernicious anemia serum significant cell increases were obtained with the addition of folinic acid, but not with vitamin B12. Both vitamin B12 and folinic acid appeared to accelerate the conversion of megaloblasts to normoblasts in differential counts of stained smears of such cultures. No enhancing effect of intrinsic factor upon the activity of B12 in suspension cultures of megaloblasts was observed. The effect of folinic acid could be blocked by colchicine and folinic acid could reverse the inhibitory effects of Amethopterin. These facts indicated that folinic acid acted in suspension cultures by stimulating mitosis. Megaloblasts could be produced from normoblastic marrows by culturing them in pernicious anemia serum, or in normal serum in the presence of Amethopterin.

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