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Licensed Unlicensed Requires Authentication Published by De Gruyter November 23, 2012

Three family members with elevated plasma cobalamin, transcobalamin and soluble transcobalamin receptor (sCD320)

  • Elke Hoffmann-Lücke EMAIL logo , Johan F.B. Arendt , Peter H. Nissen , Gustav Mikkelsen , Jan O. Aasly and Ebba Nexo


Background: Plasma cobalamin is requested in order to diagnose cobalamin deficiency and low levels confirm a deficient state. Here, we present three family members with unexpected high levels of cobalamin.

Methods: We included a patient referred for cobalamin measurement due to neurological symptoms, her son and her daughter. Mother and son both suffered from myotonic dystrophy type II, while the daughter tested negative for this disease. Blood samples were analyzed for cobalamin, haptocorrin, transcobalamin, holoTC, and sCD320. We employed gel filtration and antibody precipitation for further characterization. The protein coding region of the TCN2 gene, encoding transcobalamin, was sequenced.

Results: The patient, her {son} and [daughter] all had cobalamin levels above the measurement range of the routine method employed (>1476 pmol/L). Total transcobalamin and (holoTC) were 5980 (1500), {5260 (2410)} and [5630 (1340)] pmol/L, which is well above the upper reference limits of 1500 (160) pmol/L. The sCD320 concentration was also well above the upper reference limit of 97 arb.u.: 1340, {1510} and [1090] arb.u. Haptocorrin levels were within the reference range and no signs of cobalamin deficiency were found. DNA sequencing of the TCN2 gene revealed several known polymorphisms not associated with highly elevated transcobalamin levels. Upon gel filtration, sCD320 eluted as a larger molecule than previously reported. By incubation with anti-transcobalamin antibodies, we precipitated both transcobalamin and part of sCD320.

Conclusions: The high cobalamin levels were mainly explained by high levels of holoTC, possibly caused by complex formation with its soluble receptor, sCD320. The family occurrence points to a genetic explanation.

Corresponding author: Elke Hoffmann-Lücke, Department of Clinical Biochemistry, Aarhus University Hospital, Norrebrogade 44, 8000 Aarhus C, Denmark, Phone: +45 784 22313, Fax: +45 784 24352

We thank Kirsten Kruse Olsen, Inger Marie Jensen and Anna Lisa Christensen for excellent technical assistance.

Conflict of interest statement

Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article. Research support played no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Research funding: This work was supported by the Danish Medical Research Council and the Lundbeck Foundation.

Employment or leadership: None declared.

Honorarium: None declared.


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Received: 2012-8-29
Accepted: 2012-10-23
Published Online: 2012-11-23
Published in Print: 2013-03-01

©2013 by Walter de Gruyter Berlin Boston

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