High serum cobalamin levels in the clinical setting - clinical associations and holo-transcobalamin changes

Abstract

Whereas low cobalamin levels have been studied intensively, systematic information about high levels, especially in the clinical setting, is scarce. Therefore, a prospective comparison was done of 60 patients with high cobalamin levels and 75 with normal levels obtained by a hospital laboratory over a 2.5 month period. Associations with clinical disorders and laboratory test results were examined. Transcobalamin (TC) I and II were measured, especially the holoproteins (TC carrying circulating endogenous cobalamin) which were fractionated with microfine silica powder. High cobalamin levels (> 664 pmol/l; > 900 ng/l) occurred in 94 of 670 consecutive clinically requested assays (14%). The only independently significant associations with a high cobalamin level were renal failure among the clinical disorders (P=0.01), elevated serum creatinine (P=0.0001) and diminished albumin (P=0.0002) levels among laboratory tests. Both holo-TC I and holo-TC II levels were increased in renal failure (P=0.0001) but the increase was relatively greater in holo-TC II. The results indicate that high cobalamin levels are more frequent than low ones in clinical practice and appear to be associated often with renal failure. The elevation of both holo-TC II and holo-TC I suggests that several mechanisms are operative. The accumulation of holo-TC II suggests that cellular uptake of cobalamin by the abundant TC II receptors in the kidney may be impaired. The much better known association of high cobalamin levels with leucocytic disorders is rare, and no association was seen with liver disease.

Measurement of Total Vitamin B12 and Holotranscobalamin, Singly and in Combination, in Screening for Metabolic Vitamin B12 Deficiency

“…Unlike total vitamin B 12 , the holoTC assay has not been automated. In addition, the determinants of holoTC need to be systematically investigated: plasma holoTC increases in renal disease (15,19 ), and from this observation, Herrmann et al (15 ) concluded that holoTC cannot be used as an indicator of vitamin B 12 status in patients with renal disease. HoloTC may also increase after vitamin B 12 intake (20 ), and we (21 ) and others (22)(23)(24)(25)(26)(27)(28)(29)(30) have observed that the plasma holoTC concentration is affected by a common polymorphism in TC (C776G), which can also influence methylmalonic acid and homocysteine concentrations.…”

Markedly Increased Vitamin B12 Concentrations Attributable to IgG–IgM–Vitamin B12 Immune Complexes

“…myeloproliferative disorders, and hypereosinophilic syndrome, none of these were present in our patient (3)(4)(5)(6)(7)(8)(9)(10)(11). These clinical conditions are characterized by high myeloid cell mass and turnover associated with maturation (21,22 ). The reason for increased serum vitamin B 12 in the above-mentioned conditions is the increased synthesis and release of HC from the secondary granules of myeloid cells (21,22 ).…”

“…These clinical conditions are characterized by high myeloid cell mass and turnover associated with maturation (21,22 ). The reason for increased serum vitamin B 12 in the above-mentioned conditions is the increased synthesis and release of HC from the secondary granules of myeloid cells (21,22 ). A correlation between serum unsaturated vitamin B 12 binding capacity and total granulocyte pool has been reported (23 ).…”

Metformin and Vitamin B12 Deficiency: Where Do We Stand?

“…Renal failure is associated with elevated levels of holo-TC-II (67). Mild renal insufficiency has a modest impact on serum vitamin B12 and holo-TC-II levels, unlike its effect on MMA and homocyteine concentrations (59).…”