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Influence of cobalamin deficiency compared with that of cobalamin absorption on serum holo-transcobalamin II^1,2,3

¹ From the Department of Medicine, New York Methodist Hospital, Brooklyn (XC and RC); the Hematology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain (AFR and MPS); and the Department of Medicine, Weill Medical College of Cornell University, New York (RC).

Background: Cobalamin attached to transcobalamin II (TC II), known as holo-TC II, is the active cobalamin fraction taken up by tissues. Holo-TC II is also the form in which absorbed cobalamin enters the circulation from the ileum. Therefore, holo-TC II has been proposed variously as a marker of cobalamin adequacy, cobalamin absorption, or both, including even its advocacy as a surrogate Schilling test. Such claims carry conflicting diagnostic implications because metabolic adequacy and absorption are not identical.

Objective: The objective was to examine metabolic and absorptive influences on holo-TC II.

Design: Treated patients with pernicious anemia (PA), who have abnormal absorption but a normal metabolic status, were chosen as the model to differentiate between the effects of the 2 cobalamin-related characteristics. Serum holo-TC II and indexes of cobalamin metabolism in 23 treated patients were compared with those of 6 untreated PA patients (abnormal absorption and metabolic status) and 33 control subjects (normal absorption and metabolic status).

Results: Holo-TC II, which correlated directly with cobalamin and inversely with homocysteine, was significantly higher in treated PA patients in metabolic remission than in untreated PA patients (74 ± 59 compared with 9 ± 6 pmol/L) and was significantly lower than in control subjects (105 ± 58 pmol/L), although the latter difference was small and the values overlapped greatly.

Conclusions: Metabolic cobalamin status is a major determinant of serum holo-TC II. Absorption status may have mild influence as well, although other explanations remain possible. Serum holo-TC II cannot be used clinically to diagnose cobalamin malabsorption because of overlap with normal values. The influences on holo-TC II are complex and require careful analysis.

Key Words: Holo-transcobalamin II • cobalamin • cobalamin absorption • cobalamin deficiency • homocysteine