scholarly journals Gel Filtration Studies of Serum B12 Binding: An Abnormal Pattern in Patients with Vitamin B12 Deficiency

Blood ◽  
1969 ◽  
Vol 34 (6) ◽  
pp. 774-781 ◽  
Author(s):  
CHRISTINE LAWRENCE
Keyword(s):  
Molecular Weight ◽  
Vitamin B12 ◽  
Binding Capacity ◽  
Gel Filtration ◽  
Vitamin B12 Deficiency ◽  
Normal Serum ◽  
B12 Deficiency ◽  
Abnormal Pattern ◽  
Normal Controls

Abstract 57CoB12 was added to serum in vitro to study its binding by the three known serum B12-binders in patients with vitamin B12 deficiency and in normal controls. Gel filtration through columns of Sephadex G-200 was used to separate the low (beta) and high (alpha1 and beta) molecular weight B12-binding fractions. Electrophoresis on filter paper was used to separate the alpha1- and beta-globulins. The alpha1-globulin fraction in the serum of B12-deficient patients bound more of the added 57CoB12 than did this fraction in normal serum, presumably because this binder of the serum endogenous vitamin B12 is much less saturated in B12-deficiency. However, the total B12 binding capacity of the alpha1-globulin (for endogenous plus added vitamin B12) was lower in B12-deficient than in normal serum. The low molecular weight beta-binder bound more added 57CoB12 in B12-deficient than in normal serum, whereas the high molecular weight beta binder had a much lower B12-binding capacity in deficient than in normal serum. These abnormalities were independent of the cause of the vitamin B12 deficiency and disappeared after successful treatment with vitamin B12.

scholarly journals Circulating antibody to transcobalamin II causing retention of vitamin B12 in the blood

Blood ◽  
1977 ◽  
Vol 49 (6) ◽  
pp. 987-1000 ◽  
Author(s):  
R Carmel ◽  
B Tatsis ◽  
L Baril
Keyword(s):  
Vitamin B12 ◽  
Binding Capacity ◽  
Megaloblastic Anemia ◽  
Serum Vitamin ◽  
Vitamin B12 Deficiency ◽  
High Serum ◽  
The Status ◽  
B12 Deficiency ◽  
Long Acting

A patient with recurrent pulmonary abscess, weight loss, and alcoholism was found to have extremely high serum vitamin B12 and unsaturated vitamin B12-binding capacity (UBBC) levels. While transcobalamin (TC) II was also increased, most of his UBBC was due to an abnormal binding protein which carried greater than 80% of the endogenous vitamin B12 and was not found in his saliva, granulocytes, or urine. This protein was shown to be a complex of TC II and a circulating immunoglobulin (IgGkappa and IgGlambda). Each IgG molecule appeared to bind two TC II molecules. The reacting site did not interfere with the ability of TC II to bind vitamin B12, but did interfere with its ability to transfer the vitamin to cells in vitro. The site was not identical to that reacting with anti-human TC II antibody produced in rabbits. Because of this abnormal complex, 57Co-vitamin B12 injected intravenously was cleared slowly by the patient. However, no metabolic evidence for vitamin B12 deficiency was demonstrable, although the patient initially had megaloblastic anemia apparently due to folate deficiency. The course of the vitamin B12-binding abnormalities was followed over 4 yr and appeared to fluctuate with the status of the patient's illness. The IgG-TC II complex resembled one induced in some patients with pernicious anemia by intensive treatment with long-acting vitamin B12 preparations. The mechanism of induction of the antibody formation in our patient is unknown.

scholarly journals Circulating antibody to transcobalamin II causing retention of vitamin B12 in the blood

Blood ◽  
1977 ◽  
Vol 49 (6) ◽  
pp. 987-1000 ◽  
Author(s):  
R Carmel ◽  
B Tatsis ◽  
L Baril
Keyword(s):  
Vitamin B12 ◽  
Binding Capacity ◽  
Megaloblastic Anemia ◽  
Serum Vitamin ◽  
Vitamin B12 Deficiency ◽  
High Serum ◽  
The Status ◽  
B12 Deficiency ◽  
Long Acting

