Low Serum Cobalamin Levels Research Articles

Physician response to low serum cobalamin levels

Physician response to low serum cobalamin levels

The distribution of endogenous cobalamin among cobalamin-binding proteins in the blood in normal and abnormal states

Our information about cobalamin transport in the blood is largely based on studies of unsaturated cobalamin-binding proteins. Therefore, the distribution of endogenous cobalamin among these proteins was examined. Normally, R binder (transcobalamin I) carries most of the cobalamin circulating at any given moment, but the proportion varies greatly. Transcobalamin II carries a larger fraction of the cobalamin present in portal vein blood than in hepatic and axillary vein blood. In disease, transcobalamin II occasionally holds the bulk of the vitamin present in peripheral blood. Such was observed in three patients showing quantitative changes of unsaturated binder (either diminished R binder or increased transcobalamin II), but in two cases of chronic liver disease this was independent of unsaturated transcobalamin levels. Four patients with low serum cobalamin levels maintained normal distribution, indicating proportional cobalamin depletion from both binder pools. Small amounts of vitamin were attached in many sera to minor binders, and occasionally seemed to circulate free. These results demonstrate that assumptions that cobalamin is always attached largely to transcobalamin I are not warranted. Cobalamin distribution appears to be governed by many factors, of which the amounts of the binding proteins is only one.

Hereditary Transcobalamin II Deficiency with Subnormal Serum Cobalamin Levels

An infant with transcobalamin II deficiency had the unusual feature of a low serum cobalamin level. Moreover, the level did not rise greatly with cobalamin therapy. Clinically, the features of the infant's illness were unexceptional other than the somewhat delayed onset of symptoms at 3 1/2 months of age. In addition, the patient's impaired antibody response to specific antigen challenge was not completely corrected following cobalamin therapy, and this result contrasts with the findings in the only previous examination of this feature of the disorder. As in previous cases, the transcobalamin II deficiency was accompanied by findings in the serum of complexing of the patient's R binder and the relative prominence of a cobalamin-binding peak eluting at a molecular weight of approximately 70,000 on Sephadex G-200 gel chromatography. In addition, the total serum R binder (free and complexed) level was low. This case demonstrates that transcobalamin II deficiency should be considered in any infant with a low serum cobalamin level in the first few months of life.

Congenital Transcobalamin II Deficiency Presenting Atypically With a Low Serum Cobalamin Level: Studies Demonstrating the Coexistence of a Circulating Transcobalamin I (R Binder) Complex

A case of transcobalamin II deficiency with several unique features is described. The clinical presentation was typical, except for a slightly delayed age at presentation and the occurrence of apparent neurologic dysfunction from the beginning. The unusual biochemical feature was a low serum cobalamin level (97 pg/ml). Several cobalamin-binding protein abnormalities coexisted and antedated cobalamin therapy. Chief among these was the complexing of all serum R binder (transcobalamin I), leaving the patient with no detectable R binder. This defect appeared to be transient. Noteworthy, too, was a prominent binder of 70,000 mol wt that also carried the bulk of his serum cobalamin after therapy; it was prominent in his presumably heterozygous relatives too. The interrelationship between all these abnormalities is intriguing but unclear. The abnormality in transcobalamin II deficiency is clearly not limited solely to deficiency of transcobalamin II. It is also evident that this entity must now be considered in the differential diagnosis of low serum cobalamin levels in infancy.

Congenital transcobalamin II deficiency presenting atypically with a low serum cobalamin level: studies demonstrating the coexistence of a circulating transcobalamin I (R binder) complex

A case of transcobalamin II deficiency with several unique features is described. The clinical presentation was typical, except for a slightly delayed age at presentation and the occurrence of apparent neurologic dysfunction from the beginning. The unusual biochemical feature was a low serum cobalamin level (97 pg/ml). Several cobalamin-binding protein abnormalities coexisted and antedated cobalamin therapy. Chief among these was the complexing of all serum R binder (transcobalamin I), leaving the patient with no detectable R binder. This defect appeared to be transient. Noteworthy, too, was a prominent binder of 70,000 mol wt that also carried the bulk of his serum cobalamin after therapy; it was prominent in his presumably heterozygous relatives too. The interrelationship between all these abnormalities is intriguing but unclear. The abnormality in transcobalamin II deficiency is clearly not limited solely to deficiency of transcobalamin II. It is also evident that this entity must now be considered in the differential diagnosis of low serum cobalamin levels in infancy.

R-Binder Deficiency

A patient with R-binder deficiency lacked this cobalamin-binding protein in serum, saliva, gastric juice, and leukocytes, as demonstrated by cobalamin-binding ability and radioimmunoassay. The patient's condition was first detected because of a low serum cobalamin (vitamin B₁₂) level. His level of serum cobalamin, however, which was carried largely by transcobalamin II, was not as decreased as in the initial cases reported and was higher by some assays than by others. The demonstration of normal bone marrow morphological appearance and deoxyuridine suppression test findings, lack of attributable neurological dysfunction, and absence of methylmalonic aciduria make clear that deficiency of R binder, whose function is unknown, did not produce notable disturbance of cobalamin metabolism. 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. (<i>JAMA</i>1983;250:1886-1890)

A New Case of Deficiency of the R Binder for Cobalamin, With Observations on Minor Cobalamin-Binding Proteins in Serum and Saliva

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.

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

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.