Abstract A patient with recurrent pulmonary abscess, weight loss, and alcoholism was found to have extremely high serum vitamin B12 and unsaturated vitamin B12-binding capacity (UBBC) levels. While transcobalamin (TC) II was also increased, most of his UBBC was due to an abnormal binding protein which carried greater than 80% of the endogenous vitamin B12 and was not found in his saliva, granulocytes, or urine. This protein was shown to be a complex of TC II and a circulating immunoglobulin (IgGkappa and IgGlambda). Each IgG molecule appeared to bind two TC II molecules. The reacting site did not interfere with the ability of TC II to bind vitamin B12, but did interfere with its ability to transfer the vitamin to cells in vitro. The site was not identical to that reacting with anti-human TC II antibody produced in rabbits. Because of this abnormal complex, 57Co-vitamin B12 injected intravenously was cleared slowly by the patient. However, no metabolic evidence for vitamin B12 deficiency was demonstrable, although the patient initially had megaloblastic anemia apparently due to folate deficiency. The course of the vitamin B12-binding abnormalities was followed over 4 yr and appeared to fluctuate with the status of the patient's illness. The IgG-TC II complex resembled one induced in some patients with pernicious anemia by intensive treatment with long-acting vitamin B12 preparations. The mechanism of induction of the antibody formation in our patient is unknown.

scholarly journals A new case of deficiency of the R binder for cobalamin, with observations on minor cobalamin-binding proteins in serum and saliva

Blood ◽  
1982 ◽  
Vol 59 (1) ◽  
pp. 152-156
Author(s):  
R Carmel
Keyword(s):  
Molecular Weight ◽  
Alcohol Abuse ◽  
Incidental Findings ◽  
Clinical Presentation ◽  
Binding Capacity ◽  
Normal Serum ◽  
Serum Component ◽  
Almost All ◽  
Normal Controls ◽  
Low Serum

A patient presented at the age of 77 yr with a low serum cobalamin level. Subsequent study showed that he had persistently very low R binder (TC I) cobalamin-binding capacity in serum (less than 5 ng/liter versus 213 +/- 171 ng/liter in normal controls), and that almost all of his endogenous serum cobalamin was carried by TC II instead of TC I. His saliva also demonstrated virtually undetectable R binder (binding capacity of 31–38 ng/liter versus 41,690 +/- 23,820 ng/liter for control subjects). Unlike previous cases of R binder deficiency, he seemed to maintain normal serum cobalamin levels while receiving monthly cyanocobalamin injections. This and his normal serum unsaturated binding capacity were due to elevated TC II levels. TC II carried 72%-98% of his endogenous cobalamin, the rest being attached to minor binders. As incidental findings, the patient had a serum component of molecular weight of approximately 70,000 that carried 7%- 8% of his endogenous cobalamin and also had small quantities of TC II demonstrable in his saliva. Both these heretofore unappreciated minor peaks were identifiable because of the lack of R binder. The patient's clinical presentation supports the conclusion that R binder deficiency is a benign disorder. Whether his mild hypersegmentation of neutrophils and neuropathy were related to the R binder deficiency or, more likely, arose from coexisting folate deficiency and alcohol abuse, the overall picture contrasts dramatically with the severe clinical sequelae of TC II deficiency.

scholarly journals Holotranscobalamin Is a Useful Marker of Vitamin B12 Deficiency in Alcoholics

2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Alberto Fragasso ◽  
Clara Mannarella ◽  
Angela Ciancio ◽  
Oronzo Scarciolla ◽  
Nicoletta Nuzzolese ◽  
...  
Keyword(s):  
Vitamin B12 ◽  
Vitamin B12 Deficiency ◽  
Serum Levels ◽  
Normal Serum ◽  
Serum Folate ◽  
Gamma Glutamyl Transpeptidase ◽  
B12 Deficiency ◽  
Male Patients ◽  
Positive Correlations ◽  
Glutamyl Transpeptidase

Background. Measurement of serum cobalamin (Cbl) levels is the standard investigation for assessing vitamin B12 deficiency. Falsely increased values of Cbl can be caused by alcoholic liver disease. Measurement of total vitamin B12 serum levels might be misleading in alcoholics, because a tissue metabolic deficiency is possible even with normal serum Cbl levels. Holotranscobalamin (HoloTC), the Cbl metabolically active fraction, is considered as a better index of vitamin B12 deficiency.Methods. For assessing vitamin B12 status, we evaluated 22 adult alcoholic male patients by measuring in parallel serum Cbl, serum folate and red blood cell folate levels, HoloTC levels by the AxSYM assay.Results. HoloTC values were reduced in 3 alcoholics with borderline-low Cbl values. Significant positive correlations were found between serum Cbl and HoloTC levels, serum Cbl and gamma-glutamyl transpeptidase (GGT).Conclusion. HoloTC measurement is a useful option for assessing vitamin B12 status in alcoholics, particularly in the subjects with borderline Cbl values and may be considered an early marker of vitamin B12 deficiency.

scholarly journals Folic acid metabolism in vitamin B12-deficient sheep. Effects of injected methionine on liver constituents associated with folate metabolism

1974 ◽  
Vol 142 (1) ◽  
pp. 119-126 ◽  
Author(s):  
Jeffrey M. Gawthorne ◽  
Richard M. Smith
Keyword(s):  
Vitamin B12 ◽  
Methylenetetrahydrofolate Reductase ◽  
Vitamin B12 Deficiency ◽  
Folate Metabolism ◽  
British Library ◽  
Synthetase Activity ◽  
Intravenous Injections ◽  
B12 Deficiency ◽  
Lending Library

1. A study was made of the effects of injected l-methionine on the activity of several enzymes of folate metabolism, and on the transport of methotrexate in liver preparations from vitamin B12-deficient ewes and their pair-fed controls receiving vitamin B12. 2. The activities of dihydrofolate reductase (EC 1.5.1.3) and 5-methyltetrahydrofolate–homocysteine transmethylase were significantly decreased in the liver of vitamin B12-deficient animals, but were unaffected by l-methionine. 3. The concentration of S-adenosyl-l-methionine in the liver of deficient animals was about one-half of that in normal animals, and was restored to normal by either vitamin B12 or l-methionine. 4. Methylenetetrahydrofolate reductase (EC 1.1.1.68) from sheep liver was inhibited by S-adenosyl-l-methionine in vitro, but not by concentrations of S-adenosyl-l-methionine found in the liver of vitamin B12-deficient animals after injection of physiological amounts of l-methionine. 5. Pteroylpolyglutamate synthetase activity was significantly increased in the liver of vitamin B12-deficient animals, and was decreased by intravenous injections of l-methionine. 6. l-Methionine injections increased the initial rate of uptake of methotrexate in liver slices from deficient animals and acted synergistically with vitamin B12 to increase the quantity taken up in 40min. The failure of folate metabolism in vitamin B12 deficiency can be satisfactorily explained if l-methionine similarly affects the membrane transport of naturally occurring folates. 7. Further details of the results have been deposited as Supplementary Publication SUP 50028 (4 pages) at the British Library (Lending Division), (formerly the National Lending Library for Science and Technology), Boston Spa, Yorks. LS23 7BQ, U.K., from whom copies may be obtained on the terms given in Biochem. J. (1973) 131, 5.

Serum Folate of Less than 7.0 ng/mL is a Marker of Malnutrition

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S87-S87
Author(s):  
S N Mattox ◽  
D Kozman ◽  
G Singh
Keyword(s):  
Vitamin B12 ◽  
Clinical Laboratory ◽  
Tertiary Care ◽  
Vitamin B12 Deficiency ◽  
Folate Deficiency ◽  
Normal Serum ◽  
Serum Folate ◽  
Folate Supplementation ◽  
B12 Deficiency ◽  
The Difference

Abstract Introduction/Objective To identify clinical/laboratory factors associated with folate deficiency in tertiary care patients. Methods We reviewed the medical records of 1019 patients with serum folate <7.0 ng/mL, 301 patients with serum folate of 15 ng/mL, and 300 patients with serum folate > 23 ng/mL. Results Serum prealbumin levels were subnormal in 54.8% of patients with serum folate <7.0 ng/mL. Vitamin B12, hemoglobin, and serum albumin levels were significantly lower in the <7.0 ng/mL folate group. In 62.4% of patients with serum folate <7.0 ng/mL, 1 or more markers of malnutrition were present. The low-folate group had a significantly higher prevalence of gastrointestinal (GI) disorders, sepsis, and abnormal serum creatinine level. There were no significant differences in the 2 groups regarding diabetes; behavioral/neurological disorders, including drug and alcohol abuse; bariatric surgery; or a diagnosis of malnutrition. The average body mass index (BMI) for the <7.0 ng/mL and 15 ng/mL folate groups was significantly different (28.89 and 28.31, respectively), although the difference does not appear to be clinically meaningful. Conclusion The prevalence of folate deficiency depends on what is considered a normal serum folate level. Approximately 10% of tertiary care patients have levels <7.0 ng/mL and exhibit other markers of malnutrition. It is recommended that patients with GI disorders, chronic kidney disease, and sepsis be routinely tested for serum folate levels, before administration of vitamin supplements. Patients with serum folate levels <7.0 ng/mL should be evaluated for malnutrition, despite BMI > 25. Folate supplementation should be administered only after excluding coexisting vitamin B12 deficiency.

scholarly journals The Plasma Clearance and Urinary Excretion of Parenterally Administered 58Co B12

Blood ◽  
1956 ◽  
Vol 11 (1) ◽  
pp. 31-43 ◽  
Author(s):  
D. L. MOLLIN ◽  
W. R. PITNEY ◽  
S. J. BAKER ◽  
J. E. BRADLEY
Keyword(s):  
Urinary Excretion ◽  
Vitamin B12 ◽  
Plasma Clearance ◽  
Vitamin B12 Deficiency ◽  
Normal Subjects ◽  
Normal Serum ◽  
Chronic Myelocytic Leukemia ◽  
Intravenous Injections ◽  
Myelocytic Leukemia ◽  
B12 Deficiency

Abstract Intravenous injections of 1.5 µg. of 58Co B12 were given to subjects with normal serum B12 concentrations, to patients with vitamin B12 deficiency and to patients with chronic myelocytic leukemia. The rate of plasma clearance of radioactivity after this dose was slowest in patients with chronic myelocytic leukemia and patients with pernicious anemia in severe relapse. In patients with vitamin B12 deficiency, serum B12 concentrations were estimated microbiologically at frequent intervals after the injection. There was a good correlation between the results obtained by microbiological assay and as calculated from plasma radioactivity. Significant differences were not observed between the urinary excretion of radioactivity by normal subjects and patients with B12 deficiency.

scholarly journals A new case of deficiency of the R binder for cobalamin, with observations on minor cobalamin-binding proteins in serum and saliva

Blood ◽  
1982 ◽  
Vol 59 (1) ◽  
pp. 152-156 ◽  
Author(s):  
R Carmel
Keyword(s):  
Molecular Weight ◽  
Alcohol Abuse ◽  
Incidental Findings ◽  
Clinical Presentation ◽  
Binding Capacity ◽  
Normal Serum ◽  
Serum Component ◽  
Almost All ◽  
Normal Controls ◽  
Low Serum

Abstract A patient presented at the age of 77 yr with a low serum cobalamin level. Subsequent study showed that he had persistently very low R binder (TC I) cobalamin-binding capacity in serum (less than 5 ng/liter versus 213 +/- 171 ng/liter in normal controls), and that almost all of his endogenous serum cobalamin was carried by TC II instead of TC I. His saliva also demonstrated virtually undetectable R binder (binding capacity of 31–38 ng/liter versus 41,690 +/- 23,820 ng/liter for control subjects). Unlike previous cases of R binder deficiency, he seemed to maintain normal serum cobalamin levels while receiving monthly cyanocobalamin injections. This and his normal serum unsaturated binding capacity were due to elevated TC II levels. TC II carried 72%-98% of his endogenous cobalamin, the rest being attached to minor binders. As incidental findings, the patient had a serum component of molecular weight of approximately 70,000 that carried 7%- 8% of his endogenous cobalamin and also had small quantities of TC II demonstrable in his saliva. Both these heretofore unappreciated minor peaks were identifiable because of the lack of R binder. The patient's clinical presentation supports the conclusion that R binder deficiency is a benign disorder. Whether his mild hypersegmentation of neutrophils and neuropathy were related to the R binder deficiency or, more likely, arose from coexisting folate deficiency and alcohol abuse, the overall picture contrasts dramatically with the severe clinical sequelae of TC II deficiency.

scholarly journals Transcobalamin deficiency: vitamin B12 deficiency with normal serum B12 levels

2019 ◽  
Vol 12 (10) ◽  
pp. e232319 ◽  
Author(s):  
Sanjeev Khera ◽  
Suman Kumar Pramanik ◽  
Saroj Kumar Patnaik
Keyword(s):  
Vitamin B12 ◽  
Inborn Error ◽  
Autosomal Recessive ◽  
Vitamin B12 Deficiency ◽  
Genetic Evaluation ◽  
Normal Serum ◽  
Definitive Diagnosis ◽  
Early Infancy ◽  
Vitamin B ◽  
B12 Deficiency

Transcobalamin (TC) deficiency is a rare autosomal recessive inborn error of cobalamin transport which clinically manifests in early infancy. We describe a child with TC deficiency who presented with classical clinical and lab stigmata of inborn error of vitamin B12 metabolism except normal serum B12 levels. He was started on empirical parenteral cobalamin supplements at 2 months of age; however, the definitive diagnosis could only be established at 6 years of age when a genetic evaluation revealed homozygous nonsense variation in exon 8 of the TCN2 gene (chr22:g.31019043C>T).

Sign in / Sign up

Export Citation Format

Share Document